Effect of Modified Gegen Qinliantang on FXR/SHP/PPARα Signaling Pathway in Type 2 Diabetic db/db Mice / 中国实验方剂学杂志

ObjectiveTo observe the effect of modified Gegen Qinliantang on the expression levels of proteins related to the farnesoid X receptor/small heterodimer partner/peroxisome proliferator-activated receptor α （FXR/SHP/PPARα） signaling pathway in the liver tissue of db/db model mice with type 2 diabetes mellitus （T2DM） and explore the underlying mechanism of action of modified Gegen Qinliantang. MethodThirty db/db mice were randomly divided into model group， metformin group （0.2 g·kg-1）， and high-， medium-， and low-dose modified Gegen Qinliantang groups （31.9， 19.1， 6.4 g·kg-1）， with 6 mice in each group. An additional six m/m mice were assigned to the blank group. Respective drugs were administered via oral gavage for 12 weeks. Mouse body weight， fasting blood glucose （FBG）， total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） levels were measured. Oil red O staining was used to observe hepatic lipid accumulation and periodic acid-schiff （PAS） staining was used to assess hepatic glycogen deposition. Ammonium ferric sulfate staining was used to observe cholesterol deposition in intestinal tissues. Western blot was employed to detect the expression of FXR， cholesterol 7α-hydroxylase （CYP7A1）， SHP， and PPARα proteins in liver tissues， and enzyme-linked immunosorbent assay （ELISA） was used to measure serum free fatty acid （FFA） levels. ResultAt the end of the treatment， compared with the blank group， the model group exhibited significant increases in mouse body weight， FBG， FFA， TC， TG， and LDL-C levels （P<0.01）， along with significant hepatic lipid droplets， reduced hepatic glycogen， noticeable cholesterol accumulation in intestinal tissues， significantly decreased expression of FXR， SHP， PPARα proteins， and significantly increased expression of CYP7A1 protein in liver tissues （P<0.01）. Compared with the model group， the metformin group and the high- and medium-dose modified Gegen Qinliantang groups demonstrated significant reductions in mouse body weight， FBG， FFA， TC， TG， LDL-C levels （P<0.05， P<0.01）， significant increases in HDL-C levels （P<0.05， P<0.01）， decreased hepatic lipid accumulation， increased hepatic glycogen， reduced intestinal cholesterol accumulation， significantly increased expression of FXR， SHP， PPARα proteins， and significantly decreased expression of CYP7A1 protein in liver tissues （P<0.01）. ConclusionModified Gegen Qinliantang may regulate the FXR/SHP/PPARα signaling pathway to suppress FFA levels and improve lipid metabolism in T2DM mice.

Pyridine pigments from functional Monascus rice / 药学学报

The trace chemical components in functional Monascus rice were studied to explore the potential bioactive substances. MCI column, Sephadex LH-20 gel, and preparative liquid chromatography were used to purified the ethyl acetate extract from functional Monascus rice. Two novel pyridine Monascus pigments were isolated and identified, named monascopyridine G (1) and monascopyridine H (2), respectively based on extensive mass spectrometry (MS), infrared radiation (IR), and nuclear magnetic resonance (NMR) analysis. The molecular docking experiments between compounds 1 and 2 and peroxisome proliferators-activated receptor-gamma (PPARγ) showed that they exhibited obvious binding force with the receptor protein. Besides, the biosynthetic pathways of the two compounds were proposed, which provide a valuable reference for the selective production of these potential bioactive substances.

Gastrin attenuates sepsis-induced myocardial dysfunction by down-regulation of TLR4 expression in macrophages

Myocardial dysfunction is the most serious complication of sepsis. Sepsis-induced myocardial dysfunction (SMD) is often associated with gastrointestinal dysfunction, but its pathophysiological significance remains unclear. The present study found that patients with SMD had higher plasma gastrin concentrations than those without SMD. In mice, knockdown of the gastrin receptor, cholecystokinin B receptor (Cckbr), aggravated lipopolysaccharide (LPS)-induced cardiac dysfunction and increased inflammation in the heart, whereas the intravenous administration of gastrin ameliorated SMD and cardiac injury. Macrophage infiltration plays a significant role in SMD because depletion of macrophages by the intravenous injection of clodronate liposomes, 48 h prior to LPS administration, alleviated LPS-induced cardiac injury in Cckbr-deficient mice. The intravenous injection of bone marrow macrophages (BMMs) overexpressing Cckbr reduced LPS-induced myocardial dysfunction. Furthermore, gastrin treatment inhibited toll-like receptor 4 (TLR4) expression through the peroxisome proliferator-activated receptor α (PPAR-α) signaling pathway in BMMs. Thus, our findings provide insights into the mechanism of the protective role of gastrin/CCKBR in SMD, which could be used to develop new treatment modalities for SMD.

