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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.
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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.
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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.
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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.
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Female , Humans , Pregnancy , Blood Glucose/metabolism , Diabetes, Gestational/metabolism , Glucose/metabolism , Melatonin/metabolism , Polymorphism, Genetic , PPAR gamma , Receptor, Melatonin, MT2/geneticsABSTRACT
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.
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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.
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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.
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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.
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OBJECTIVE@#To investigate the cardioprotective effect of Danqi Tablet (DQT, ) on ischemic heart model rats and the regulative effect on energy metabolism through peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α).@*METHODS@#Rat ischemic heart model was induced by ligation of left anterior descending coronary artery. Totally 40 Sprague-Dawley rats were randomly divided into sham group, model group, DQT group (1.5 mg/kg daily) and trimetazidine (TMZ) group (6.3 mg/kg daily) according to a random number table, 10 rats in each group. Twenty-eight days after continuous administration, cardiac function was assessed by echocardiography and the structures of myocardial cells were observed by hematoxylin-eosin staining. The level of adenosine triphosphate (ATP) in myocardial cells was measured by ATP assay kit. Expressions level of key transcriptional regulators, including PGC-1α, Sirtuin 1 (SIRT1), AMP-activated protein kinase (AMPK), and downstream targets of PGC-1α, such as mitofusin 1 (MFN1), mitofusin 2 (MFN2) and superoxide dismutase 2 (SOD2) were measured by Western blot. Expression level of PGC-1α was examined by immunohistochemical staining.@*RESULTS@#The rat ischemic heart model was successfully induced and the heart function in model group was compromised. Compared with the model group, DQT exerted cardioprotective effects, up-regulated the ATP production in myocardial cells and inhibited the infiltration of inflammatory cells in the margin area of infarction of the myocardial tissues (P<0.01). The expressions of PGC-1α, SIRT1 and AMPK were increased in the DQT group (all P<0.05). Furthermore, the downstream targets, including MFN1, MFN2 and SOD2 were up-regulated (P<0.05 or P<0.01). Compared with the TMZ group, the expression levels of PGC-1α, MFN1 and SOD2 were increased by DQT treatment (P<0.05 or P<0.01).@*CONCLUSION@#DQT regulated energy metabolism in rats with ischemic heart model through AMPK/SIRT1 -PGC-1α pathway. PGC-1α might serve as a promising target in the treatment of ischemic heart disease.
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OBJECTIVE@#To investigate the protective effect of electroacupuncture (EA) at "Zusanli" (ST 36) in pregnant rats on lung dysplasia of newborn rats with intrauterine growth restriction (IUGR) induced by maternal food restriction.@*METHODS@#Twenty-four female SD rats were randomly divided into a control group, a control+EA group, a model group and a model+EA group, 6 rats in each group. From the 10th day into pregnancy to the time of delivery, the rats in the model group and the model+EA group were given with 50% dietary restriction to prepare IUGR model. From the 10th day into pregnancy to the time of delivery, the rats in the control+EA group and the model+EA group were treated with EA at bilateral "Zusanli" (ST 36), once a day. The body weight of offspring rats was measured at birth, and the body weight and lung weight of offspring rats were measured on the 21st day after birth. The lung function was measured by small animal lung function detection system; the lung tissue morphology was observed by HE staining; the content of peroxisome proliferator activated receptor γ (PPARγ) in lung tissue was detected by ELISA.@*RESULTS@#Compared with the control group, the body weight at birth as well as the body weight, lung weight, lung dynamic compliance (Cdyn) and PPARγ at 21 days after birth in the model group were significantly decreased (@*CONCLUSION@#EA at "Zusanli" (ST 36) may protect the lung function and lung histomorphology changes by regulating the level of PPARγ of lung in IUGR rats induced by maternal food restriction.
