津力达对胰岛素抵抗大鼠糖脂代谢紊乱及对PPARα/ABCA1通路的影响

Effect of Jinlida on Glucose and Lipid Metabolism Disorder in Insulin Resistant Rats and PPARα/Influence of ABCA1 Pathway

目的探讨津力达对胰岛素抵抗大鼠糖脂代谢紊乱改善作用及其相关机制研究。方法选取60只SD大鼠随机分为正常组、模型组,正常组给予普通大鼠饲料,模型组给予高糖高脂饲料喂养,喂养8周后,制备胰岛素抵抗模型,造模成功后选取符合要求的40只大鼠,随机分为模型组、津力达低剂量组、津力达高剂量组、二甲双胍组各10只,给予药物干预。末次给药后,各组大鼠口服灌胃葡萄糖,分别在0 min、30 min、60 min、120 min测量大鼠尾静脉血糖值,计算糖耐量曲线下面积,处死大鼠后检测生化指标、胰岛素抵抗指数、胰岛素敏感指数,进行肝脏苏木青染色(HE)染色,利用免疫蛋白印迹法(Western blot)方法检测肝脏三磷酸腺苷结合盒转运蛋白1(ABCA1)及其相关蛋白过氧化物酶体增殖物激活受体α(PPARα)、肝X受体α(LXRα)表达。结果与模型组相比,给药组降低空腹血糖(FBG)、口服糖耐量试验曲线下面积(OGTT-AUC)(P<0.05);津力达低、高剂量组和二甲双胍组可显著降低胰岛素抵抗指数(HOMA-IR)水平,增加胰岛素敏感性(HOMA-ISI)(P<0.05);与模型组相比,津力达低、高剂量组和二甲双胍组可明显降低血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)、游离脂肪酸(FFA)水平(P<0.05);津力达低、高剂量组可升高血清高密度脂蛋白(HDL-C);与模型组相比,津力达低、高剂量组、二甲双胍组肝脏结构清晰、肝细胞排列清楚、炎性细胞减少、空泡变少;与模型组相比,津力达低剂量组肝脏PPARα蛋白明显上调,津力达低、高剂量组、二甲双胍组肝脏LXRα蛋白表达明显上调;津力达低、高剂量组肝脏ABCA1蛋白表达明显上调(P<0.05)。结论津力达可有效改善大鼠糖脂代谢紊乱、增加胰岛素敏感性、改善胰岛素抵抗;津力达调节糖脂代谢紊乱及胰岛素抵抗作用可能与上调ABCA1,激活PPARα/ABCA1信号通路有关。

Objective To investigate the effect of Jinlida on glucolipid metabolism disorder and its related mechanism in insulin resistant rats.Methods Select 60 SD rats were randomly divided into normal group,model group,normal group gives ordinary feed rats.After 8 weeks of feeding,insulin resistance model was prepared.After successful modeling,40 rats meeting the requirements were selected and randomly divided into model group,Jinlida low-dose group,Jinlida high-dose group and metformin group with 10 rats in each group.Medication intervention was given.After the last administration,glucose was orally administered to rats in each group,and the glucose tolerance area under the curve was calculated at 0min,30min,60min and 120min,respectively.Biochemical indexes,insulin resistance index and insulin sensitivity index of rats were detected after death,and hematoxylin staining(HE)of liver was performed.Western Blot was used to detect the expression of adenosine triphosphate binding box transporter 1(ABCA1)and its related proteins,peroxisomal proliferator-activated receptorα(PPARα)and liver X receptorα(LXRα).Results Compared with model group,fasting blood glucose(FBG)and area under the curve of oral glucose tolerance test(OGTT-AUC)were decreased in administration group(P<0.05).The levels of insulin resistance index(HOMA-IR)and insulin sensitivity(HOMA-ISI)were significantly decreased in Jinlida low-dose and high-dose groups and metformin group(P<0.05).Compared with model group,the serum levels of total cholesterol(TC),triglyceride(TG),low-density lipoprotein(LDL-C)and free fatty acid(FFA)in Jinlida low-dose and high-dose groups and metformin group were significantly decreased(P<0.05);The serum high density lipoprotein(HDL-C)could be increased in the low and high dose groups.Compared with the model group,the liver structure was clear,liver cells were arranged clearly,inflammatory cells were reduced and vacuoles were reduced in the Jinlida low-dose,high-dose and metformin groups.Compared with model group,liver PPARαprotein was significantly up-regulated in Jinlida low-dose group,and LXRαprotein expression was significantly up-regulated in Jinlida low-dose,high-dose and metformin groups.The expression of ABCA1 protein in liver of Jinlida low and high dose groups was significantly up-regulated(P<0.05).Conclusion Jinlida can effectively improve glucose and lipid metabolism disorder,increase insulin sensitivity and improve insulin resistance in rats.The effect of Jinlida on glucolipid metabolism and insulin resistance may be related to up-regulation of ABCA1 and activation of PPARα/ABCA1 signaling pathway.