Effects of sodium arsenite on mitochondrial function and expression of SIRT1/PGC-1α pathway-related proteins in human normal liver cell / 环境与职业医学

Background Long-term exposure to arsenic can cause liver injury of varying degrees. Mitochondrial damage may be an early key event of arsenic-induced liver injury. Silent mating type information regulation 2 homolog 1 (SIRT1)/ recombinant peroxisome proliferators-activated receptor gamma coactivator 1 alpha (PGC-1α) is an important pathway regulating mitochondrial mass and function. However, whether arsenic-induced liver injury is related to mitochondrial dysfunction mediated by SIRT1/PGC-1α pathway remains unclear. Objective To investigate potential effects of sodium arsenite (NaAsO2) on mitochondrial function and expressions of SIRT1/PGC-1α pathway-related proteins in human normal liver cell. Methods Human normal liver cells (MIHA cells) were used as the research object. MIHA cells were treated with different concentrations of NaAsO2 (0, 5, 10 and 20 μmol·L−1) for 24 h, and the cells were collected for study. The ultrastructure of mitochondria was observed by transmission electron microscopy, adenosine triphosphate (ATP) concentration by fluorescence method, mitochondrial membrane potential (MMP) level by flow cytometry, and SIRT1, PGC-1α and their downstream nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM) protein expression levels by Western blotting. One-way analysis of variance and trend test were used for data statistical analysis. Results The viability of MIHA cells decreased gradually with the increase of NaAsO2 concentration (F=6495.47, P<0.001). The transmission electron microscope observation showed that the size of mitochondria in the 10 μmol·L−1 NaAsO2 treatment group was different, and the mitochondria were swollen or elongated in a rod-like shape. The mitochondria in the 20 μmol·L−1 NaAsO2 treatment group swelled like air spheres or vacuoles. The ATP concentration and MMP level of MIHA cells gradually decreased with the increase of NaAsO2 concentration (Ftrend of ATP=172.28, Ftrend of MMP=59.91, both Ps<0.001). Compared with the control group, the protein expression levels of SIRT1, PGC-1α, NRF1, and TFAM were not significantly changed in the 5 μmol·L−1 NaAsO2 treatment group, while the protein expression levels of SIRT1, PGC-1α, and TFAM were decreased in the 10 μmol·L−1 NaAsO2 treatment group, and the protein expression levels of SIRT1, PGC-1α, and NRF1 were decreased in the 20 μmol·L−1 NaAsO2 treatment group. The results of trend test showed that the protein expression levels of SIRT1, PGC-1α, NRF1, and TFAM decreased gradually with the increase of NaAsO2 concentration (Ftrend of SIRT1=47.07, P<0.001; Ftrend of PGC-1α=15.17, P<0.01; Ftrend of NRF1=13.54, P<0.01; F trend of TFAM=4.20, P<0.05). Conclusion The down-regulation of SIRT1/PGC-1α and its downstream NRF1 and TFAM may be involved in NaAsO2-induced mitochondrial dysfunction in liver cells.

Research and thinking of acupuncture on promoting white adipose tissue browning / 针刺研究

Acupuncture has become an effective approach in clinic for treating obesity, but its mechanism has not been clarified yet. A large number of researches have been conducted on the obesity mechanism in the aspects of neurophysiological regulation, feeding center regulation and peripheral digestion and absorption regulation at home and abroad. But, regarding the main storage site of excess energy, i．e. the remodeling and functional regulation of white adipose tissue (WAT), is still a new field in research. In the paper, focusing on the new filed of weight loss, in view of the promotion of WAT browning through the re-gulation of UCP1 and PPARγ signal pathway with acupuncture, the potential peripheral mechanism of acupuncture was explored on weight loss.

Effect of Electroacupuncture at Tinggong and Yifeng on D-galactose-induced Aging of Auditory Cortex through SIRT1/PGC-1α Pathway in Guinea Pigs / 听力学及言语疾病杂志

Objective To investigate the role of SIRT1/PGC-1α pathway in the auditory cortex aging of guinea pigs with age-related hearing loss and whether the electroacupuncture can delay aging process of the auditory cortex in the aged guinea pigs induced by D-galactose through the regulation of SIRT1/PGC-1α pathway.Methods Thirty 4-month-old guinea pigs were randomly divided into three groups including the control group (n=10),D-galactose group (model group,n =10),and D-galactose and electroacupuncture group (electroacupuncture group,n =10).The elderly group (n=10) was composed of 18-month-old guinea pigs.The guinea pigs in model group and electroacupuncture group had been subcutaneously injected with D-galactose(300 mg· kg-1· d-1)for 6 weeks.Moreover,the guinea pigs in electroacupuncture group electroacupunctured at Tinggong and Yifeng for 15 minutes half an hour later once a day.After 6 weeks,the ABR threshold of guinea pigs in each group was detected.The mRNA and protein expression of SIR1 and PG-C-1α in auditory cortex of guinea pigs were detected by real -time fluoreacence quantitative PCR and Western Blot.Results There was a significant increase in the ABR threshold of the model group and elderly group (P＜0.001,compared with the control group),decrease in the electroacupuncture group (P＜0.001,compared with the model group),and no significant difference between model group and elderly group(P＞0.05).There was significant decrease in the expression of SIRT1 and PGC-1α in the model groupand elderly group(P＜0.05,compared with the control group),and significant increase at mRNA and protein levels in the electroacupuncture group (P＜0.05,compared with the model group).Conclusion SIRT1/PG-C-1α pathway may play a role in aging process of the auditory cortex in the aged guinea pigs induced by D-galactose,and electroacupuncture at Tinggong and Yifeng may increase the antioxidant capacity of auditory cortex by activating SIRT1/PGC 1α in guinea pigs with age-related hearing loss,thus delaying the aging process of auditory cortex.