Subject(s)
Animals , Female , Pregnancy , Rats , Acupuncture Points , Electroacupuncture , Fetal Growth Retardation/therapy , Lung , Rats, Sprague-DawleyABSTRACT
Thiazolidinediones (TZDs) are currently the only recognized insulin sensitizers available for the clinical treatment of type 2 diabetes. Although their advantages are recognized, the profiles of numerous adverse effects hinder the continued use of these drugs. Peroxisome proliferator-activated receptor γ (PPARγ) is known as a receptor for TZDs, and its underlying mechanisms of pharmacological actions and adverse effects have been deeply explored. To maximally preserve the PPARγ-mediated insulin sensitizing effects and reduce the occurrence of related adverse effects, the concept of "selective PPARγ modulators (SPPARMs)" has been proposed and developed, guiding the development of new drugs. In this review, we summarize the recent research progress in the definition of SPPARMs, the candidate classification and the molecular underpinnings, as well as present the discovery of the YR series compounds as an example, and discuss the potential application prospects of SPPARMs.
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OBJECTIVES@#To investigate the effect of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) on liver injury induced by periodontitis in rats.@*METHODS@#Twenty-four male Wistar rats were randomly divided into two groups: control group and periodontitis group, twelve per group. In periodontitis group, the periodontitis models were established for the maxillary first molars in rats by means of "wire ligation+vaccinationwith @*RESULTS@#The probing depth, tooth mobility and sulcus bleeding index in periodontitis group were significantly higher than that in control group. HE staining showed in periodontitis group, hepatic cords ranged disorderly and there were vacuoles in cells and inflammatory cells infiltrated in liver tissues of rats, and there was no obvious abnormality in control group. The qRT-PCR results showed that the mRNA expression levels of @*CONCLUSIONS@#PGC-1α may be involved in the process of periodontitis-induced liver injury in rats.
Subject(s)
Animals , Male , Rats , Liver/injuries , PPAR gamma , Periodontitis/pathology , Rats, WistarABSTRACT
OBJECTIVE@#This research is to investigate the antihyperglycaemic activity and the underlying mechanisms of action of the ethylacetate extract of Chlorophytum alismifolium (EACA) tubers in a type 2 diabetes model.@*METHODS@#The tubers were processed and sequentially extracted in hexane followed by ethylacetate, using a Soxhlet apparatus, and subjected to gas chromatography-mass spectrometry (GC-MS). The acute toxicity of EACA was investigated in albino Wistar rats. An antihyperglycaemic study was carried out using high-fat diet (pelletized diet and margarine in the ratio of 10:1 and 20% fructose solution) and streptozotocin-induced hyperglycaemic Wistar rats. The effects of the extract (150, 300 and 600 mg/kg) on blood glucose level, insulin, peroxisome proliferator-activated receptor-γ (PPAR-γ) and dipeptidyl peptidase-4 (DPP-4) were evaluated using enzyme-linked immunosorbent assay.@*RESULTS@#The oral median lethal dose in Wistar rats was estimated to be > 5000 mg/kg. Treatment with EACA at all doses significantly reduced the fasting blood glucose levels, compared to the hyperglycaemic control, and over time. Administration of EACA increased the serum insulin and PPAR-γ levels while decreasing DPP-4 levels. GC-MS analysis revealed the presence of 13 compounds, with isothiazole and isoxazolidine covering total area of 24.6% and 22.69%, respectively.@*CONCLUSION@#The findings from this study showed that EACA has important compounds with beneficial effect in type 2 diabetes and acts by increasing insulin secretion and PPAR-γ level and decreasing DPP-4 activity.
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Disulfide-bond A oxidoreductase-like protein (DsbA-L) is a molecular chaperone involved in the multimerization of adiponectin. Recent studies have found that DsbA-L is related to metabolic diseases including gestational diabetes mellitus (GDM), and can be regulated by peroxisome proliferator-activated receptor γ (PPARγ) agonists; the specific mechanism, however, is uncertain. Furthermore, the relationship between DsbA-L and the novel adipokine chemerin is also unclear. This article aims to investigate the role of DsbA-L in the improvement of insulin resistance by PPARγ agonists in trophoblast cells cultured by the high-glucose simulation of GDM placenta. Immunohistochemistry and western blot were used to detect differences between GDM patients and normal pregnant women in DsbA-L expression in the adipose tissue. The western blot technique was performed to verify the relationship between PPARγ agonists and DsbA-L, and to explore changes in key molecules of the insulin signaling pathway, as well as the effect of chemerin on DsbA-L. Results showed that DsbA-L was significantly downregulated in the adipose tissue of GDM patients. Both PPARγ agonists and chemerin could upregulate the level of DsbA-L. Silencing DsbA-L affected the function of rosiglitazone to promote the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (PKB)/AKT pathway. Therefore, it is plausible to speculate that DsbA-L is essential in the environment of PPARγ agonists for raising insulin sensitivity. Overall, we further clarified the mechanism by which PPARγ agonists improve insulin resistance.
