Upregulation of PGC-1α expression by pioglitazone mediates prevention of sepsis-induced acute lung injury

Abstract The imbalance between pro-inflammatory M1 and anti-inflammatory M2 macrophages plays a critical role in the pathogenesis of sepsis-induced acute lung injury (ALI). Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) may modulate macrophage polarization toward the M2 phenotype by altering mitochondrial activity. This study aimed to investigate the role of the PGC-1α agonist pioglitazone (PGZ) in modulating sepsis-induced ALI. A mouse model of sepsis-induced ALI was established using cecal ligation and puncture (CLP). An in vitro model was created by stimulating MH-S cells with lipopolysaccharide (LPS). qRT-PCR was used to measure mRNA levels of M1 markers iNOS and MHC-II and M2 markers Arg1 and CD206 to evaluate macrophage polarization. Western blotting detected expression of peroxisome proliferator-activated receptor gamma (PPARγ) PGC-1α, and mitochondrial biogenesis proteins NRF1, NRF2, and mtTFA. To assess mitochondrial content and function, reactive oxygen species levels were detected by dihydroethidium staining, and mitochondrial DNA copy number was measured by qRT-PCR. In the CLP-induced ALI mouse model, lung tissues exhibited reduced PGC-1α expression. PGZ treatment rescued PGC-1α expression and alleviated lung injury, as evidenced by decreased lung wet-to-dry weight ratio, pro-inflammatory cytokine secretion (tumor necrosis factor-α, interleukin-1β, interleukin-6), and enhanced M2 macrophage polarization. Mechanistic investigations revealed that PGZ activated the PPARγ/PGC-1α/mitochondrial protection pathway to prevent sepsis-induced ALI by inhibiting M1 macrophage polarization. These results may provide new insights and evidence for developing PGZ as a potential ALI therapy.

Effect and Mechanism of Total Saponins from Panax Japonicus on White Adipose Tissue Browning/Brown Adipose Tissue Activation in High-fat Diet-induced Mice / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of total saponins from Panax japonicus （TSPJ） on white adipose tissue （WAT） browning/brown adipose tissue （BAT） activation in C57BL6/J male mice fed on a high-fat diet （HFD）. MethodThirty-two C57BL6/J male mice （8-week-old） were randomly divided into a normal group， a model group， a low-dose TSPJ group， and a high-dose TSPJ group. The mice in the low-dose and high-dose TSPJ groups were given TSPJ for four months by gavage at 25， 75 mg·kg-1·d-1， respectively， and those in the other groups were given 0.5% sodium carboxymethyl cellulose （CMC-Na） accordingly. After four months of feeding， all mice were placed at 4 ℃ for acute cold exposure， and the core body temperature was monitored. Subsequently， all mice were sacrificed， and BAT and inguinal WAT （iWAT） were separated rapidly to detect the corresponding indexes. Hematoxylin-eosin （HE） staining was used to observe the morphological changes in each group. The effect of TSPJ on the mRNA expression of uncoupling protein 1 （UCP1）， fatty acid-binding protein 4 （FABP4）， cytochrome C （CytC）， PR domain-containing protein 16 （PRDM16）， elongation of very long chain fatty acids protein 3 （ELOVL3）， peroxisome proliferator-activated receptor γ （PPARγ）， and peroxisome proliferator-activated receptor-γ coactivator-1α （PGC-1α） in iWAT and BAT was detected by Real-time polymerase chain reaction （Real-time PCR）. Western blot was also used to detect the protein expression of UCP1， PRDM16， PPARγ， and PGC-1α in BAT and iWAT of each group. The effect of TSPJ on UCP1 expression in BAT and iWAT was detected by immunohistochemistry. Result① Compared with the model group， TSPJ could decrease the body weight and proportions of iWAT and BAT in the HFD-induced mice （P<0.05， P<0.01）. ② The body temperature of mice in the model group decreased compared with that in the normal group in the acute cold exposure tolerance test （P<0.05）. The body temperature in the high-dose TSPJ group increased compared with that in the model group （P<0.01）. ③ Compared with the normal group， the model group showed increased adipocyte diameter in iWAT and BAT and decreased number of adipocytes per unit area. Compared with the model group， the TSPJ groups showed significantly reduced cell diameter and increased number of cells per unit area， especially in the high-dose TSPJ group. ④ Compared with the normal group， the model group showed decreased mRNA expression of FABP4， UCP1， CytC， PRDM16， ELOVL3， PGC-1α， and PPARγ in adipose tissues of mice （P<0.05， P<0.01）. Compared with the model group， after intervention with TSPJ， the mRNA expression was significantly up-regulated （P<0.05， P<0.01）. ⑤ Compared with the normal group， the model group showed decreased protein expression of UCP1， PRDM16， PPARγ， and PGC-1α in adipose tissues of mice （P<0.05， P<0.01）. Compared with the model group， after intervention with TSPJ， the protein expression increased significantly （P<0.05， P<0.01）. ConclusionTSPJ could induce the browning of iWAT/BAT activation and enhance adaptive thermogenesis in obese mice induced by HFD. The underlying mechanism may be attributed to the activation of the PPARγ/PGC-1α signaling pathway.