Curcumin inhibits advanced glycation end products-induced cell apoptosis and mitochondrial dysfunction via elevating PPARγ in chondrocyte / 中国药理学通报

Aim To explore the mechanism of the protective effect of curcumin on advanced glycation end products (AGEs)-induced chondrocyte apoptosis and mitochondrial dysfunction whether by elevating peroxisome proliferators-activated receptor-γ (PPARγ) or not.Methods The ratio of apoptotic cells was assayed by TUNEL;the mitochondrial membrane potential(△Ψm) was evaluated by Rhodamine-123 fluorescence.The ATP content was assayed by related kits.The activity of caspase-3 was detected by spectrophotometry.The expression of cytochrome C,Bax,and Bcl-2 was detected by Western blot.The PPARγ expression was determined by Western blot and real-time PCR;in addition,its activity was assayed by DNA-binding method.Results AGEs could induce chondrocyte apoptosis and up-regulate the levels of cytochrome C and caspase-3.Simultaneously,AGEs decreased the levels of △ Ψm and ATP production.Mitochondrial permeability conversion pore inhibitor cyclosporine A could significantly protect the cells from apoptosis.In addition,both PPARγ specific agonist pioglitazone and curcumin significantly inhibited AGEs-induced chondrocytes apoptosis and mitochondrial dysfunction.However,pretreatment with PPARγ specific inhibitor GW9662 (10 μ mol · L-1) could significantly antagonize the protective effect of curcumin on mitochondrial damage induced by AGEs.Curcumin could also significantly increase PPARγtranscriptional activity induced by AGEs,together with a significant induction of PPARγprotein and mRNA expression.Conclusion Curcumin could effectively protect AGEs-induced chondrocyte mitochondrial dysfunction by upregulating PPARγ,thus protecting chondrocytes from apoptosis.

Effects of telmisartan on the expressions of PPARs and adiponectin receptor2 in the liver tissue of rat with nonalcoholic steatohepatitis / 中国实验动物学报

Objective To explore the effects of telmisartan on expression of peroxisome proliferators PPARs activated receptors and adiponectin receptor 2 in rats with nonalcoholic steatohepatitis (NASH).Methods Forty male SD rats were randomized into normal-diet control group (NC,n=15),high fat-diet control group (FC,n=15),and high fat-diet with telmisartan group (FT,n =10).NC group was given standard diet and the other two groups were given high-fat diet.At the end of the 12th week,5 rats which were randomly selected from both the NC and FC groups were given euglycermic hyperinsulinemia clamp to see if fat-liver model of rats with insulin resistance was successfully induced,and rat livers were removed for pathological examination to determine the extents of NASH.Afterwards,rats in the FT group was given telmisartan (5 mg/kg·d) while rats in both the NC and FC groups were given the same volume of 0.9% saline solution by intragastric gavage for another 4 weeks.After glucose infusion rates (GIRs) were obtained by the euglycermic hyperinsulinemia clamp technique at the end of the 16th week,all rats were sacrificed and the body weight was recorded,and serum lipids,aminotransferases and fasting blood glucose were measured.The mRNA expressions of peroxisome proliferator activated receptors (PPARs),adiponectin receptor-2 and angiotensin II type-1 receptor in the liver tissue were assessed by semi-quantitative reverse transcriptase polymerase chain reactions.Results The expressions of PPARα,PPARγ and AdipoR2 mRNA in the liver tissue of FC group were decreased significantly compared with the NC group (P<0.01),and the expression of AT1R mRNA of the liver tissue in FC group was increased significantly compared with NC group (P<0.01).Compared with the FC group,the expressions of PPARα,PPARγ and AdipoR2 mRNA in the FT group were increased (P<0.01).Serum aminotransferases,lipids and fasting blood glucose level in the rats of FC group were increased significantly compared with rats of the NC group (P<0.01),and serum aminotransferases,lipids and fasting blood glucose level in the rats of FT group were greatly improved compared with the FC group.Conclusions Telmisartan can improve glucose and lipid metabolism,stop weight gain,decrease liver index,and alleviate steatosis and inflammation of NASH rats by improving insulin resistance.Telmisartan may play an effective role in the protection of rat liver with NASH.

