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Exploring the therapeutic effects and action mechanism of polydatin on gestational diabetes mellitus rats based on Nrf2/HO-1 pathway
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DOI   10.11656/j.issn.1673-9043.2024.07.07
Key Words   polydatin;Nrf2/HO-1;gestational diabetes mellitus;action mechanism
Author NameAffiliationE-mail
ZHOU Fangfang Department of Obstetrics 1, Xinxiang Central Hospital, Xinxiang 453099, China  
LIU Yu Department of Obstetrics 1, Xinxiang Central Hospital, Xinxiang 453099, China  
MA Shuangling Department of Obstetrics 1, Xinxiang Central Hospital, Xinxiang 453099, China  
LI Xiaoqian Department of Obstetrics 1, Xinxiang Central Hospital, Xinxiang 453099, China  
ZHANG Xinning Department of Obstetrics 1, Xinxiang Central Hospital, Xinxiang 453099, China  
LI Cimei Department of Obstetrics 1, Xinxiang Central Hospital, Xinxiang 453099, China  
BI Jingjing Department of Obstetrics 1, Xinxiang Central Hospital, Xinxiang 453099, China  
LI Guoyun Department of Obstetrics 1, Xinxiang Central Hospital, Xinxiang 453099, China 2284499658@qq.com 
Abstract
    [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.

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