Gegen Qinliantang Ameliorates Glucose and Lipid Metabolism Disorders in Rat Model of Catch-up Growth by Regulating SIRT1/PGC1α/Nrf1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Gegen Qinliantang on glucose and lipid metabolism in the rat model of catch-up growth （CUG） induced by a high-fat diet and the underlying mechanism. MethodA total of 60 SD rats were randomized into a normal control group （n=18） and a modeling group （n=42）. The rat model of CUG was established with a restricted diet followed by a high-fat diet， and the changes of general status and body weight were observed. The levels of fasting blood glucose （FBG）， fasting insulin （FINS）， triglyceride （TG）， and total cholesterol （TC） were measured in 6 rats in each group at the end of the 4th and 8th week， respectively. The homeostasis model assessment of insulin resistance index （HOMA-IR） was calculated， and the insulin sensitivity and body composition changes of CUG rats were evaluated. The successfully modeled rats were assigned into 6 groups： normal control， model， high-， medium-， and low-dose Gegen Qinliantang （2.5， 5， 10 g·kg-1）， and pioglitazone （3.125 mg·kg-1）. The rats were administrated with corresponding drugs by gavage for 6 weeks， and the normal control group and model group were administrated with the same amount of normal saline. During the experiment period， the changes of body weight were recorded， and the FBG， FINS， HOMA-IR， TG， and TC were determined at the end of the experiment. Hematoxylin-eosin （HE） staining was employed to observe the pathological changes of skeletal muscle in rats. The levels of reactive oxygen species （ROS） and malondialdehyde （MDA） in the skeletal muscle were measured strictly according to the manuals of the reagent kits. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was performed to measure the mRNA levels of silencing information regulator 1 （SIRT1）， peroxisome proliferator-activated receptor-gamma coactivator1α （PGC1α）， and nuclear respiratory factor 1 （Nrf1） in the skeletal muscle. Western blot and immunohistochemistry were employed to assess the expression of SIRT1， PGC1α， and Nrf1 in the skeletal muscle. ResultCompared with the normal control group， the model group presented elevated levels of FBG， FINS， TG， and TC （P<0.05， P<0.01）， increased HOMA-IR （P<0.01）， increased diameter of muscle fibers and adipocytes between muscle cells in the skeletal muscle， rising levels of ROS and MDA in the skeletal muscle （P<0.01）， and down-regulated mRNA and protein levels of SIRT1， PGC1α， and Nrf1 （P<0.05， P<0.01）. Compared with the model group， Gegen Qinliantang （especially the medium and high doses） and pioglitazone decreased the body weight， FINS， HOMA-IR， and TG （P<0.05， P<0.01） and reduced interstitial components such as intermuscular fat in the skeletal muscles and the diameter of muscle fibers. Furthermore， the drugs lowerd the levels of ROS and MDA （P<0.05， P<0.01） and up-regulated the mRNA and protein levels of SIRT1， PGC1α， and Nrf1 （P<0.05， P<0.01） in the skeletal muscle. ConclusionGegen Qinliantang can ameliorate the glucose and lipid metabolism disorders and insulin resistance in CUG rats by regulating the SIRT1/PGC1α/Nrf1 signaling pathway.

Rutin forestalls dysregulated cardiac bioenergetics in bisphenol A and dibutyl phthalate-exposed rats through PPAR? and AMPK modulation

Objectives: Proper cardiac function is greatly dependent on adequate supply and metabolism of energy substrates. Environmental pollutants exposure including plasticizers can trigger adverse cardiac metabolic events. This study was designed to investigate the ameliorative effect of rutin (Rt) on dysregulated cardiac energy metabolism in plasticizer-exposed rats. Materials and Methods: Forty-two rats were randomised into seven groups (n = 6): Control (0.1% dimethyl sulfoxide), bisphenol A (BPA, 25 mg/kg, p.o), dibutyl phthalate (DBP, 25 mg/kg, p.o), BPA + Rt 25 mg/kg, Rt 50 mg/kg, DBP + Rt (25 mg/kg, Rt 50 mg/kg), BPA + DBP and BPA + DBP + Rt, daily for 21 days. Results: BPA and DBP exposure increased plasma glucose, reduced insulin, and increased plasma and cardiac free fatty-acid. Cardiac glucose-6-phosphate level, hexokinase and pyruvate dehydrogenase activities increased in DBP while BPA reduced these variables. Cardiac glucose transporter-4 expression was reduced in BPA group, while cardiac peroxisome proliferator-activated receptor-alpha (PPAR?) and AMP-activated protein kinase (AMPK) expression increased in BPA and DBP-treated rats. However, Rt administration prevents impaired cardiac bioenergetics and glucometabolic regulation. Conclusion: Summarily, Rt improves BPA and DBP-impaired cardiac bioenergetics through PPAR? and AMPK modulation.

Fasudil mediates neuroprotection in ischemia/reperfusion by modulating the ROCK-PPARα-NOX axis

Purpose: Cerebral ischemia-reperfusion (I/R) is a neurovascular disorder that leads to brain injury. In mice, Fasudil improves nerve injury induced by I/R. However, it is unclear if this is mediated by increased peroxisome proliferator-activated receptor-α (PPARα) expression and reduced oxidative damage. This study aimed to investigate the neuroprotective mechanism of action of Fasudil. Methods: MCAO (Middle cerebral artery occlusion) was performed in male C57BL/6J wild-type and PPARα KO mice between September 2021 to April 2023. Mice were treated with Fasudil and saline; 2,3,5-Triphenyltetrazolium chloride (TTC) staining was performed to analyze cerebral infarction. PPARα and Rho-associated protein kinase (ROCK) expression were detected using Western blot, and the expression of NADPH subunit Nox2 mRNA was detected using real-time polymerase chain reaction. The NADPH oxidase activity level and reactive oxygen species (ROS) content were also investigated. Results: After cerebral ischemia, the volume of cerebral necrosis was reduced in wild-type mice treated with Fasudil. The expression of PPARα was increased, while ROCK was decreased. Nox2 mRNA expression, NADPH oxidase activity, and ROS content decreased. There were no significant changes in cerebral necrosis volumes, NADPH oxidase activity, and ROS content in the PPARα KO mice treated with Fasudil. Conclusions: In mice, the neuroprotective effect of Fasudil depends on the expression of PPARα induced by ROCK-PPARα-NOX axis-mediated reduction in ROS and associated oxidative damage.