Gegen Qinlian decoction activates PPARγ to ameliorate adipocytic insulin resistance in diabetic SD rats and IR-3T3-L1 adipocytes / 中国中药杂志

To investigate the effects of Gegen Qinlian decoction(GQD) in improving adipocytic insulin resistance(IR) and explore its related molecular mechanism. Diabetic rats models were induced by high glucose and high-fat diet with a small dose of streptozotocin, and after GQD treatment for 3 months, blood biochemical indexes such as fasting blood-glucose(FBG), insulin, glycosylated serum protein(GSP) and HOMA-IRI were detected and assessed. After the total RNA was extracted from the adipose tissue of diabetic SD rats, PPARγ, ADPN, GLUT4, GLUT2, ACACA and ACACB mRNA expression levels were separately detected by qPCR. Then, stable IR-3T3-L1 adipocyte model was built with 1 μmol•L⁻¹ dexamethasone. After the cell viability was detected by CCK-8 assay, 5%, 10% and 15% GQD-containing serum(GQD-CS) were respectively used to treat IR-3T-L1 adipocytes for 24 h. The contents of glucose, nonesterified fatty acid(NEFA) and adiponectin in cell culture supernatants were separately detected whereas the intracellular triglyceride(TG) contents of IR-3T3-L1 adipocytes were also measured. The ADPN, PPARγ and GLUT4 mRNA and protein expression levels were respectively detected by qPCR and Western blot in IR-3T3-L1 adipocytes. Results showed that GQD significantly decreased fasting blood glucose, insulin and GSP(P<0.01), and down-regulated HOMA-IRI(P<0.05) after the high-fat diet/streptozotocin-induced diabetic SD rats were treated for three months, with a good hypoglycemic effect. Moreover, PPARγ, ADPN, GLUT4, GLUT2, ACACA and ACACB mRNA expression levels were significantly elevated in the adipose tissue of GQD-treated diabetic SD rats. The 5%, 10% and 15% GQD-CS significantly increased glucose consumption of IR-3T3-L1 adipocytes at 24 h treatment(P<0.01), significantly decreased the intracellular TG content (P<0.01), and down-regulated NEFA to a certain extent but not significantly. Moreover, GQD-CS significantly up-regulated GLUT4 and ADPN expression. The results indicated that GQD could activate PPARγ to ameliorate adipocytic insulin resistance in the diabetic SD rats and IR-3T3-L1 adipocytes.

Rhinacanthus nasutus leaf improves metabolic abnormalities in high-fat diet-induced obese mice

Objective: To investigate the effect of Rhinacanthus nasutus (R. nasutus) leaf extract on impaired glucose and lipid metabolism in obese ICR mice. Methods: Obesity was induced in the male ICR mice by feeding them a high-fat diet (60 kcal% fat) for 12 weeks. After the first six weeks of the diet, the obese mice were administered with the water extract of R. nasutus leaves at 250 and 500 mg/kg per day for the next six weeks. Subsequently, the blood glucose, lipid profiles, insulin, leptin, and adiponectin levels were measured. The liver and adipose tissues were excised for histopathological examination and protein expression study. Results: After six weeks of the treatment, R. nasutus extract (at 250 and 500 mg/kg per day) was found to reduce the elevated blood glucose level, improve the insulin sensitivity, decrease the serum leptin, and increase the serum adiponectin levels. The obese mice treated with R. nasutus were found to have a reduction in the increased lipid concentrations in their serum and liver tissues. Moreover, treatment with R. nasutus reduced the fat accumulation in the liver and the large adipocyte size in the fat tissues. Interestingly, the administration with R. nasutus extract was marked by an increase in the hepatic peroxisome proliferators-activated receptor alpha, fat cell adiponectin, and glucose transporter 4 proteins. Conclusions: To the best of our knowledge, the present study is the first report on the impact of R. nasutus extract in improving the impaired glucose and lipid metabolism in high-fat diet-induced obesity in mice via stimulating the insulin sensitivity in the liver and adipose tissues.

Interference of DEHP on the key genes of glucose and lipid metabolism in HepG2 cells / 中国职业医学

