Exploring the therapeutic effects and action mechanism of polydatin on gestational diabetes mellitus rats based on Nrf2/HO-1 pathway
[Objective]To explore the therapeutic effect and action mechanism of polydatin(PD)on gestational diabetes mellitus(GDM)rats.[Methods]Female SD rats were fed with high fat and high sugar for 8 weeks,and 84 pregnant rats were prepared in the same cage.They were randomly grouped into 7 groups(12 rats/group):control group,Model group,PD low,medium,and high dosage groups(30,75,150 mg/kg),positive control group(200 mg/kg metformin hydrochloride),and inhibitor group[150 mg/kg PD+30 mg/kg nuclear factor erythroid-2 related factor 2(Nrf2)/heme oxygenase 1(HO-1)pathway inhibitor ML385].Except for the control group,the other groups were intraperitoneally injected with streptozotocin(35 mg/kg)to replicate the GDM rat model after 5 days of pregnancy.The body mass and fasting blood glucose(FBG)of pregnant rats in each group were measured;the levels of fasting insulin(FINS),interleukin(IL)-6,IL-1β and tumor necrosis factor(TNF)-α were measured by ELISA,the homeostasis model assessment-IR(HOMA-IR),islet β cell function index(HOMA-β)and insulin sensitive index(ISI)were calculated;the levels of serum lipids in rats were analyzed by automatic biochemical analyzer;HE staining was used to observe the damage of pancreatic tissue in rats;Western Blot was applied to detect the expression of Nrf2 and HO-1 signal pathway proteins in the pancreas of rats in each group.[Results]Compared with the control group,the body mass,the levels of FBG,FINS,HOMA-IR,IL-6,IL-1β,TNF-α,the contents of total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),free fat acid(FFA)in the model group were obviously increased,the contents of ISI,HOMA-β,high-density lipoprotein cholesterol(HDL-C),the number of islets,the expression of Nrf2 and HO-1 proteins were obviously decreased(P<0.05);compared with the model group,the body mass,the levels of FBG,FINS,HOMA-IR,IL-6,IL-1β,TNF-α,the contents of TC,TG,LDL-C,FFA in the low,middle and high dose PD groups were obviously decreased,the contents of ISI,HOMA-β,HDL-C,the number of islets,the expression of Nrf2 and HO-1 proteins were obviously increased(P<0.05);compared with the positive control group,there was no obvious difference in the above indexes in the high-dose PD group(P>0.05);Nrf2/HO-1 pathway inhibitor ML385 could reverse the protective effect of high-dose PD on GDM rats(P<0.05).[Conclusion]PD improves GDM by reducing blood glucose,blood lipid and inflammatory response.The mechanism may be related to the activation of Nrf2/HO-1 signaling pathway.
万方数据
维普