Role of melatonin receptor 1B gene polymorphism and its effect on the regulation of glucose transport in gestational diabetes mellitus / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Melatonin receptor 1B (MT2, encoded by the MTNR1B gene), a high-affinity receptor for melatonin, is associated with glucose homeostasis including glucose uptake and transport. The rs10830963 variant in the MTNR1B gene is linked to glucose metabolism disorders including gestational diabetes mellitus (GDM); however, the relationship between MT2-mediated melatonin signaling and a high birth weight of GDM infants from maternal glucose abnormality remains poorly understood. This article aims to investigate the relationship between rs10830963 variants and GDM development, as well as the effects of MT2 receptor on glucose uptake and transport in trophoblasts. TaqMan-MGB (minor groove binder) probe quantitative real-time polymerase chain reaction (qPCR) assays were used for rs10930963 genotyping. MT2 expression in the placenta of GDM and normal pregnant women was detected by immunofluorescence, western blot, and qPCR. The relationship between MT2 and glucose transporters (GLUTs) or peroxisome proliferator-activated receptor γ (PPARγ) was established by western blot, and glucose consumption of trophoblasts was measured by a glucose assay kit. The results showed that the genotype and allele frequencies of rs10830963 were significantly different between GDM and normal pregnant women (P<0.05). The fasting, 1-h and 2-h plasma glucose levels of G-allele carriers were significantly higher than those of C-allele carriers (P<0.05). Besides, the protein and messenger RNA (mRNA) expression of MT2 in the placenta of GDM was significantly higher than that of normal pregnant women (P<0.05). Melatonin could stimulate glucose uptake and GLUT4 and PPARγ protein expression in trophoblasts, which could be attenuated by MT2 receptor knockdown. In conclusion, the rs10830963 variant was associated with an increased risk of GDM. The MT2 receptor is essential for melatonin to raise glucose uptake and transport, which may be mediated by PPARγ.

Regulation of PGC1α on SiO2-induced lipid accumulation in macrophages and fibrosis in pulmonary fibroblasts / 环境与职业医学

Background The pathogenesis of silicosis is complex and treatment methods are limited. SiO2-induced increase of transforming growth factor-β1 (TGF-β1) can activate fibroblasts to promote collagen deposition, ultimately leading to fibrosis. Previous studies have confirmed that lipid metabolism plays an important role in the progression of silicosis. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) mediates mitochondrial dysfunction and lipid metabolism pathways in diabetic models, but its role in silicosis has not been elucidated. Objective To investigate the effect of PGC1α on lipid metabolism disorder of macrophages induced by SiO2 and its effect on the progression of silicosis fibrosis. Methods (1) Macrophages were divided into four groups by transfecting and silencing PGC1α and its control sequence in macrophages and followed by SiO2 stimulation: negative control group (transfected with si-NC for 48 h), si-PGC1α group (transfected with si-PGC1α for 48 h), SiO2 stimulation group (stimulated with 50 μg·mL−1 SiO2 for 36 h after transfection with si-NC for 48 h), and si-PGC1α+SiO2 group (stimulated with 50 μg·mL−1 SiO2 for 36 h after transfection with si-PGC1α for 48 h). Western blot and cell immunofluorescence were used to test PGC1α expression, 4,4-difluoro-1,3,5,7,8-pentamethyl-4-bora-3a,4a-diaza-s-indacene (BODIPY 493/503) and total cholesterol (TC) and free cholesterol (FC) kits were used to test lipid accumulation, and the Oroboros2k-Oxygraph respiratory test system (O2K) was used to assess the effects of PGC1α on mitochondrial respiratory chain. ELISA kits were used to test TGF-β1 expressed in the macrophage supernatant. (2) Lung fibroblasts were divided into the same four groups as above, and stimulated with the supernatant of macrophages in the above groups. The expression of collagen Ι (COL Ι), E-cadherin (Eca), and fibronectin (FN) were detected by cell immunofluorescence and Western blot to further evaluate the effect of silencing PGC1α on fibrosis. Results The protein expression level of PGC1α stimulated by SiO2 was decreased, and the relative expression level of PGC1α was 0.78 times that of the control group (P<0.05). After transfection with si-PGC1α, the expression of PGC1α was decreased, and the relative protein expression level of the si-PGC1α group was 0.86 times that of the control group (P<0.05). Compared with the SiO2 stimulation group, the staining area of BODIPY 493/503 in the si-PGC1α+SiO2 group was enhanced, and the cholesterol-related indexes [TC, FC and cholesterol ester (CE)] were increased to 1.38, 1.10, and 2.26 times those in the SiO2 stimulation group (P<0.05). The activity of mitochondrial complex Ι was decreased, and the level of complex Ι in the si-PGC1α+SiO2 group was 0.63 times that in the SiO2 stimulation group (P<0.05). The secretion of TGF-β1 by macrophages increased, and the level of TGF-β1 in the si-PGC1α+SiO2 group was 1.15 times that of the SiO2 stimulation group (P<0.05). In addition, after stimulation of primary lung fibroblasts with macrophage supernatant, silencing PGC1α increased the expression levels of COL Ι and FN, while decreased the expression of Eca. The protein levels of COL Ι, FN, and Eca in the si-PGC1α+SiO2 group were 1.39, 1.18, and 0.82 times those in the SiO2 stimulation group, respectively (P<0.05). Conclusion Silencing PGC1α exacerbates SiO2-induced lipid metabolism disorder, inhibits mitochondrial respiratory chain, and aggravates the fibrosis induced by SiO2, suggesting that PGC1α may participate silicosis fibrosis by regulating mitochondrial respiratory chain and lipid metabolic disorder induced by SiO2.

Icariin Ameliorates Efferocytosis Dysfunction of Alveolar Macrophages Stimulated by Cigarette Smoke Extract via PPARγ Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the mechanism of icariin in ameliorating efferocytosis dysfunction and inflammatory response of alveolar macrophages induced by cigarette smoke extract via the peroxisome proliferator-activated receptor gamma （PPARγ） signaling pathway. MethodThe untreated rat alveolar macrophages （NR8383） were taken as the blank group. The NR8383 cells treated with 10% cigarette smoke extract were divided into model， low-， medium-， and high-dose （10， 20， 40 μmol·L-1） icariin， PPARγ inhibitor， and PPARγ inhibitor + low-， medium-， and high-dose icariin groups. Alamar blue colorimetry was employed to examine the proliferation and toxicity of icariin on NR8383 cells. The efferocytosis rate of NR8383 cells was detected by flow cytometry. Enzyme-linked immunosorbent assay was employed to measure the levels of tumor necrosis factor-alpha （TNF-α）， transforming growth factor-β1 （TGF-β1）， and milk fat globule-epidermal growth factor 8 （MFG-E8）. Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） were employed to determine the protein and mRNA levels， respectively， of PPARγ， CD36， and RAS-related C3 botulinum toxin substrate 1 （Rac1）. ResultThe efferocytosis dysfunction model of NR8383 was established with the cigarette smoke extract. Compared with the blank control group， the model group showed decreased efferocytosis rate （P<0.05）， elevated TNF-α level （P<0.05）， lowered TGF-β1 and MFG-E8 levels （P<0.01）， and down-regulated mRNA and protein levels of PPARγ， CD36， and Rac1 （P<0.05， P<0.01）. Compared with the model group， the treatment with icariin increased the efferocytosis rate （P<0.05， P<0.01）， lowered the TNF-α level （P<0.01）， elevated TGF-β1 and MFG-E8 levels （P<0.05）， and up-regulated the protein and mRNA levels of PPARγ， CD36， and Rac1 （P<0.05， P<0.01）. Compared with icariin alone， PPARγ inhibitor + icariin decreased the efferocytosis rate （P<0.05） and down-regulated the protein and mRNA levels of PPARγ （P<0.05， P<0.01）. In addition， PPARγ inhibitor + low-dose icariin down-regulated the protein level of CD36 （P<0.01） and PPARγ inhibitor + low-/medium-dose icariin up-regulated the protein level of Rac1 （P<0.05）. ConclusionIcariin ameliorates the cigarette smoke extract-induced efferocytosis dysfunction of alveolar macrophage by regulating the PPARγ signaling pathway and cytoskeletal structure rearrangement.