OBJECTIVE: To investigate the effects of di-( 2-ethylhexyl) phthalate( DEHP) on the expression of the key genes involved in glucose and lipid metabolism,and explore the toxicity of DEHP on the glucose and lipid metabolism in HepG2 cells cultured in vitro. METHODS: HepG2 cells in logarithmic growth phase were divided into DEHP exposure group and control group. The exposure group was exposed to DEHP with different final concentrations( 5,10,50,100,500 and1 000 μmol / L),and the control group was exposed to dimethyl sulfoxide of corresponding concentrations. After 24 hours of DEHP exposure,real-time fluorescence quantitative polymerase chain reaction( Q-PCR) was applied to detect the level of mRNA transcription of peroxisome proliferators-activated receptor α( PPARα), which is an endogenous marker indicating the success of DEHP exposure. In addition,the level of mRNA transcription of key genes involved in glucose and lipid metabolism were also measured by Q-PCR,including glucose-6-phosphatase( G-6-Pase),phosphoenolpyruvate carboxykinase( PEPCK),stearoyl-coenzyme A desaturase 1( SCD1),fatty acid synthase,sterol regulatory elementbinding protein 1c and acetyl Co A carboxylase 1. P ≤0. 008 was considered as statistical significance. RESULTS: After DEHP exposure,the mRNA transcription level of PPARα was significantly elevated in all exposure groups( P < 0. 008)except for 5 μmol / L DEHP exposure group,which indicated the successful establishment of DEHP exposure model. The mRNA transcription level of G-6-Pase was significantly increased in 100 and 500 μmol / L DEHP exposure groups( P ≤0. 008) when compared with the controls; the PEPCK mRNA transcription level of showed no significant differences between the 6 DEHP exposure groups and their corresponding control groups( P > 0. 008). The mRNA transcription level of SCD1 was significantly down-regulated in 100 μmol / L DEHP exposure group( P < 0. 008) when compared with its control. The mRNA transcription level of other key genes involved in the lipid metabolism were not significantly altered after DEHP exposure( P > 0. 008). CONCLUSION: The effect of DEHP on glucose metabolism was mainly manifested by promoting G-6-Pase gene expression,which is the rate-limiting enzyme for gluconeogenesis. The effect of DEHP on the lipid metabolism of HepG2 cells was limited.

Regulation of Nrf2 pathway to protect ventilator induce lung injury in vivo via inhibition of caveolin ;phosphorylation / 中华危重病急救医学

Objective To investigate whether the inhibition of caveolin-1 (Cav-1) phosphorylation will regulate effectively nuclear factor-erythroid 2-related factor (Nrf2) signal pathway and downstream effector molecules and protest against ventilation induced lung injury (VILI) in an animal model in vivo. Methods Ninety male Sprague-Dawley (SD) rats were randomly divided into nine groups (each n = 10): sham group in which rats did not receive ventilation but received tracheotomy; lung protective ventilation (PV) for 1 hour or 2 hours group; mechanical ventilation (MV) at high volume tidal (VT, 40 mL/kg) for 1 hour or 2 hours group; protein tyrosine kinase inhibitor PP2 or rosiglitazone (Rsg) pretreatment + high VT ventilation for 1 hour or 2 hours groups. The two pretreatment groups were given intraperitoneal injection PP2 15 mg/kg or intragastric administration of Rsg 5 mg/kg 1 hour before ventilation respectively. The rats were sacrificed after model reproduction, and bronchoalveolar lavage fluid (BALF) was collected. Pulmonary vascular permeability was measured by Evans blue (EB). The levels of tumor necrosis factor-α (TNF-α), activator protein-1 (AP-1), nuclear factor-κB (NF-κB), and interleukin-8 (IL-8) in BALF were determined by enzyme linked immunosorbent assay (ELISA). Then the lung tissues were collected, the lung wet/dry ratio (W/D) was calculated, the changes in pathology was observed with light microscope, and myeloperoxidase (MPO) activity was determined by colorimetric analysis. Nrf2 mRNA was determined by reverse transcription-polymerase chain reaction (RT-PCR). The expressions of Cav-1 tyrosine residues 14 phosphorylation (pCav-1-Y14), Cav-1, peroxisome proliferators-activated receptor γ (PPARγ) and claudin-5 as well as Nrf2 in cytoplasm and nucleus were determined by Western Blot. The positive expressions of PPARγ and claudin-5 in lung tissues were assayed with immunohistochemistry staining. Results There were no obvious pathological changes in the lung tissue in sham group and PV groups, and there were no significant differences in all the parameters between the two groups either. However, the injury in lung tissue was severe in the high VT groups in which W/D ratio, EB contents, MPO activity, and TNF-α, AP-1, IL-8, NF-κB levels in BALF as well as the protein expressions of Cav-1 and pCav-1-Y14 were significantly higher than those of sham group and PV groups, and the protein expressions of PPARγ and claudin-5 were significant lower than those of sham group and PV groups with a dose-dependent manner; but Nrf2 expressions in cytoplasm and nucleus did not show a statistical increase. After pretreatment of PP2 or Rsg, W/D ratio, MPO activity, EB contents, TNF-α, AP-1, IL-8, and NF-κB in BALF were significantly decreased as compared with those of high VT group, and RT-PCR showed significant up-regulation of Nrf2 mRNA in lung tissues too. Moreover, there was a statistically significant increase in expressed Nrf2 proteins in nucleus in PP2 or Rsg groups as compared with those of high VT groups [Nrf2 in nucleus (gray value): 0.61±0.06, 0.56±0.06 vs. 0.31±0.02 at 1 hour, 0.38±0.06, 0.43±0.07 vs. 0.22±0.03 at 2 hours; all P < 0.05], but no significant difference was found in the expression of Nrf2 protein in the cytoplasm among all groups. The protein expressions of pCav-1-Y14 in PP2 pretreatment groups were significantly lower than those of high VT groups (gray value: 0.89±0.04 vs. 1.48±0.02 at 1 hour, 0.86±0.02 vs. 1.31±0.01 at 2 hours; both P < 0.05); but expressed PPARγ proteins and expressed claudin-5 proteins in PP2 or Rsg pretreatment groups were significantly higher than those of high VT groups [PPARγ (gray value): 0.34±0.07, 0.42±0.13 vs. 0.17±0.07 at 1 hour, 0.38±0.09, 0.33±0.07 vs. 0.16±0.03 at 2 hours; claudin-5 (gray value): 0.33±0.05, 0.38±0.07 vs. 0.14±0.03 at 1 hour; 0.30±0.06, 0.31±0.04 vs. 0.17±0.04 at 2 hours; all P < 0.05]. Conclusions The inhibition of Cav-1-Y14 phosphorylation can increase the expression of Nrf2 in the nucleus, then result in an increase in the protein expressions of PPARγ and claudin-5 of its effector molecules. This effect can reduce the inflammation and capillary permeability of lung tissue in the model of VILI.

