桑叶提取物基于PI3K/AKT通路对2型糖尿病大鼠的作用研究

Effect of mulberry leaf extract based on PI3K/AKT pathway in type 2 diabetes mellitus rats

目的分析桑叶提取物基于磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)通路对2型糖尿病大鼠的作用。方法将桑叶风干后粉碎成粉末,萃取、洗涤、洗脱并室温蒸发下得到干燥提取物。选取46只SPF级SD大鼠,随机选取10只大鼠作为空白组,另外36只建立2型糖尿病模型。采用腹腔一次性注射40 mg/kg链脲佐菌素建立2型糖尿病模型。将建模成功30只大鼠按照随机数字表法分为模型组、低剂量组、高剂量组,各10只。空白组、模型组大鼠注射相同剂量的0.9%氯化钠溶液,低剂量组大鼠给予0.1 mL/100 g桑叶提取物,高剂量组大鼠给予0.4 mL/100 g桑叶提取物;空白组喂普通饲料,模型组、低剂量组、高剂量组喂高脂高糖饲料。观察大鼠一般情况和病理形态;比较大鼠的空腹血糖(FBG)、血脂[甘油三酯、总胆固醇、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)]、胰岛素水平及HOMA-IR指数、生化指标[超氧化物岐化酶(SOD)、总抗氧化能力(T-AOC)、丙二醛]水平,并比较PI3K、AKT mRNA表达量以及PI3K/AKT通路蛋白表达量。结果与空白组相比,模型组、低剂量组、高剂量组的FBG、胰岛素、甘油三酯、总胆固醇、LDL-C、丙二醛水平、HOMA-IR指数、PI3K、AKT mRNA表达量、PI3K、p-PI3K、AKT、p-AKT表达量升高,HDL-C、SOD、T-AOC水平降低,差异均有统计学意义(P<0.05)。与模型组相比,低剂量组和高剂量组的FBG、胰岛素、甘油三酯、总胆固醇、LDL-C、丙二醛水平、HOMA-IR指数、PI3K、AKT mRNA表达量、PI3K、p-PI3K、AKT、p-AKT表达量降低,HDL-C、SOD、T-AOC水平升高,差异均有统计学意义(P<0.05)。与低剂量组相比,高剂量组的FBG、胰岛素、甘油三酯、总胆固醇、LDL-C、丙二醛水平、HOMA-IR指数、PI3K、AKT mRNA表达量、PI3K、p-PI3K、AKT、p-AKT表达量降低,HDL-C、SOD、T-AOC水平升高,差异均有统计学意义(P<0.05)。结论桑叶提取物可改善2型糖尿病大鼠胰腺病理变化,降低FBG水平,改善血脂、SOD、T-AOC、丙二醛水平,抑制PI3K、AKT表达。

Objective To analyze the effect of mulberry leaf extracts was performed based on the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway in type 2 diabetes mellitus rats.Methods After drying the mulberry leaves,they were crushed into powder,extracted,washed,eluted,and evaporated at room temperature to obtain a dry extract.Among 46 SPF SD rats,10 rats were selected as blank group,and another 36 established type 2 diabetes mellitus model.The model of type 2 diabetes mellitus was established by intraperitoneal injection of 40 mg/kg streptozotocin.Thirty rats were divided into model group,low-dose group,high-dose group,10 each,0.1 mL/100 g mulberry leaf extract in the low-dose group,0.4 mL/100 g mulberry leaf extract,and model group,low-dose group and high-dose group.The general condition and pathological morphology of rats were observed.Fasting blood glucose(FBG),blood lipids[triglyceride,total cholesterol,low density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C)],insulin level,HOMA-IR index,biochemical indicators[superoxide dismutase(SOD),total antioxidant capacity(T-AOC),malondialdehyde]levels of rats were compared,and PI3K,AKT mRNA expression and PI3K/AKT pathway protein expression were compared.Results Compared with the blank group,the levels of FBG,insulin,triglyceride,total cholesterol,LDL-C,malondialdehyde,HOMA-IR index,PI3K,AKT mRNA expression,PI3K,p-PI3K,AKT,p-AKT expression in the model group,low-dose group and high-dose group were increased,and the levels of HDL-C,SOD,T-AOC were decreased,the differences were statistically significant(P<0.05).Compared with the model group,the levels of FBG,insulin,triglyceride,total cholesterol,LDL-C,malondialdehyde,HOMA-IR index,PI3K,AKT mRNA expression,PI3K,p-PI3K,AKT,p-AKT expression in the low-dose group and high-dose group were decreased,and the levels of HDL-C,SOD,T-AOC were increased,the differences were statistically significant(P<0.05).Compared with the low-dose group,the levels of FBG,insulin,triglyceride,total cholesterol,LDL-C,malondialdehyde,HOMA-IR index,PI3K,AKT mRNA expression,PI3K,p-PI3K,AKT,p-AKT expression in the high-dose group were decreased,and the levels of HDL-C,SOD,T-AOC were increased,the differences were statistically significant(P<0.05).Conclusion Mulberry leaf extract can improve pancreatic pathological changes in type 2 diabetes mellitus rats,reduce FBG levels,improve blood lipids,SOD,T-AOC,malondialdehyde levels,and inhibit the expression of PI3K and AKT.