Effects of β-sitosterol on the function of synovial fibroblasts in rheumatoid arthritis and its mechanism / 中国药房

OBJECTIVE To investigate the effects of β-sitosterol on the function of rheumatoid arthritis （RA） fibroblastic synoviocytes MH7A cells and its mechanism. METHODS Network pharmacology was adopted to screen the targets of β-sitosterol and the targets for the treatment of RA. After the intersection of them， topological analysis was performed to find the most critical target in the treatment of RA. MH7A cells were treated with different concentrations （0， 5， 10， 20， 40 μmol/L） of β-sitosterol， and CCK-8 was used to assay cell viability for screening the optimal concentration of β-sitosterol. MH7A cells were induced by 10 ng/mL TNF-α in vitro and treated with β-sitosterol （the optimum concentration）. CCK-8 and EdU were used to detect the ability of cell proliferation. Scratch experiment and Transwell invasion assay were used to analyze cell migration and invasion. The levels of interleukin-1β （IL-1β） and IL-6 in cell supernatant were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expressions of peroxisome proliferator-activated receptor α （PPARα） were measured by qRT-PCR and Western blot， respectively. The siRNA targeting PPARα was transfected into MH7A cells， and the effects of β-sitosterol on cell proliferation， migration， invasion， the secretion of inflammatory factors and the expression of PPARα after PPARα knockdown were detected by the above experimental methods. RESULTS PPARα was the most critical target of β-sitosterol in the treatment of RA. The optimal concentration of β-sitosterol was 20 μmol/L. Compared with model group， β-sitosterol decreased the viability of MH7A cells， and the number of proliferating cells also decreased significantly （P＜0.05）； the cell migration rate and the number of cell invasion decreased significantly （P＜0.05）. The levels of IL-1β and IL-6 were also significantly decreased （P＜0.05）， and the mRNA 15 and protein expression levels of PPARα were significantly increased （P＜0.05）. Compared with negative control small interfering RNA group， after PPARα knockdown， the cell viability increased by about 35.6% （P＜0.05）， the number of cell proliferation， the cell migration rate and the number of cell invasion increased significantly （P＜0.05）， and the levels of IL-1β and IL-6 also increased significantly （P＜0.05）. CONCLUSIONS β-sitosterol could effectively inhibit the proliferation， migration， invasion and secretion of inflammatory factors in MH7A cells， the mechanism of which may be associated with activating PPARα pathway.

Early diagnosis value of peripheral blood PPARγ combined with IFN-γ detection for tuberculosis infection in patients with end-stage renal disease / 中国热带医学

@#Abstract: Objective　To explore the early diagnostic value of peripheral blood peroxisome proliferator-activated receptor γ (PPARγ) combined with γ-interferon (IFN-γ) release assay (IGRA) in the diagnosis of pulmonary tuberculosis in patients with end-stage renal disease (ESRD), and to provide reference for clinical diagnosis and treatment. Methods　From January 2019 to December 2021, 70 ESRD patients with suspicious symptoms of pulmonary tuberculosis were treated at Hebei Chest Hospital were selected as the research objects. According to the examination results, they were divided into ESRD group (40 cases) and ESRD complicated by pulmonary tuberculosis (40 cases, comorbidity group). In addition, 40 cases with pulmonary tuberculosis were used as the PTB group. All three groups of patients underwent IGRA test, and the peripheral blood PPARγ level was detected by enzyme-linked immunosorbent assay, and the diagnostic value of PPARγ combined with IGRA test for ESRD patients with pulmonary tuberculosis was explored. Results The expression level of PPARγ and IFN-γ content in the PTB group and the comorbidity group were obviously higher than those in the ESRD group (P<0.05), while the differences in PPARγ expression level and IFN-γ content between the PTB and comorbidity groups were not statistically significant (P>0.05). The ROC curve showed that the areas under the curve (AUC) of PPARγ and IGRA in the diagnosis of end-stage renal disease combined with tuberculosis were 0.823 (95%CI: 0.722-0.925) and 0.773 (95%CI: 0.662-0.883), respectively, and the AUC of combined detection was 0.928 (95%CI: 0.871-0.984), which was better than that of PPARγ and IGRA alone (Z/P=2.057/0.039, 2.843/0.005). The Kappa values of serum PPARγ and IGRA test compared with the clinical gold standard results in the diagnosis of ESRD complicated with pulmonary tuberculosis were 0.557 and 0.444 (P<0.05). The combined screening of ESRD with pulmonary tuberculosis was consistent with the clinical gold standard (Kappa=0.661, P<0.05). Among the 30 ESRD patients complicated with pulmonary tuberculosis, the sensitivity of PPARγ combined with IGRA test in diagnosis of ESRD complicated with pulmonary tuberculosis was 93.33% (28/30), which was higher than 70.00% (21/30) of PPARγ and 66.67% (20/30) of IGRA test alone (P<0.05). Conclusions Peripheral blood PPARγ and IGRA tests have certain diagnostic value for ESRD complicated with tuberculosis, and the combined detection of the two can improve the sensitivity and reduce the rate of missed diagnosis, which is worthy of clinical promotion.