Effect of peroxisome proliferator-activated receptor γagonist rosiglita-zone on intestinal injury in rats undergoing orthotopic autologous liver transplantation by inhibiting inflammatory response / 中国病理生理杂志

AIM: To investigate the effect of rosiglitazone , a peroxisome proliferators-activated receptor γ(PPARγ) agonist, on the expression of PPARγ, the activation of NF-κB and intestine injury in the rats undergoing ortho-topic autologous liver transplantation ( OALT ) .METHODS: Sprague-Dawley male rats were randomly divided into 4 groups:control group, sham group, OALT group and rosiglitazone (0.3 mg/kg, iv) pretreatment (ROS+OALT) group. The OALT model was established , and the intestinal tissues were collected 8 h after the liver reperfusion .The intestinal tis-sue sections were stained to visualize the damage .The expression of PPARγand NF-κB in the tissues, the concentrations of diamine oxidase (DAO) and fatty acid-binding protein 2 (FABP2) in the serum and the concentration of TNF-αand IL-6 in the tissues were measured .RESULTS:Compared with sham group , the intestinal mucosa of the rats showed obvious pathological injury after liver reperfusion in OALT group and ROS group , the Chiu’s scores of intestinal mucosa was signifi-cantly higher , and the serum concentrations of DAO and FABP 2 increased ( P<0.05 ) .After rosiglitazone pretreatment , the injury of intestinal mucosa of the rats was alleviated , the Chiu’s scores was lower and the serum concentrations of DAO and FABP2 decreased (P<0.05), the PPARγexpression was obviously up-regulated in the intestinal tissues, the nuclear translocation of NF-κB was reduced and the concentrations of IL-6 and TNF-αwere decreased .CONCLUSION: During perioperative period of OALT in rats , the inflammatory responses are obvious .Furthermore, obvious intestinal injury oc-curs .PPARγagonist rosiglitazone obviously up-regulates PPARγexpression and inhibits the inflammation in the intestines , thus protecting against intestinal injury in rats undergoing OALT .

Research progress on natural products on new targets of type 2 diabetes / 中草药

Type 2 diabete, caused by inadequate secretion of insulin and insulin resistance in tissues and organs, is also called non insulin dependent diabete. At present, over 90% diabetes is type 2 diabete which is seriously harmful to human health, however, the current clinical application of chemical synthetic medicines have different degrees of side effects. Therefore, the study of components with antidiabetic activity acting on different targets from the natural products with low toxicity has become a focus of current research. The new targets, such as PTP1B, DPP-IV, PPAR, and AMPK, were discovered in recent years. In this paper, active components in natural products on new targets for diabetes are reviewed, so as to provide the reference for the further research of diabetes.

Effects of exercises on the lipid metabolism and expression of PPAR-α mRNA in skeletal muscles of ApoE knockout mice / 中华物理医学与康复杂志

