刺梨对肥胖大鼠胰岛素抵抗的干预作用及其机制

Effects of Rosa roxburghii on insulin resistance in obese rats and its mechanisms

目的:研究刺梨对肥胖大鼠胰岛素抵抗的干预作用以及磷脂酰肌醇3激酶(PI3K)/蛋白激酶Bβ(PKBβ/Akt2)/葡萄糖转运蛋白4(GLUT4)信号通路在其中的调控作用。方法:5周龄雄性SD大鼠随机分为正常对照组(NC)、模型组(M)、西格列他钠阳性对照组(PC)、低剂量刺梨组(LD)和高剂量刺梨组(HD),每组10只。NC组以普通饲料喂养,M、PC、LD和HD组以高脂饲料喂养。第13周开始,按照6 ml/kg的剂量标准,LD组以100 mg/kg刺梨灌胃,HD组以300 mg/kg刺梨灌胃,PC组以0.11 g/kg西格列他钠灌胃,NC组、M组以等体积的生理盐水灌胃。实验直至20周,每周测量大鼠体质量,末次实验结束后24 h处死大鼠,取血液和骨骼肌,比色法检测血清总胆固醇(TC)、甘油三酯(TG)含量,黄嘌呤氧化酶法检测血清超氧化物歧化酶(SOD)活性,硫代巴比妥酸法检测血清丙二醛(MDA)含量,葡萄糖氧化酶法检测血糖(FBG)值,酶联免疫吸附法检测胰岛素(FINS)含量,蛋白免疫印迹和逆转录-聚合酶链反应法检测PI3K、Akt2、GLUT4蛋白、基因表达。结果:与NC组比较,M组体质量、血清MDA、TG、TC、FBG、FINS、HOMA-IR水平显著升高(P<0.01),SOD活性、PI3K、Akt2、GLUT4蛋白和mRNA表达水平显著降低(P<0.01)。与M组比较,LD组、HD组和PC组体质量、血清MDA、TG、TC、FBG、FINS、HOMA-IR水平均显著降低(P<0.05或P<0.01),SOD活性、PI3K、Akt2、GLUT4蛋白和mRNA表达水平均显著升高(P<0.05或P<0.01)。结论:刺梨可通过抗氧化应激以及上调PI3K、Akt2、GLUT4蛋白、基因的表达改善肥胖大鼠胰岛素抵抗,其分子机制可能与PI3K/Akt2/GLUT4信号通路有关。

Objective:To investigate the effects of Rosa roxburghii on insulin resistance in obese rats and the regulation of phosphatidylinositol 3-kinase(PI3K)/protein kinase Bβ(PKBβ/Akt2)/glucose transporter 4(GLUT4)signaling pathway.Methods:Five-week-old male SD rats were randomly divided into normal control group(NC),model group(M),positive control group(PC),low-dose rosa roxburghii group(LD)and high-dose rosa roxburghii group(HD),with 10 rats in each group.The rats in the NC group were fed with normal diet,while those in the M,PC,LD and HD groups were fed with high-fat diet.From the 13th week,according to the dose standard of 6 ml/kg,rats in the LD group were intragastrically administered with 100 mg/kg Rosa roxburghii Tratt,the HD group were treated with 300 mg/kg Rosa roxburghii Tratt,the PC group were treated with 0.11 g/kg Chiglitazar sodium,and the NC and M groups were intragastrically administered with the same volume of normal saline.The body weight was measured every week until 20 weeks.The rats were sacrificed 24 h after the last experiment.Blood and skeletal muscle were collected.Serum total cholesterol(TC)and triglyceride(TG)contents were detected by colorimetric method,serum superoxide dismutase(SOD)activity was detected by xanthine oxidase method,serum malondialdehyde(MDA)content was detected by thiobarbituric acid method,blood glucose(FBG)value was detected by glucose oxidase method,insulin(FINS)content was detected by ELISA,and PI3K,Akt2,and GLUT4 protein and gene expressions were detected by Western blot and reverse transcription-polymerase chain reaction(RT-PCR).Results:Compared with the NC group,the body weight,serum MDA,TG,TC,FBG,FINS,HOMA-IR levels in the M group were significantly increased(P<0.01),while SOD activity,PI3K、Akt2、GLUT4 protein and mRNA expression levels were significantly increased(P<0.01).Compared with group M,the body weight,serum MDA,TG,TC,FBG,FINS,and HOMA-IR were decreased significantly in LD group,HD group and PC group(P<0.05 or P<0.01),while SOD activity,PI3K,Akt2,GLUT4 protein and mRNA expression levels were increased significantly(P<0.05 or P<0.01).Conclusion:Rosa roxburghii can improve insulin resistance in obese rats by antioxidant stress and up-regulating the expressions of PI3K,Akt2,and GLUT4 proteins and genes,which may be related to the PI3K/Akt2/GLUT4 signaling pathway.