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Effects of oxymatrine on reproductive injury and Nrf2/HO-1 signaling pathway in type 2 diabetic male rats
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DOI   10.11656/j.issn.1672-1519.2023.09.15
Key Words   oxymatrine;type 2 diabetes mellitus;reproduction;testicle;oxidative stress;Nrf2/HO-1 signaling pathway
Author NameAffiliation
YANG Fang Handan Central Hospital, Handan 056008, China 
MA Jingfen Handan Central Hospital, Handan 056008, China 
ZHENG Congcong Handan Central Hospital, Handan 056008, China 
WEI Zhikun Handan First Hospital, Handan 056002, China 
Abstract
    [Objective] To investigate the effects of oxymatrine(OMT) on reproductive injury and E2 related factor 2(Nrf2)/heme oxygenase-1(HO-1) signaling pathway in type 2 diabetic(T2DM) male rats. [Methods] The T2DM rat model was prepared by high-fat diet combined with intraperitoneal injection of streptozotocin. And the normal group,model group,metformin(Met) group and OMT low-dose,medium-dose,high-dose groups were set up,with 8 rats in each group. The Met group was given 200 mg/kg by intragastric administration once a day;the OMT low,medium,high dose groups were given 25,50 and 100 mg/kg by intragastric administration once a day;and the normal group and model group were given normal saline intragastric administration once a day;and the course of treatment was 4 weeks. The levels of fasting blood glucose(FBG) and serum testosterone(T),gonadotropin-releasing hormone(GnRH),luteinizing hormone(LH),follicle-stimulating hormone(FSH) in serum were detected;the testicular mass and volume were measured;the histopathological changes of testicle were observed by HE staining,the seminiferous tubules diameter(STD) and thickness of the seminiferous epithelium(TSE) were measured. The sperm count,sperm survival rate and sperm motility were detected through semen analyzer. The activity of antioxidant enzymes(SOD and GSH-Px) and the content of MDA in testicular tissue were detected by colorimetry. The expressions of Nrf2,HO-1 mRNA were detected by RT-PCR;the expressions of Nrf2,p-Nrf2,HO-1 protein were detected by Western blot. [Results] Compared with the model group,the level of FBG in Met group and OMT low,medium,high dose groups were decreased,and the level of T,GnRH,LH,FSH in serum were increased(P<0.05);the testicular mass and volume were increased(P<0.05). The testicular histopathological changes were significantly improved,and the STD,TSE were increased(P<0.05). The sperm count,sperm survival rate,sperm motile of(a+b) grade were increased(P<0.05). The activity of SOD,GSH-Px were increased,while the content of MDA was decreased(P<0.05). The expression of Nrf2,HO-1 mRNA were increased,and the expressions of Nrf2,p-Nrf2,HO-1 protein were increased(P<0.05). The effects of OMT low,medium,high dose groups were dose-dependent(P<0.05). Except for FBG and GSH-Px,the effect of OMT high dose group on other indexes were better than those of Met group(P<0.05). [Conclusion] OMT has protective effect on reproductive injury in T2DM male rats,and its mechanism may be related to the activation of Nrf2/HO-1 signaling pathway,inhibition of oxidative stress,and improvement of hypothalamic-pituitary-gonadal axis function.

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