Objective To observe the influence of exercises on the mRNA expression of peroxisome proliferator-activated receptor (PPAR-α) and its target genes of acyl-CoA oxidase (ACO),Enoyl-CoA-hydratase and 3-hydroxyacyl-CoA-dehydrogenase (EHHADH) in the skeletal muscles in insulin-resistance mice to develop a way to improve the lipid metabolism.Methods Twenty male ApoE knockout mice were randomly divided into two groups,the high-fat diet group (group HFD) and the exercise training group (group Ex).The HFD group were fed with highfat diet,while the Ex group were fed in the same way,with additionally swimming training.And ten healthy male C57BL/6j mice were chosen as the control group(group ND).After 12 weeks of intervention,the serum lipid,blood glucose and insulin levels were determined,and homeostasis model assessment insulin resistance index (Homa-IRI) was calculated.The bilateral gastrocnemiuses were cut to be observed under a transmission electron microscope,and the mRNA expression of PPAR-α,ACO and EHHADH in skeletal muscle were measured using reverse transcription polymerase chain reaction(RT-PCR).Results The transmission electron microscope showed that the sarcolemma edema,mitochondrial swelling,as well as focal myocytolysis and edema within myofibrils were observed in the HFD group.The total cholesterol,low-density lipoprotein cholesterol,free fatty acid,fasting glucose,insulin and HomaIRI of the HFD group were significantly higher than the control group (P ＜ 0.05),while the mRNA expression of PPAR-α,ACO and EHHADH was significantly deceased than the latter(P ＜ 0.05).After swimming,the abovementioned pathological changes disappeared.The serum lipid of the Ex group were significantly lower (P ＜ 0.05),while HDL was significantly higher (P ＜ 0.05).And fasting insulin,glucose and HOMA-IR of the Ex group were significantly lower (P ＜ 0.05),while the mRNA expression of the above in the Ex group were significantly increased (P ＜0.05).Conclusion Swimming training could improve insulin resistance and metabolic disorder of lipid of ApoE knockout mice.The possible mechanisms may be through up-regulating the expression of PPAR-α,which in turn stimulates the expression of ACO and EHHADH mRNA to strengthen fatty acid β-oxidation.

The protective effect of rosiglitazone on renal injury of severe acute pancreatitis / 中华急诊医学杂志

ObjectiveTo investigate the effects of rosiglitazone, the agent of highly selective peroxisome proliferator-activated receptor-γ agonist, on the renal injury of rats with severe acute pancreatitis. MethodsFifty-four male Wistar rats were randomly (random number) divided into three groups : sham operation group ( SO group), severe acute pancreatitis group ( SAP group ) and rosiglitazone pretreatment group (ROSI group) . Severe acute pancreatitis model was induced by retrograde infusion of 5％ sodium taurocholate into the biliopancreatic duct. Rosiglitazone (6 mg/kg) dissolved in 10％ DMSO were injected into the femoral vein 30 minutes prior to the modeling. The solution of 10％ DMSO was given to rats of SO group and SAP group. Rats were sacrificed 3, 12 and 24 h after modeling. The levels of serum amylase, serum creatinine, urea nitrogen, urinary albumin, urinary lgG and αl-microglobulin were measured and analyzed statistically. Kidney tissue samples were stained respectively with hematoxylin and eosin for histopathological evaluation.Results The levels of serum amylase, serum creatinine, urea nitrogen, urinary albumin, urinary IgG and αl-microglobulin were significantly increased (P ＜ 0. 05 )after modeling, while lesser increases were found in ROSI group 12 h and 24 h after modeling (P ＜0. 05)compared with those in SAP group. ConclusionsRenal injury can be induced by severe acute pancreatitis,while Rosiglitazone protects rats from renal injury in the setting of severe acute panereatitis.

Polimorfismo Pro12Ala del gen PPAR-γ 2 y síndrome metabólico: Estudio preliminar / Pro12Ala polymorphism of the PPAR-gamma2 gene and the metabolic syndrome: Preliminary study

El objetivo de este estudio fue determinar la prevalencia del polimorfismo Pro12Ala del gen PPARgamma2 en individuos no emparentados con síndrome metabólico de la ciudad de Maracaibo. Se seleccionaron 50 individuos (22 con síndrome metabólico y 28 sin síndrome metabólico) entre 22 y 58 años. A cada individuo se le realizó una evaluación clínica, nutricional y bioquímica. Para analizar la secuencia de la variante Pro12Ala del gen PPAR se empleó PCR y digestión enzimática de los fragmentos de restricción del polimorfismo (PCR-RFLP). En los individuos con síndrome metabólico el porcentaje de portadores del alelo Ala fue de 13,6%, mientras que en el grupo sin síndrome metabólico fue de 32,14%. La frecuencia para el alelo Ala del polimorfismo Pro12Ala fue de 0,12 y para el alelo Pro fue de 0,88. Los individuos con síndrome metabólico y portadores del alelo Ala presentaron niveles más bajos de triglicéridos y col-HDL más alto. Se concluye que la presencia del alelo Ala en individuos con síndrome metabólico mostró un efecto protector sobre el perfil lipídico.

The aim of this paper was to determine the prevalence of the polymorphism pro12ala in non-related individuals with metabolic syndrome from Maracaibo-Venezuela. Fifty subjects (22 with metabolic syndrome and 28 without metabolic syndrome) between 22 to 58 years of age were selected. For each individual, biochemical, nutritious, and clinical evaluations were carried out. PCR and restriction-fragment length polymorphism enzyme digestion were used to analyze the Pro12Ala sequence variant of the PPAR gene. The distribution of the Ala allele was 13.6% in the individuals with metabolic syndro- and 32.14% in the group without metabolic syndrome. The frequency distributions of the PPAR gamma sequence variants were 0.12 for Ala variant and 0.88 for Pro. The subjects with the metabolic syndrome and carriers of the Ala 12 allele had lower concentration of triglycerides and higher HDL-C. It can be concluded that the Ala12 allele in individuals with metabolic syndrome had a protective effect on the lipid profile.