ABSTRACT
Disulfide-bond A oxidoreductase-like protein (DsbA-L) is a molecular chaperone involved in the multimerization of adiponectin. Recent studies have found that DsbA-L is related to metabolic diseases including gestational diabetes mellitus (GDM), and can be regulated by peroxisome proliferator-activated receptor γ (PPARγ) agonists; the specific mechanism, however, is uncertain. Furthermore, the relationship between DsbA-L and the novel adipokine chemerin is also unclear. This article aims to investigate the role of DsbA-L in the improvement of insulin resistance by PPARγ agonists in trophoblast cells cultured by the high-glucose simulation of GDM placenta. Immunohistochemistry and western blot were used to detect differences between GDM patients and normal pregnant women in DsbA-L expression in the adipose tissue. The western blot technique was performed to verify the relationship between PPARγ agonists and DsbA-L, and to explore changes in key molecules of the insulin signaling pathway, as well as the effect of chemerin on DsbA-L. Results showed that DsbA-L was significantly downregulated in the adipose tissue of GDM patients. Both PPARγ agonists and chemerin could upregulate the level of DsbA-L. Silencing DsbA-L affected the function of rosiglitazone to promote the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (PKB)/AKT pathway. Therefore, it is plausible to speculate that DsbA-L is essential in the environment of PPARγ agonists for raising insulin sensitivity. Overall, we further clarified the mechanism by which PPARγ agonists improve insulin resistance.
ABSTRACT
Objective: To explore the expression levels of miR-23a-3p and miR-27a-3p in the sera of mice with ulcerative colitis (UC) and their potential action mechanisms. Methods: Twenty C57BL/6 mice were randomly divided into the control group and the model group with 10 mice in each group. The model group mice were induced orally by water with 5% dextran sulfate sodium (DSS) for 7 d. During the induction period, the general condition, fecal morphology and occult blood status of the mice were observed. After 7 d, the whole blood and colon tissues of mice were collected, and the colon lengths and wet weights were measured. The expressions of miR-23a-3p and miR-27a-3p in the sera were detected by qRT-PCR. The expressions of peroxisome proliferator-activated receptor γ, coactivator-1α (PPARGC1A), PH domain leucine-rich repeat protein phosphatase 2 (PHLPP2), B-cell lymphoma-2 (BCL-2), BCL-2 associated X protein (BAX), cytochrome c (CYT-C) and cleaved cysteine-containing aspartate-specific protease (cleaved-caspase-3) were detected by Western blotting. Results: After DSS induction, the model group mice showed mental depression, weight loss, diarrhea, and bloody stool, whose colon lengths were shortened and colon wet weights decreased. The UC model was constructed successfully. In the model group, the expressions of miR-23a-3p and miR-27a-3p in the sera decreased significantly (P<0.05), and the expressions of PPARGC1A, PHLPP2, BAX, CYT-C and cleavedcaspase- 3 in the colon tissues increased significantly (P<0.05), but BCL-2 decreased (P<0.05). Conclusion: The expressions of miR-23a-3p and miR- 27a-3p are low in the sera of UC mice, which may be involved in the occurrence and development of UC by up regulating the expressions of PPARGC1A and PHLPP2 in the colons and triggering mitochondrial pathway to induce apoptosis.
