紫苏叶多糖对糖尿病模型小鼠胰腺组织氧化应激及PI3K/AKT/GLUT4信号通路的影响

Effects of Purple frutescens Leaves Polysaccharides on Oxidative Stress and PI3K/AKT/GLUT4 Signaling Pathway of Pancreatic Tissues in Diabetes Mellitus Model Mice

目的:研究紫苏叶多糖对糖尿病(DM)模型小鼠胰腺组织氧化应激及磷酸肌醇-3-激酶(PI3K)/苏氨酸蛋白激酶(AKT)/葡萄糖转运蛋白4(GLUT4)信号通路的影响。方法:取60只小鼠,采用腹腔注射链脲佐菌素(60 mg/kg)的方法复制糖尿病模型。将造模成功的40只小鼠随机分为模型组、二甲双胍组(阳性对照,200 mg/kg)和紫苏叶多糖高、低剂量组(400、200 mg/kg),每组10只;另取10只健康小鼠作为正常组(生理盐水)。每天灌胃给药1次,连续给药28 d。实验期间,观察小鼠一般状况和体质量变化;进行口服葡萄糖耐量(OGTT)实验[测定灌胃40%葡萄糖溶液0、30、60、120 min后的空腹血糖(FBG)水平]。末次给药后,测定小鼠血糖相关指标[FBG、空腹胰岛素(FINS)和胰岛素敏感指数(ISI)、胰岛素抵抗指数(IRI)]、血脂相关指标[血清中高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、总胆固醇(TC)、三酰甘油(TG)]和氧化应激相关指标[胰腺组织中丙二醛(MDA)含量和超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)活性]的变化,并测定小鼠胰腺组织中PI3K、磷酸化AKT(p-AKT)和GLUT4蛋白表达水平。结果:实验期间,与正常组比较,模型组小鼠行动迟缓,饲料消耗量和饮水量增多,体质量显著增加(P<0.05);给予葡萄糖0、30、60、120 min后,小鼠的FBG水平均显著升高(P<0.05);末次给药后,血清中FINS、HDL-C含量和ISI以及胰腺组织中SOD、CAT、GSH-Px活性和PI3K、p-AKT、GLUT4蛋白表达水平均显著降低(P<0.05),而血清中FBG、LDL-C、TC、TG含量和IRI以及胰腺组织中MDA含量均显著升高(P<0.05)。与模型组比较,各给药组小鼠一般情况和OGTT情况均有好转;血清中FINS、HDL-C含量和ISI以及胰腺组织中SOD、CAT、GSH-Px活性和PI3K、p-AKT、GLUT4蛋白表达水平均显著升高(P<0.05),而血清中FBG、LDL-C、TC、TG含量和IRI以及胰腺组织中MDA含量均显著降低(P<0.05)。结论:紫苏叶多糖具有抗糖尿病作用,该作用可能与降低氧化应激水平和促进PI3K/AKT/GLUT4信号通路的活化有关。

OBJECTIVE:To study the effects of Purple frutescens leaves polysaccharides(PPLPs) on oxidative stress and PI3K/AKT/GLUT4 signaling pathway of pancreatic tissues in diabetes mellitus(DM) model mice. METHODS:Totally 60 mice were given intraperitoneal injection of STZ(60 mg/kg) to induce DM model. The 40 successful modeling mice were randomly divided into model group,metformin group(positive control,200 mg/kg),PPLPs high-dose and low-dose groups(400,200 mg/kg),with 10 mice in each group. Another 10 healthy mice were selected as the normal group(normal saline). They were given relevant medicine intragastrically,once a day,for consecutive 28 days. During the experiment,general information and body weight of mice were observed;oral glucose tolerance(OGTT)test(determining FBG at 0,30,60,120 min after giving 40%glucose solution) was conducted. After last medication,the changes of related blood glucose indexes(FBG,FINS,ISI,IRI),blood lipid indexes(HDL-C,LDL-C,TC,TG) and oxidant stress indexes(MDA content and the activities of SOD,CAT,GSH-Px)as well as the protein expressions of PI3K,p-AKT and GLUT4 in pancreatic tissue were determined. RESULTS:During the experiment,compared with normal group,the mice were slow in action,the feed consumption and water consumption increased,and body weight significantly increased in model group(P<0.05). 0,30,60,120 min after giving glucose,the FBG content of mice were all increased significantly(P<0.05). After last medication,the contents of FINS and HDL-C in serum as well as ISI,the activities of SOD,CAT and GSH-Px as well as the protein expressions of PI3K,p-AKT and GLUT4 in pancreatic tissue were all decreased significantly(P<0.05);the contents of FBG and LDL-C,TC and TG in serum as well as IRI,MDA content in pancreatic tissue were all increased significantly(P<0.05). Compared with model group,the general condition and OGTT of mice in each administration group was improved;the contents of FINS and HDL-C in serum as well as ISI,the activities of SOD,CAT and GSH-Px as well as the protein expressions of PI3K,p-AKT and GLUT4 in pancreatic tissue were all increased significantly(P<0.05);the contents of FBG,LDL-C,TC and TG in serum as well as IRI,MDA content of pancreatic tissue were decreased significantly(P<0.05).CONCLUSIONS:PPLPs has anti-diabetic effects,which are related to reducting oxidative stress level and promoting the activation of PI3K/AKT/GLUT4 signaling pathway.