Research Progress of Active Components of Traditional Chinese Medicine in Treatment of Hyperlipidemia by Activating PPARα Pathway / 中国实验方剂学杂志

Hyperlipidemia is a dyslipidemia caused by dyslipidemia of lipid metabolism， which can be divided into primary and secondary types. The current clinical diagnostic criteria are mainly changes in lipid levels， which are the inducers of high-risk cardiovascular diseases such as atherosclerosis， pancreatitis and coronary heart disease. As a key target in lipid metabolism， peroxisome proliferator-activated receptor α （PPARα） is involved in a variety of metabolic activities， including fatty acid degradation， synthesis， transport， storage， lipoprotein metabolism， etc. Activation of PPARα can maintain the balance of lipid metabolism through a variety of ways， which is an important way to treat hyperlipidemia. At present， chemical drugs such as statins and bettes are mainly used in the clinical treatment of hyperlipidemia. Although they can slow down the disease to a certain extent， there are many adverse reactions and drug resistance. By reviewing the literature in recent years， the author found that the activation of PPARα pathway by traditional Chinese medicine in the treatment of hyperlipidemia has significant effect and small adverse reactions. The lipid-lowering active ingredients include flavonoids， alkaloids， phenols， terpenoids and other compounds. These active components mainly affect the expression of downstream effectors through the activation of PPARα pathway， thereby inhibiting the synthesis of total cholesterol and promoting fatty acid oxidation， and play a role in the treatment of hyperlipidemia. In this paper， we systematically reviewed the structure types and mechanism of active components of traditional Chinese medicine that activate PPARα pathway， so as to provide guidance for the rational development and clinical application of lipid-lowering traditional Chinese medicine new drugs.

Mechanism of Salvianolate in Inducing Autophagy in Podocytes of Rats with Membranous Nephropathy via AMPK/SIRT1/PGC-1α Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of salvianolate on the protein expressions of adenosine monophosphate （AMP）-activated protein kinase （AMPK）， silent information regulator 1 （SIRT1） and peroxisome proliferator-activated receptor-γ coactivator-1α （PGC-1α）， autophagy and apoptosis in kidney tissue of rats with membranous nephropathy （MN）， and to explore its possible molecular mechanism against MN. MethodEighty male SD rats were randomly divided into normal group， model group， benazepril hydrochloride group （10 mg·kg-1）， and salvianolate low-， medium-， and high-dose groups （16.7， 33.3 and 66.7 mg·kg-1）. The rats were modeled by injection of cationized bovine serum albumin （C-BSA） into the tail vein. After successful modeling， rats in the administration groups were given corresponding doses of drugs for 4 consecutive weeks， and then 24-hour urine， serum and kidney tissue were collected for the detection of 24-hour urinary protein （UTP）， blood urea nitrogen （BUN）， serum creatinine （SCr）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， C reactive protein （CRP）， glutathione peroxidase （GSH-Px）， superoxide dismutase （SOD）， and malondialdehyde （MDA）. The pathological changes of kidneys were observed by light microscope， electron microscope and immunofluorescence. Western blot was used to detect the protein expressions of phospho-AMPK （p-AMPK）， AMPK， phospho-SIRT1 （p-SIRT1）， SIRT1 and PGC-1α in rat kidney tissue. The protein expressions of autophagy-specific gene （Beclin-1）， microtubule-associated protein 1 light chain 3 （LC3） Ⅱ， ubiquitin-binding protein （p62）， B cell lymphoma （Bcl-2）， Bcl-2-associated X （Bax）， and cysteine aspartic protease-7 （Caspase-7） in rat kidney tissue were determined by immunohistochemistry （IHC）. ResultCompared with the conditions in the normal group， the levels of UTP， IL-6， TNF-α， CRP and MDA in the model group were increased （P<0.05） while the levels of SOD and GSH-Px were decreased （P<0.05）， and there was no difference in BUN and SCr. Compared with the model group， the administration groups had lowered UTP， IL-6， TNF-α， CRP and MDA （P<0.05） while elevated SOD and GSH-Px （P<0.05）. It could be seen from hematoxylin and eosin （HE） staining， Masson staining， immunofluorescence and electron microscopy that the pathological damage of rat kidney tissue in the model group was significant， but after treatment with benazepril hydrochloride and salvianolate， the pathological damage of kidney cells was gradually improved. The expressions of p-AMPK/AMPK， p-SIRT1/SIRT1， PGC-1α， Bcl-2， Beclin-1 and LC3Ⅱ in rat kidney in the model group were lower than those in the normal group （P<0.05） while the expressions of Bax， Caspase-7 and p62 were higher （P<0.05）. Compared with the model group， benazepril hydrochloride group and salvianolate groups had an up-regulation in the expressions of p-AMPK/AMPK， p-SIRT1/SIRT1， PGC-1α， Bcl-2， Beclin-1 and LC3Ⅱ in the kidney （P<0.05） while a down-regulation in the expressions of Bax， Caspase-7 and p62 （P<0.05）. ConclusionThe protective effect of salvianolate on the kidneys of MN rats may be related to the activation of AMPK/SIRT1/PGC-1α signaling pathway， the up-regulation of autophagy and the reduction of apoptosis.

Efficacy and Safety of Pemafibrate and Bezafibrate in Patients with Type 2 Diabetes / 医薬品情報学

Objective: Management of low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) is important for patients with type 2 diabetes merger hyperlipidemia. Pemafibrate (PF) has different characteristics from conventional fibrates. In this study, we retrospectively compared the efficacy and safety of PF and bezafibrate (BF) in patients with type 2 diabetes merger hypertriglyceridemia.Methods: Patients who were administered PF (0.2 mg/day) or BF (400 mg/day) for 24 weeks or longer were included. Twenty patients in each group were extracted using propensity score matching (PS). PS was calculated using the patient background (before the start of administration) of PF or BF. We investigated lipid-related parameters (TG, high density lipoprotein cholesterol [HDL-C], and LDL-C) and other laboratory test parameters pre administration and 24 weeks post administration.Results: TG decreased significantly in both groups (p<0.05). However, there were no significant differences between the two groups in the TG treatment target (<150 mg/dL) achievement rate (p =1.00), TG change rate (p=0.84), and TG change amount (p=0.77). In addition, there were no significant changes in HDL-C and LDL-C in both groups. In the PF group, alanine transaminase (ALT) (p< 0.05), alkaline phosphatase (p<0.05) decreased. In the BF group, ALT (p<0.05) and γ-GTP (p<0.05) decreased. Both groups showed improvement in liver function after 24 weeks. eGFR (p<0.05) significantly decreased only BF group. There were no significant changes in renal function, creatine kinase (CK), or hemoglobin A1c (HbA1c) in either group.Conclusion: Our study suggests that there is no difference in the TG lowering effect and safety of PF and BF in type 2 diabetic patients.