ABSTRACT
OBJECTIVE: To observe the effect of eletroacupuncture (EA) intervention on lipid metabolism and expression of AMP-activated kinase (AMPK), p38 mitogen-activated protein kinase (p38 MAPK) and peroxisome proliferator-activated receptor γ (PPARγ) protein in the liver in rats with insulin resistance (IR), so as to reveal its mechanisms underlying improvement of IR. METHODS: Forty male SD rats were randomly divided into blank control, model, medication, and EA groups (n＝8 in each). The IR model was established by feeding the rats with high-fat diet for 12 weeks. After successful establishment of model, the rats in the blank control group and model group were fixed in the self-made rat bag without receiving any treatment. The rats in the medication group were treated by gavage of pioglitazone (10 mL/kg). EA (2 Hz /100 Hz, 1 mA) was applied to bilateral "Fenglong"(ST40) and "Sanyinjiao"(SP6) for 20 min, once a day, for continuous 14 days for rats in the EA group. The ultrastructure of the liver tissue was observed by transmission electron microscope (TEM). Blood samples were taken from the abdominal aorta for detecting serum C-peptide (C-P), adiponectin (ADP), leptin (LEP) and resistin (RES) contents using enzyme linked immunosorbent assay (ELISA). The expression levels of AMPK, p38 MAPK and PPARγ proteins in the liver tissue were detected by Western blot. RESULTS: After modeling, the contents of serum C-P, LEP and RES, and the expression of liver p38 MAPK protein were significantly up-regulated (P0.05). Outcomes of TEM showed that morphological structure of liver mitochondria was damaged, including a large number of lipid droplets, being blur in appearance, rupture of partial membrane, dissapearance of partial mitochondrial crests with vacuolus-like appearance and decrease of rough endoplasmic reticulum in the model group, which was relatively milder in both EA and medication groups. CONCLUSION: EA intervention is able to improve the disorder of lipid metabolism of IR rats, which may be associated with its effects in lowering the activity of fatty acid synthesis-related enzymes and regulating AMPK/p38 MAPK/PPARγ signaling to improve IR in the liver tissue.
ABSTRACT
Objective: To observe the effect of diosgenin on aplastic anemia (AA) mice and peroxisome proliferator activated receptor γ (PPARγ), CCAAT-enhancer binding protein α (C/EBPα), Adiponectin, Leptin, in order to discuss the potential mechanism of bone marrow mesenchymal stem cells in the process of adipemia. Method: BALB/c mice were randomly divided into control group and model group. The model group was established by 60Coy irradiation combined with tail vein infusion with lymphatic suspension cells of DBA/2 mice. After successful evaluation of the model, the mice were randomly divided into 6 groups:model group, low, medium and high-dose diosgenin groups (37.44,74.88,149.76 mg·kg-1·d-1), cyclosporine group (23.5 mg·kg-1·d-1), and tripterygium glycoside group (9.36 mg·kg-1·d-1), and given corresponding drugs by gavage for 14 days. After the intervention, the peripheral blood of mice in each group was detected, and bone marrow smears were collected to evaluate the proliferation of bone marrow. Bone marrow mesenchymal stem cells (BMMSCs) were isolated and cultured by adherent method and induced by adipogenesis. The mRNA and protein expressions of PPARγ, C/EBPα, Adiponectin, Leptin in BMMSCs were detected by quantitative real-time fluorescent quantitative polymerase chain reaction(Real-time PCR) and Western blot. Result: The white blood cell (WBC), hemoglobin (HGB) and blood platelet (PLT) in peripheral blood of model group were significantly lower than those of normal group (PPγ, C/EBPα, Adiponectin and Leptin in BMMSCs of the model group increased significantly (Pγ, C/EBPα, Adiponectin and Leptin in the middle-dose group diosgenin decreased obviously, which was better than those of Tripterygium glycoside group (P0.05). Conclusion: Diosgenin can promote the recovery of peripheral blood in aplastic anemia mice and improve the hematopoiesis of bone marrow. Diosgenin can reduce the expressions of PPARγ and C/EBPα, the formation of adipocytes and the secretion of Adiponectin and Leptin in adipocytes, and effectively inhibit the process of adipose tissue derived from bone BMMSCs.
