白虎加人参汤对2型糖尿病大鼠抗氧化应激作用及机制研究

Effect and mechanism of Baihu jia Renshen decoction on anti-oxidative stress in type 2 diabetic rats

目的:研究白虎加人参汤(BHJRS)对2型糖尿病(T2DM)模型大鼠抗氧化应激的作用,并初步探讨其作用机制。方法:随机取8只SD大鼠作为对照组(NC组),其余SD大鼠采用高脂高糖联合低剂量腹腔注射STZ(45 mg/kg)制备T2DM大鼠模型。将成模大鼠随机分为模型(DM)组、阳性药[盐酸二甲双胍(Met),200 mg/kg]组、BHJRS高剂量组(BHJRS-H,BHJRS溶液37.8 g/kg)、BHJRS低剂量组(BHJRS-L,BHJRS溶液18.9 g/kg),连续给药8周。测定各组大鼠第0、2、4、6、8周空腹血糖(FBG),检测糖化血红蛋白(HbAlc)、胰岛素(INS)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)水平并计算ISI值,观察胰腺组织病理学形态变化;检测胰腺组织中B淋巴细胞瘤-2基因(Bcl-2)、胱天蛋白酶3(Caspase-3)、Bcl-2相关X蛋白(Bax)的mRNA和蛋白水平;检测胰腺组织中蛋白激酶B(AKT)/糖原合成激酶-3β(GSK-3β)/核因子NF-E2相关因子(Nrf2)信号通路关键蛋白的表达。结果:与DM组比较,Met组、BHJRS-H组和BHJRS-L组显著降低T2DM大鼠FBG、血清中HbAlc、MDA水平(P<0.05),显著升高血清中INS、CAT、SOD、GSH-Px水平和ISI值(P<0.05);显著上调胰腺组织中p-AKT/AKT、p-GSK-3β/GSK-3β、n-Nrf2、血红素加氧酶-1(HO-1)水平(P<0.05),显著下调Bax/Bcl-2、Caspase-3、n-Fyn水平(P<0.05),胰腺组织病理变化均不同程度改善。结论:BHJRS对胰腺组织有一定的抗氧化应激作用,其原因可能在于调节AKT/GSK-3β/Nrf2信号通路中相关蛋白的表达有关。

Objective:To study the effect and mechanism of Baihu jia Renshen decoction(BHJRS)on oxidative stress in Type 2 diabetic rats,and to explore its mechanism.Methods:Eight SD rats were randomly selected as the control group(NC group),and the remaining SD rats were treated with high fat and high sugar combined with low dose of STZ(45 mg/kg)intraperitoneally to create T2DM rat model.The model rats were randomly divided into a model(DM)group,a positive drug[metformin(Met),200 mg/kg group],a BHJRS high-dose group(BHJRS-H,37.8 g/kg),a BHJRS low-dose group(BHJRS-L,18.9 g/kg).The drug was administered continuously for 8 weeks.FBG was measured at the 0,2,4,6 and 8 weeks in each group,and the levels of HbAlc,INS,MDA,GSH-Px,SOD and CAT were detected,and ISI values were calculated.The morphological changes of pancreatic histopathology were observed.The mRNA and protein levels of Bcl-2,Bax and Caspase-3 were detected in pancreatic tissue.The expression of AKT/GSK-3β/Nrf2 signaling pathway in pancreatic tissue was detected.Results:Compared with DM group,the levels of FBG,serum HbAlc and MDA in Met group,BHJRS-H group and BHJRS-L group were significantly decreased(P<0.05),and the levels of INS,CAT,SOD,GSH-Px and ISI in serum were significantly increased(P<0.05).Significantly increased the p-Akt/AKT ratio,p-GSK-3β/GSK-3βratio,n-Nrf2 and heme oxygenase-1(HO-1)levels in pancreatic tissue(P<0.05),and significantly decreased the Bax/Bcl-2 ratio,Caspase-3 and n-Fyn levels(P<0.05).The histopathologic changes of pancreas were improved in different degree.Conclusion:BHJRS has a certain effect on the anti-oxidative stress of pancreatic tissue,and its mechanism may be related to the regulation of the expression of related proteins in the AKT/GSK-3β/Nrf2 signaling pathway.