The protective effect of sodium hyaluronate on the cartilage of rabbit osteoarthritis and its effects on PPAR-gamma mRNA expression / 中华风湿病学杂志

Objective To observe the protective effect of sodium hyaluronate (Na-HA),and its effects on mRNA expression of peroxisome proliferators-activated receptor gamma (PPAR-γ) in cartilage of rabbit osteoarthritis (OA) model.Methods Forty eight white rabbits were divided into A,B,C groups randomly.Group A were normal controls,groups B and C were underwent unilateral anterior cruciate ligament transection (ACLT).The rabbits in group B were injected normal saline after ACLT;Group C rabbits received intra-articular 1% sodium hyaluronate (HA) injections 5 weeks after surgery,0.3 ml once a week.At week 11 after the surgery,all rabbits were sacrificed.The cartilage changes on the medial femoral condyles were graded.Cartilage sections were stained with safranin-O and HE,mRNA expression of PPAR-γ was detected by real time polymerase chain reaction (Real Time-PCR).Results Cartilage degeneration in group B was significantly more severe than in groups A and C.The grey value of Safranin-O of B group were higher than groups A and C.Expression of PPAR-γ mRNA in group B was higher than that in groups A and C.Conclusion NaHA has a protective effect on articular cartilage degeneration,and the inhibitory effect on PPAR-γ mRNA expression may be one of the therapeutic mechanism of Na-HA.

The Protective Effect of Sodium Hyaluronate on the Cartilage of Rabbit Osteoarthritis by Inhibiting Peroxisome Proliferator-Activated Receptor-Gamma Messenger RNA Expression

PURPOSE: The purpose of this study was to study the protective effect and influence of sodium hyaluronate (Na-HA) on mRNA expression of peroxisome proliferators-activated receptor gamma (PPAR-gamma) in cartilage of rabbit osteoarthritis (OA) model. MATERIALS AND METHODS: Forty eight white rabbits were randomly divided into A, B, and C groups. Group A was normal control group, B and C groups underwent unilateral anterior cruciate ligament transection (ACLT). The rabbits in group B were injected normal saline after ACLT; and Group C received intraarticular1% sodium hyaluronate (HA) injection 5 weeks after surgery, 0.3 mL once a week. At 11th week after surgery, all the rabbits were sacrificed. The cartilage changes on the medial femoral condyles were graded separately. Cartilage sections were stained with safranin-O and HE, and messenger RNA (mRNA) expression of PPAR-gamma was detected by using real time polymerase chain reaction (Real Time-PCR). RESULTS: Cartilage degeneration in group B was significantly more severe than in A and C injection group. The grey value of Safranin-O of B group was higher than A and C groups. Expression of PPAR-gamma mRNA in group B was higher than group A and C. CONCLUSION: This study shows that Na-HA has a protective effect on articular cartilage degeneration, and the inhibitory effect on the PPAR-gamma mRNA expression may be one of therapeutic mechanism of Na-HA.

Effects of peroxisome proliferators activated receptor-ganmma(PPAR-γ)on ischemia-reperfusion injury of bilr ducts after orthotopic liver transplantationwith / 中华急诊医学杂志

Objective To explore the effects and mechanism of peroxisome proliferators activated receptor-gamma(PPAR-γ)and its ligand rosiglitazone on ischemia-reperfusion injury of the donor bile ducts.Method Forty-two SD rats were randomly divided into three groups with fourteen rats in each:the sham operation group (SO),ischemia-reperfusion(I/R)group and I/R+rosiglitazone group(I/R+Ros).The animal model of is-chemia-reperfusion occurred in the orthotopically transplanted liver was used.Tne signal pathway of iuflanunatory response of bile duets of the transplanted hver and the variations of associated cytokines were detected by the signal transduction pathway-finder gene array and cytokine antibody chips.The pathological changes and the biochemical markers of the donor liver were assessed by histopathological score and the estimation of the functional changes of some other organs.Data were analyzed by using SPSS version 10.0 software package.Statistical analysis was car-ried out by using one-way anova and Bonferroni test.Results Compared with the SO group and I/R+Ros group.the expression of NF-кB gene of I/R group to more than two times,and the levels of IL-1α,IL-1β and TNF-α pro-tein expressions in I/R group went up over double too.Compared with I/R group,the histopathological score and the biochemical markers of I/R+Ros group were significantly lower (P＜0.05,P＜0.01,respectively).Con-clusions PPAR-γ and its ligand rosiglitazone have protective effects on ischemia-reperfusion injury to donor bile ducts.The mechanism may be attributed to decrease in the release of inflammatory mediators(IL-1α,IL-1β,TNF-α and so on)resulted from the down-expression of decreased due to NF-кB.