补阳还五汤调控丝裂原活化蛋白激酶信号通路对2型糖尿病大鼠糖脂代谢的影响

Effects of BuyangHuanwu Decoction on Glucose and Lipid Metabolism in Type 2 Diabetic Rats by Regulating Mitogen-activated Protein Kinase Signaling Pathway

目的观察补阳还五汤调控丝裂原活化蛋白激酶(MAPK)信号通路对2型糖尿病(T2DM)大鼠糖脂代谢的影响。方法选取Wistar大鼠60只,随机分为空白组、模型组、阳性对照组及补阳还五汤低、中、高剂量组,每组10只。空白组予基础饲料,其余5组大鼠予高脂饲料喂养,制备T2DM模型。造模成功后,补阳还五汤低、中、高剂量组分别予补阳还五汤药液1.6、3.2、6.4 g/kg生药灌胃,阳性对照组予二甲双胍片混悬液0.2 g/kg生药灌胃,空白组、模型组均予等容积0.9%氯化钠注射液灌胃,持续给药12周。比较各组大鼠体质量、饮水量、摄食量和尿量,空腹血糖(FPG)、空腹胰岛素(FINS)、糖化血红蛋白(HbA_(1)c)水平,总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平;观察各组大鼠肝脏组织病理学变化,MAPK、磷酸化MAPK(p-MAPK)蛋白表达以及肝脏组织MAPK mRNA、成纤维细胞生长因子21(FGF21)mRNA表达。结果补阳还五汤可明显改善T2DM大鼠体质量、12 h饮水量、摄食量、尿量,FPG、FINS、HbA_(1)c水平,TC、TG、LDL-C、HDL-C水平(P<0.05),随着补阳还五汤剂量增加,大鼠体质量递增,12 h饮水量、摄食量、尿量,FPG、FINS、HbA_(1)c水平,TC、TG、LDL-C水平均递减,HDL-C水平递增。补阳还五汤各剂量组大鼠肝脏组织均在不同程度上有明显改善,且高剂量组效果最显著。补阳还五汤可明显改善T2DM大鼠MAPK、p-MAPK蛋白,MAPK mRNA、FGF21 mRNA表达(P<0.05),随着补阳还五汤剂量增加,MAPK、p-MAPK蛋白,MAPK mRNA、FGF21 mRNA表达均递增。结论补阳还五汤可有效改善T2DM大鼠糖脂代谢,其作用机制可能与激活MAPK信号通路有关。

Objective To investigate the effect of BuyangHuanwu Decoction on glucose and lipid metabolism in type 2 diabetes mellitus(T2DM)rats by regulating mitogen-activated protein kinase(MAPK)signaling pathway.Methods Sixty Wistar rats were selected and randomly divided into blank group,model group,positive control group,BuyangHuanwu Decoction low-,middle-and high-dose groups,with 10 rats in each group.Except for the blank group(basic feed feeding),the rats in the other groups were fed with high-fat diet to prepare T 2 DM model.After successful modeling,the low,medium and high dose groups were given gastric irrigation of BuyangHuanwu Decoction 1.6,3.2 and 6.4 g/kg respectively.The positive control group was given gastric irrigation of metformin tablet suspension 0.2 g/kg.The blank group and the model group were given gastric irrigation of equal volume of 0.9%sodium chloride injection,and the continuous administration performed for 12 weeks.The body weight and survival status of the rats in each group were observed;enzyme-linked immunosorbent assay and biochemical analyzer were used to determine the blood glucose and blood lipid levels of the rats in each group;the pathological morphology of the rat liver was observed;WB and PCR were used to determine the MAPK signaling pathway-related proteins and genes The expression level.The body weight,water intake,food intake and urine volume,fasting blood glucose(FPG),fasting insulin(FINS),glycosylated hemoglobin(HbA 1c),total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C)and high density lipoprotein cholesterol(HDL-C)were compared among the groups.The expression of MAPK,phosphorylated MAPK(p-MAPK)protein,MAPK mRNA,and fibroblast growth factor 21(FGF21)mRNA in liver tissue were observed.Results BuyangHuanwu Decoction can significantly improve the body mass,12 h water intake,food intake,urine output,FPG,FINS,HbA 1c levels,TC,TG,LDL-C,and HDL-C levels of T2DM rats(P<0.05).As the dosage of BuyangHuanwu Tang increases,the body mass of rats increases.The levels of 12h water intake,food intake,urine output,FPG,FINS,HbA 1c,TC,TG,LDL-C levels all decreased,while HDL-C levels increase.The liver tissue of rats of BuyangHuanwu Decoction groups showed significant improvement to varying degrees,and the high-dose group had the most significant effect.BuyangHuanwu Decoction can significantly improve the expression of MAPK,p-MAPK protein,MAPK mRNA,and FGF21 mRNA in T2DM rats(P<0.05).As the dosage of BuyangHuanwu Decoction increases,the expression of MAPK,p-MAPK protein,MAPK mRNA,and FGF21 mRNA increases.Conclusion BuyangHuanwu Decoction can effectively improve glucose and lipid metabolism in T2DM rats,and its mechanism may be related to the activation of MAPK signaling pathway.