刺五加多糖对糖尿病大鼠代谢功能的影响及作用机制

Effect and Mechanism of Acanthopanax senticosus Polysaccharides on Metabolic Function in Diabetic Rats

目的探讨刺五加多糖对糖尿病大鼠代谢功能的影响及作用机制.方法尾静脉注射链脲佐菌素联合高脂饮食制备2型糖尿病大鼠模型,随机分为模型组、刺五加多糖低剂量组(60 mg/kg)、中剂量组(120 mg/kg)、高剂量组(240 mg/kg);另设置普通饲料喂养的大鼠为对照组.连续给药6周后观察大鼠的一般状况,腹主动脉取血,检测空腹血糖、糖化血红蛋白、血脂指标、超氧化物歧化酶(Superoxide dismutase,SOD)、过氧化氢酶、谷胱甘肽过氧化物酶、丙二醛水平.取血后迅速分离肝脏组织,进行HE染色;采用Western blot检测葡萄糖转运蛋白4(Glucose transporter 4,GLUT-4)、胰岛素受体底物2(Insulin receptor substrate 2,IRS-2)、过氧化物酶体增殖物激活受体γ(Peroxisome proliferator-activated receptor-γ,PPAR-γ)、磷脂酰肌醇3-激酶(Phosphatidylinositol 3-kinase,PI3K)、磷酸化Akt蛋白表达水平.结果与模型组大鼠比较,刺五加多糖中、高剂量组大鼠体质量明显增加,差异具有统计学意义(P<0.05);刺五加多糖各剂量组大鼠12 h饮水量、尿量、进食量均明显降低,差异具有统计学意义(P<0.05).与模型组大鼠比较,刺五加多糖中、高剂量组大鼠空腹血糖、糖化血红蛋白、甘油三酯、总胆固醇、低密度脂蛋白水平明显降低,高密度脂蛋白水平明显升高;刺五加多糖低、中、高剂量组大鼠SOD、过氧化氢酶、谷胱甘肽过氧化物酶水平明显升高,丙二醛水平明显降低.上述差异均具有统计学意义(P<0.05).与模型组大鼠比较,刺五加多糖中、高剂量组GLUT-4、IRS-2、PPAR-γ、PI3K、磷酸化Akt蛋白表达水平明显升高,刺五加多糖低剂量组GLUT-4、PPAR-γ蛋白表达水平明显升高,差异具有统计学意义(P<0.05).结论刺五加多糖在改善2型糖尿病大鼠糖脂代谢中疗效确切,激活IRS-2/PI3K/磷酸化Akt信号通路和上调GLUT-4和PPAR-γ表达是其作用机制之一.

Objective To investigate the effect of Acanthopanax senticosus polysaccharides on metabolic function and its mechanism in diabetic rats.Method The rat model of type 2 diabetes mellitus was established by tail injection of streptozotocin combined with high-fat diet.The rats were randomly divided into model group,low-dose Acanthopanax senticosus polysaccharide group(60 mg/kg),medium-dose Acanthopanax senticosus polysaccharide group(120 mg/kg)and high-dose Acanthopanax senticosus polysaccharide group(240 mg/kg).The rats fed with normal diet were set as control group.After 6 weeks of continuous administration,the general condition of rats was observed.Blood samples were taken from abdominal aorta to detect the levels of fasting blood glucose,glycosylated hemoglobin,fasting insulin,blood lipid index,superoxide dismutase(SOD),catalase,glutathione peroxidase and malondialdehyde.Western blot was used to detect the expression of glucose transporter 4(GLUT-4),insulin receptor substrate 2(IRS-2),peroxisome proliferator activated receptor gamma(PPAR-γ),phosph-atidylinositol 3-kinase(PI3K)and phosphorylated Akt protein.Results Compared with the model group,the body weight of rats in medium and high dose groups of Acanthopanax senticosus polysaccharide increased significantly(P<0.05);The amount of drinking water,urine and food intake of rats in low,medium and high dose groups of Acanthopanax senticosus polysaccharide decreased significantly(P<0.05).Compared with the model group,the levels of fasting blood glucose,glycosylated hemoglobin,triglyceride,total cholesterol and low-density lipoprotein significantly decreased,while the levels of high-density lipoprotein significantly increased in the medium and highdose Acanthopanax senticosus polysacchar groups(P<0.05).The levels of SOD,catalase and glutathione peroxidase in low,medium and high dose Acanthopanax senticosus polysacchar groups significantly increased,while the level of malondialdehyde significantly decreased(P<0.05).Compared with the model group,the protein expression levels of GLUT-4,IRS-2,PPAR-γ,PI3K and phosphorylated Akt in the medium and high dose groups of Acanthopanax senticosus polysacchar significantly increased,and the protein expression levels of GLUT-4 and PPAR-γin the low dose group of Acanthopanax senticosus polysacchar significantly increased(P<0.05).Conclusion Acanthopanax senticosus polysacchar has a definite effect on improving glucose and lipid metabolism in type 2 diabetic rats.One of its mechanisms is to activate IRS-2/PI3K/phosphorylated Akt signaling pathway and up-regulate the expression of GLUT-4 and PPAR-γ.