Research progress of glucocorticoid receptor ligands / 中华实用儿科临床杂志

Glucocorticoids have been applied to clinical treatment of autoimmune diseases and allergic diseases for over 60 years.In recent years, the clinical application of glucocorticoids is annually on the rise with the increased incidence of autoimmune and inflammatory diseases.Therefore, the adverse events of glucocorticoids have been well concerned.It is urgent to analyze the pharmacological mechanism of glucocorticoids, search for novel glucocorticoid receptor ligands with anti-inflammatory and immune inhibitory effects and less adverse events.This study aims to review the research progress of glucocorticoid receptor ligands.

Correlation of serum FABP4 and PPAR γ levels with nonalcoholic fatty liver disease and type 2 diabetes mellitus / 中华内分泌外科杂志

Objective:To explore the correlation between serum adipocyte fatty acid binding protein 4 (FABP4) and peroxisome proliferator activated receptor gamma (PPAR gamma) levels and metabolism related fatty liver disease (MAFLD) and type 2 diabetes mellitus (T2DM) .Methods:230 patients with T2DM and MAFLD in Zhangjiakou First Hospital from Feb. 2019 to Feb. 2021 were selected. According to their disease conditions, 80 patients with T2DM and without MAFLD were set as simple T2DM group, 78 patients with MAFLD and normal glucose tolerance were set as simple MAFLD group, 72 patients with T2DM and MAFLD were set as T2DM and MAFLD group, and 100 healthy volunteers in the same period were selected as the control group.Results:The levels of HOMA-IR and FABP4 in T2DM patients were significantly higher than those in the control group ( P<0.05) , while the levels of HDL-C, crea and PPAR γ in T2DM grou were significantly lower than those in the control group ( P<0.05) . The levels of BMI, AST, alt, GGT, TG, HOMA-IR and FABP4 in MAFLD group were significantly higher than those in control group ( P<0.05) , while the level of PPAR γ in MAFLD group was significantly lower than that in control group ( P<0.05) . BMI, AST, alt, GGT, TG, HOMA-IR and FABP4 of T2DM patients with MAFLD were significantly higher than those of T2DM patients without MAFLD and control group ( P<0.05) , while HDL-C and PPAR γ were significantly lower than those of T2DM patients without MAFLD and control group ( P<0.05) . HOMA-IR and FABP4 in T2DM patients with MAFLD were significantly higher than those in MAFLD group ( P<0.05) , while HDL-C, crea and PPAR γ were significantly lower than those in MAFLD group ( P<0.05) . FABP4 was positively correlated with HOMA-IR and CREA (all P<0.05) , and negatively correlated with HDL-Cand PPAR γ (all P<0.05) . PPAR γ was positively correlated with TG and ALT (all P<0.05) , and negatively correlated with HOMA-IR ( P<0.05) . Alt, TG, HOMA-IR, FABP4 and PPAR γ were independent risk factors for MAFLD in T2DM patients ( P<0.05) . Conclusion:FABP4 is positively correlated with the occurrence of T2DM and MAFLD, PPAR γ is negatively correlated with the occurrence of T2DM and MAFLD, the negative feedback loop regulation of FABP4 and PPAR γ can cause the occurrence of insulin resistance, so as to improve the risk of T2DM combined with MAFLD, and provide clinical basis for clinical disease prevention and treatment.

Remote ischemic preconditioning promotes mitochondrial biosynthesis and protects cerebral ischemia-reperfusion injury in rats via AMPK/PGC-1α signaling pathway / 国际脑血管病杂志

Objective:To investigate the protective mechanism of remote ischemic preconditioning (RIPC) on cerebral ischemia-reperfusion (I/R) injury in rats.Methods:Forty-eight SD rats were randomly divided into sham operation group, RIPC group, I/R group, RIPC+I/R group, and compound C group ( n=9 in each group). The neurological function score, cerebral infarction volume (TCC staining) and neuronal apoptosis rate (TUNEL staining) were measured. The activity of superoxide dismutase (SOD) 2 and malondialdehyde level in homogenate of brain tissue were detected. Expression levels of AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α signaling pathway-related proteins in brain tissue were detected by Western blot. Results:The neurological deficit score, cerebral infarction volume and neuron apoptosis rate in the I/R group were significantly higher than those in the sham operation group (all P<0.05). Compared with the I/R group, the neurological deficit score, cerebral infarction volume and neuron apoptosis rate in the RIPC+I/R group were significantly decreased (all P<0.05). Compared with the RIPC+I/R group, the neurological deficit score, cerebral infarction volume and neuron apoptosis rate in the compound C group were significantly increased (all P<0.05). Compared with the sham operation group, the SOD activity in the I/R group was significantly decreased, and the malondialdehyde content was significantly increased (all P<0.05). Compared with the I/R group, the SOD activity in the RIPC+I/R group was significantly increased, and the malondialdehyde content was significantly decreased (all P<0.05). Compared with the RIPC+I/R group, the SOD activity in the compound C group was significantly decreased, and the malondialdehyde content was significantly increased (all P<0.05). Compared with the sham operation group, the expressions of AMPK, p-AMPK, PGC-1α, nuclear respiratory factor (NRF)-1, mitochondrial transcription factor A (TFAM), SOD2, uncoupling protein 2 (UCP2), cytochrome C (CytC), and apoptosis-inducing factor (AIF) in the brain tissue of the I/R group were significantly increased (all P<0.05). Compared with the I/R group, the expressions of AMPK, p-AMPK, PGC-1α, NRF-1, TFAM, SOD2 and UCP2 in the ischemic brain tissue of the RIPC+I/R group were significantly increased, while the expressions of CytC and AIF were significantly decreased (all P<0.05). Compared with the RIPC+I/R group, the expressions of AMPK, p-AMPK, PGC-1α, NRF-1, TFAM, SOD2 and UCP2 in the brain tissue of the compound C group were significantly decreased, while the expressions of CytC and AIF were significantly increased (all P<0.05). Conclusions:RIPC has a protective effect on I/R injury. Its mechanism may be associated with the activation of AMPK/PGC-1α signaling pathway and maintaining mitochondrial biogenesis.

