袖状胃减容术对2型糖尿病大鼠肝脏Nrf2介导的氧化应激反应的影响

Effect of sleeve-shaped gastric volume reduction surgery on Nrf2-mediated oxidative stress in liver of type 2 diabetic rats

目的观察袖状胃减容术对2型糖尿病大鼠肝脏的保护作用,初步探讨其作用机制。方法SPF级SD大鼠45只,采用腹腔注射STZ法诱导2型糖尿病大鼠模型,模型成功后随机分为2型糖尿病大鼠模型组(DM组)、袖状胃减容术干预组(SG组),假手术组(Sham组),术后连续观察8周,ELISA法检测各组大鼠肝损伤标志物ALT、AST及氧化应激细胞因子MDA、SOD、GSH表达水平,HE染色观察病理学变化,Western blot及qPCR法检测Nrf2、HO-1表达水平。结果STZ诱导后的糖尿病大鼠,于8w后出现明显的肝功能损伤及氧化应激反应,血清ALT、AST、MDA含量明显升高,SOD、GSH含量明显降低,病理学可见肝脏组织结构模糊,肝小叶内出现局灶性坏死,部分肝细胞颗粒样变性。袖状胃减容术术后8w,SG组大鼠肝功能明显得到改善,血清ALT、AST、MDA含量明显降低,SOD、GSHSD明显升高,同时上调Nrf2、HO-1的表达水平。结论袖状胃减容术改善糖尿病大鼠机体内高糖环境下肝功能损伤,与其上调Nrf2、HO-1的表达,抑制肝脏氧化应激反应相关。

Objective To observe the protective effect of sleeve-shaped gastric volume reduction surgery on liver of type 2 diabetic rats and explore its mechanism of action.Methods A total of 45 SPF SD rats were induced by intraperitoneal injection of STZ,and randomly divided into:2 type diabetic rat model group(DM group)and sleeve gastric dilatation intervention group(SG),and Sham operation group.8 weeks later,the expressions of ALT,AST and oxidative stress cytokines MDA,SOD and GSH in liver injury were detected by ELISA.Pathological changes were observed by HE staining,and the expressions of Nrf2 and HO-1 were detected by Western blot and qPCR.Results The liver function damage and oxidative stress were observed,the contents of ALT,AST and MDA in serum were significantly increased,but decreased for SOD and GSH,with blurred structure of liver and focal necrosis of hepatic lobules and some degenerated hepatocytes 8 weeks after STZ-induction.However,the liver function was significantly improved,the contents of ALT,AST,MDA in serum were significantly decreased,but increased for SOD and GSH,and up-regulated for Nrf2 and HO-1 in SG group.Conclusion Sleeve-shaped gastric volume reduction improved liver function damage,which was related to up-regulating the expression of Nrf2 and HO-1 and inhibiting oxidative stress.in diabetic rats.