基于线粒体融合-分裂系统探讨参芪化痰方改善糖尿病合并非酒精性脂肪性肝病氧化应激损伤的机制

Exploration on the mechanism of improvement of oxidative stress injury in diabetes mellitus combined with nonalcoholic fatty liver disease by Shenqi Huatan Formula based on mitochondrial fusion-fission system

目的:观察参芪化痰方对糖尿病合并非酒精性脂肪性肝病(T2DM-NAFLD)模型大鼠的治疗作用,并基于线粒体融合-分裂系统探讨其作用机制。方法:采用STZ联合高脂饲料饲养8周诱导T2DM-NAFLD模型,将T2DM-NAFLD大鼠随机分为模型组、参芪化痰方组和西药(二甲双胍)组,各组灌胃相应药物。检测空腹血糖(FPG)、氧化应激指标,通过HE染色观察肝脏病理变化,透射电镜观察肝脏线粒体结构,Western Blot法检测与线粒体融合-分裂系统相关蛋白表达。结果:与模型组比较,参芪化痰方组大鼠FPG、丙二醛(MDA)水平显著降低(P<0.01,P<0.05),超氧化物岐化酶(T-SOD)水平显著上升(P<0.01),肝脏及线粒体病理损伤有所缓解。参芪化痰方组线粒体融合蛋白Mfn1、OPA1表达水平增加(P<0.01),而线粒体分裂蛋白Drp1、Fis1表达水平下降(P<0.01)。结论:参芪化痰方可调节血糖、抑制T2DM-NAFLD大鼠氧化应激、改善肝细胞线粒体病理损伤,其作用机制可能与调控线粒体融合-分裂系统有关。

Objective:To observe the therapeutic effect of Shenqi Huatan Formula on diabetic rats with nonalcoholic fatty liver disease(T2DM-NAFLD),and to explore its mechanism based on mitochondrial fusion-fission system.Methods:T2DMNAFLD model was induced by STZ combined with high-fat feed for 8 weeks.T2DM-NAFLD rats were randomly divided into model group,Shenqi Huatan Formula group and western medicine(Metformin)group,and each group was given corresponding drugs by gavage.Fasting plasma glucose(FPG)and oxidative stress were detected,pathological changes of liver were observed by HE staining,mitochondrial structure of liver was observed by transmission electron microscope,and protein expression related to mitochondrial fusion-division system was detected by Western Blot.Results:Compared with the model group,the levels of FPG and malondialdehyde(MDA)decreased(P<0.01,P<0.05),the level of superoxide dismutase(T-SOD)increased significantly(P<0.01),and the pathological damage of liver and mitochondria was alleviated.In Shenqi Huatan Formula group,the expression levels of mitochondrial fusion proteins Mfn1 and OPA1 increased(P<0.01),while the expression levels of mitochondrion proteins Drp1 and Fis1 decreased(P<0.01).Conclusion:Shenqi Huatan Formula regulates blood glucose,inhibits oxidative stress and ameliorates mitochondrial pathological damage in hepatocytes in T2DM-NAFLD rats,and its mechanism of action may be related to the modulation of the mitochondrial fusion-fission system.