Study on the relationship between relieving energy crisis in myofascial trigger points with An-Pressing manipulation and AMPK/PGC-1α pathway activation / 针灸推拿医学（英文版）

Objective: To explore the mechanism of An-Pressing manipulation in relieving energy crisis in chronic myofascial trigger points (MTrPs) by observing the effects of An-Pressing manipulation on adenosine triphosphate (ATP), adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) pathway and mitochondrial ultrastructure of skeletal muscle cells in MTrPs rats. Methods: Forty-eight male Sprague-Dawley rats were randomly divided into a blank group, a model group, a lidocaine group, and an An-Pressing manipulation group, with 12 rats in each group. The model group, lidocaine group and An-Pressing manipulation group were used to replicate the MTrPs rat model by blunt shock and centrifugal motion method. After modeling, the An-Pressing manipulation group was subjected to 7 times An-Pressing manipulation, once every other day; the lidocaine group was treated with 3 times of injection of lidocaine at the MTrPs, once every 6 d. The blank group and the model group were fed normally without intervention. After the intervention, local muscle tissue was taken to detect the content of ATP and the expression of AMPK, phosphorylated AMPK (phospho-AMPK), PGC-1α, and glucose transporter 4 (GluT4), and the ultrastructure of mitochondria was observed under an electron microscope. Results: Compared with the blank group, the ATP content in the model group was decreased (P<0.05), the protein expression levels of phospho-AMPK, PGC-1α, and GluT4 and the ratio of phospho-AMPK to AMPK were decreased (P<0.05); under the electron microscope, the number of mitochondria decreased, and they were deformed, small in volume, and had deformed cristae. Compared with the model group, the ATP contents in the An-Pressing manipulation group and the lidocaine group were increased (P<0.05), and the protein expression levels of phospho-AMPK, PGC-1α, and GluT4 and the ratio of phospho-AMPK to AMPK were increased (P<0.05); under the electron microscope, the number of mitochondria increased, the shape and size of the mitochondria were basically normal, and the cristae could be seen. Compared with the lidocaine group, phospho-AMPK and the ratio of phospho-AMPK to AMPK in the An-Pressing manipulation group were increased (P<0.05); under the electron microscope, the numbers of mitochondria were similar, and the shape and size of the mitochondria were basically normal without swelling, and the cristae could be observed. Conclusion: An-Pressing manipulation can increase the ATP content in MTrPs tissue, improve the expression levels of PGC-1α and GluT4 proteins and the ratio of phospho-AMPK to AMPK; its mechanism may relate to the activation of AMPK/PGC-1α signaling pathway to promote the repair of mitochondrial damages.

Effect of Five Huoxue Huayu Prescriptions on Blood Lipid Metabolism， Liver Tissue and ABCA1 and PPARγ Expression in New Zealand Rabbits with Blood Stasis Syndrome / 中国实验方剂学杂志

ObjectiveTo observe the effects of five Huoxue Huayu prescriptions on blood lipid metabolism， liver tissue and adenosine triphosphate binding cassette transporter A1 （ABCA1） and peroxisome proliferator-activated receptor γ（PPARγ） expression in New Zealand rabbits with blood stasis syndrome， and to compare their differences in order to provide laboratory evidence for clinical selection of prescriptions and drugs. MethodSeventy New Zealand rabbits were randomly divided into normal group （n=10） and model group （n=60）. The blood stasis syndrome was modeled by the method of starvation+high-fat feed+adrenaline. After the models were successfully established， they were randomly divided into Xuefu Zhuyutang（3.55 g·kg-1·d-1） group， Danshenyin（1.962 g·kg-1·d-1） group， Shixiaosan（0.56 g·kg-1·d-1） group， Huoluo Xiaolingdan（2.80 g·kg-1·d-1） group， and Taohong Siwutang（2.66 g·kg-1·d-1） group， and were given corresponding compound prescriptions by gavage. The normal group and model group were given the same dose of distilled water. After the treatment of 30 consecutive days， blood was taken from the abdominal aorta to detect the content of total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol（LDL-C） and apolipoprotein A1 （ApoA1）. Hematoxylin-eosin（HE） staining was used to observe the changes in liver tissue. Real-time polymerase chain reaction （Real-time PCR） and Western blot were used to detect the mRNA and protein expression of ABCA1 and PPARγ in liver tissue， respectively. ResultCompared with the conditions in the normal group， increased mRNA and protein levels of HDL-C， LDL-C， TG， TC， and PPARγ （P<0.01）， decreased ApoA1 level （P<0.05） and decreased mRNA and protein levels of ABCA1 （P<0.01） were found in the model group. Compared with the conditions in the model group， the HDL-C level in the five Huoxue Huayu prescriptions was lowered （P<0.05）， and lowered TG level in Xuefu Zhuyutang group and Shixiaosan group （P<0.05）， decreased LDL-C and TC levels in Shixiaosan group （P<0.05）， and increased ApoA1 level in the Huoluo Xiaolingdan group （P<0.01） and Taohong Siwutang group （P<0.05） were observed. Furthermore， the mRNA and protein levels of ABCA1 in Xuefu Zhuyutang group， Shixiaosan group， Huoluo Xiaolingdan group and Taohong Siwutang group were elevated （P<0.05， P<0.01）， and the elevated levels were higher than that of Danshenyin group （P<0.05）. The mRNA level of PPARγ in the five Huoxue Huayu prescriptions was reduced （P<0.01）， and its protein level was also decreased in Xuefu Zhuyutang group， Shixiaosan group， Huoluo Xiaolingdan group and Taohong Siwutang group （P<0.01）. ConclusionThe five Huoxue Huayu prescriptions had a certain therapeutic effect on dyslipidemia，which might be achieved by up-regulating the expression of ApoA1 and ABCA1 to promote the production of HDL-C and strengthen the excretion of dysfunctional HDL-C. And Xuefu Zhuyutang had the optimal effect in lowering lipid.