ABSTRACT
Objective: To explore the protective effect of formula of Gougancai decoction (FGD) on acute liver injury induced by carbon tetrachloride (CCl4) in rats, in order to provide basis for the development of pharmaceutical preparations or healthcare products. Method: Sixty rats were randomly divided into normal group, Silymarin group (120 mg·kg-1) and FGD groups (475, 950, 1 900 mg·kg-1). The normal group and the model group were given equal volume of saline by gavage, while the other groups were administered with the corresponding dose of drugs according to the body weight. After 10 days, the acute liver injury model was established with 12% carbon tetrachloride peanut oil solution (5 mL·kg-1), except the normal group. All of the rats were put to death to collect serum and liver tissues. The contents of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin (TBIL), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were detected by biochemical methods, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in liver tissues were determined by enzyme-linked immunosorbnent assay(ELISA). Nuclear factor-κB (NF-κB) and peroxisome proliferator-activated receptor-γ (PPAR-γ) protein expression in liver tissues were detected by Western blot, and htoxylin eosin (HE) staining was used to observe the variation of liver histopathological. Result: Compared with the normal group, the serum activities of AST, ALT, ALP and the content of TBIL, MDA in the model group were significantly increased (Pα, IL-1β, IL-6 in liver tissue were remarkably increased (PPκB was enhanced in liver tissue (Pγ was down-regulated (PPPα, IL-1β, IL-6 (PPκB (PPγ (PPConclusion: FGD has a protective effect on CCl4-induced acute liver injury in rats, and its mechanism may be related to the activation of PPAR-γ and the inhibition of NF-κB signaling pathway, with anti-inflammatory and anti-oxidative effects.
ABSTRACT
OBJECTIVE： To investigate the effects of total flavonoids from Psidium guajava leaves （GLTF） on the related factors for estrogen-associated receptor γ（ERRγ）/cyclic adenosine monophosphate responsive element binding protein H（CREBH）pathway in liver of type 2 diabetes mellitus（T2DM）model mice， and to investigate the specific mechanism of its hypoglycemic effect. METHODS： Healthy male ICR mice were collected. T2DM models were established by high-sugar and high-fat diet feeding combined with repeated intraperitoneal injection of low dose streptozotocin. According to the blood glucose value， model mice were randomly divided into model group， metformin group（positive control， 0.17 g/kg），Xiaoke jiangtang capsule group（positive control， 0.75 g/kg），GLTF low-dose and high-dose groups（0.047， 0.094 g/kg）， with 12 mice in each group. Another 12 normal mice were included in normal group. Except that normal group and model group were given constant volume of water intragastrically， other groups were given relevant solution 10 mL/kg intragastrically， qd， for consecutive 21 d. After administration， fasting blood glucose and serum insulin levels of mice were measured and insulin sensitivity index （ISI） was calculated. Histopathological changes of liver and pancreas were observed by HE staining. The protein expressions of ERRγ and CREBH in liver tissues were detected by immunoblotting. The mRNA expression of peroxisome proliferator-activated receptor-γ coactivator-1α（PGC1α）and CREB protein co-activator 2（TORC2）in liver tissue of mice were measured by RT-PCR. RESULTS： Compared with normal group， the levels of fasting blood glucose and serum insulin in T2DM mice were significantly increased in model group， while ISI was decreased significantly （P＜0.01）. The pathological changes of liver tissue were obvious and a large number of vacuoles could be seen. The number and volume of islets in pancreatic tissue decreased， and islet cells showed mild vacuolar lesions. The protein expression of ERRγ and CREBH， mRNA expression of PGC1α and TORC2 in liver tissue were increased significantly （P＜0.01）. Compared with model group， above blood glucose， insulin indexes and pathological changes were improved significantly in GLTF groups. Protein expression of ERRγ and CREBH， mRNA expression of PGC1α and TORC2 in liver tissue were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： GLTF showed obvious hypoglycemic effect on T2DM model mice； its mechanism might be related to inhibiting ERRγ/CREBH signaling pathway.