Protective Effect of Wenxin Prescription on Mitochondrial Energy Metabolism in Rats with Myocardial Ischemia-reperfusion Injury / 中国实验方剂学杂志

ObjectiveTo reveal the effect of Wenxin prescription on mitochondrial energy metabolism and silent information regulator 1 （SIRT1）/peroxisome proliferator-activated receptor-γ coactivator-1α （PGC-1α）/recombinant estrogen-related receptor α （ERRα） signaling pathway in rats with myocardial ischemia-reperfusion injury. MethodTotally 90 male Wistar rats of SPF grade were randomly assigned into a sham operation group， a model group， and low-， medium-， and high-dose Wenxin prescription groups， with 18 rats in each group. The rats in low-， medium-， and high-dose Wenxin prescription groups were administrated with 0.99， 1.98， and 3.96 g·kg-1 granules by gavage， respectively， and those in the sham operation group and model group with the same amount of normal saline. Twenty-one days after pre-administration， the rat model of myocardial ischemia-reperfusion injury was established by ligation of the left anterior descending coronary artery for 30 min and reperfusion for 2 h， and the rats in the sham operation group were only threaded without ligation. Myocardial infarction area was observed through 2，3，5-triphenyl-2h-tetrazolium chloride （TTC） staining， and the myocardial histopathology through hematoxylin-eosin （HE） staining. The levels of creatine kinase-MB （CK-MB） and lactate dehydrogenase （LDH） in serum， cytochrome C oxidase （CCO） and succinate dehydrogenase （SDH） in mitochondrion， and ATP in myocardial tissue were detected according to kit instructions. The mRNA and protein levels of SIRT1， PGC-1α， ERRα， and mitochondrial transcription factor A （TFAM） in myocardial tissue were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the sham operation group， the model group showed broken and disordered myocardial fibers， cytoplasmic edema， and pyknosis and deviation of nuclei. Moreover， the modeling increased the levels of CK-MB and LDH （P<0.05， P<0.01）， lowered the levels of ATP， CCO， and SDH （P<0.05， P<0.01）， and down-regulated the mRNA and protein levels of SIRT1， PGC-1α， ERRα， and TFAM in myocardial tissue （P<0.05， P<0.01）. Compared with the model group， Wenxin prescription reduced the myocardial infarction area （especially in the high-dose group， P<0.01）， restored the pathological changes， lowered the levels of CK-MB and LDH （P<0.05， P<0.01）， increased the levels of ATP， CCO， and SDH （especially in the high-dose group， P<0.01）， and up-regulated the mRNA and protein levels of SIRT1， PGC-1α， ERRα， and TFAM in myocardial tissue （P<0.05， P<0.01）. ConclusionWenxin prescription can protect rats from myocardial ischemia-reperfusion injury by regulating myocardial mitochondrial energy metabolism via the SIRT1/PGC-1α/ERRα signaling pathway.

Isoflavones from Sojae Semen Praeparatum Regulate Lipid Metabolism in Atherosclerotic Mice Through PPARγ/LXRα/ABCA1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo study the effect of isoflavones from Sojae Semen Praeparatum （ISSP） on lipid metabolism in atherosclerotic mice， and decipher the underlying mechanism via the peroxisome proliferator-activated receptor gamma/liver X receptor alpha/ATP-binding cassette transporter A1 （PPARγ/LXRα/ABCA1） signaling pathway. MethodFifty ApoE-/- mice were randomly assigned into the model group， western medicine （atorvastatin calcium， 3.03 mg·kg-1） group， and low-， medium-， and high-dose ISSP （2.5， 5， 10 mg·kg-1， respectively） groups， with 10 rats in each group. Atherosclerosis model mice were established by bilateral ovariectomy and feeding high-fat diet. Another 10 ApoE-/- mice receiving ovariectomy and high-fat diet were taken as the sham group. Some mice died of postoperative infection， and finally 6 mice were included in each group. One week after operation， each group was administrated with corresponding drugs or equivalent amount of normal saline. After 12 weeks， the levels of triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， and non-esterified fatty acids （NEFAs） in serum and liver tissue were measured. The levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in serum were detected by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining and oil red O staining were used for observation of aortic plaque formation and liver lipid deposition. The mRNA and protein levels of PPARγ， LXRα， ABCA1， and ATP-binding cassette transporter G1 （ABCG1） in liver were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultCompared with the sham group， the modeling of atherosclerosis increased the aortic plaque area （P<0.01）， elevated the serum TC， TG， LDL-C， TNF-α， and IL-6 levels （P<0.01）， decreased the level of HDL-C （P<0.01）， increased the liver index （P<0.05） and the levels of TC， TG， and NEFAs in liver （P<0.01）， and caused obvious hepatic fat vacuoles and lipid deposition. In addition， the modeling down-regulated the mRNA levels of PPARγ， LXRα， ABCA1 in liver （P<0.05， P<0.01），and regulated the mRNA and protein levels of ABCG1（P<0.05， P<0.01）. Compared with the model group， atorvastatin calcium and middle-， high-dose ISSP reduced the serum TC， TG， LDL-C， TNF-α， and IL-6 levels （P<0.01）， decreased the liver index （P<0.01）， alleviated the liver fat vacuoles and lipid deposition， and increased the levels of TC， TG， and NEFAs in the liver （P<0.05， P<0.01）. Furthermore， they up-regulated the mRNA and protein levels of PPARγ， LXRα， ABCA1， and ABCG1 in the liver （P<0.05， P<0.01）. ConclusionISSP may regulate lipid metabolism through PPARγ/LXRα/ABCA1 signaling pathway to down-regulate the expression of inflammatory cytokines in serum and alleviate liver lipid deposition， thereby suppressing the formation of atherosclerotic plaque.