探讨降糖消渴颗粒对高脂饮食诱导2型糖尿病肾脏氨基末端激酶信号通路的影响

Jiangtangxiaoke Granules on High Fat Diet Induced Type 2 Diabetic Kidney Amino Terminal Kinase Pathway

目的:运用降糖消渴颗粒治疗高脂饮食诱导2型糖尿病并探讨其对肾脏氨基末端激酶信号通路的影响。方法:72只Wistar大鼠,在SPF级条件下饲养,根据随机数字表法分为干预组、对照组和正常对照组,每组24只,通过链脲佐菌素(STZ)30 mg/kg腹腔注射协同高脂饮食诱导2型糖尿病进行动物造模,造模后干预,正常对照组予标准饲料;对照组予高糖高脂饲料;干预组予高糖高脂饲料,降糖消渴颗粒根据大鼠体重9 g/kg的计算灌胃剂量,1次/d。疗程8周。采用酶联免疫吸附测定法(ELISA法)检测大鼠的血糖(Glu)、三酰甘油(TG),总胆固醇(TC)、血肌酐(Scr);常规HE染色,观察各组肾脏结构变化;实时荧光聚合酶链式反应(q-PCR)检测肾组织中氨基末端激酶(JNK)和胰高血糖样肽-1(GLP-1)mRNA的表达,蛋白质印迹法(Western Blot)检测肾组织中JNK信号通路的激活情况情况,JNK、磷酸化氨基末端激酶(p-JNK)和GLP-1的蛋白表达情况。结果:1)干预组经治疗后Glu、TC、TG和Scr较对照组显著下降(P<0.05)。2)干预组较对照组明显改善肾小球结构改变的情况(P<0.05)。3)与正常对照组比较,对照组中p-JNK蛋白表达显著升高(P<0.05),GLP-1基因和蛋白显著降低(P<0.05);经治疗后干预组p-JNK蛋白较对照组降低(P<0.05),而GLP-1基因和蛋白升高(P<0.05)。结论:降糖消渴颗粒可调节糖、脂质代谢,发挥保护肾脏作用,其作用机制可能与抑制JNK信号通路,上调GLP-1有关。

Objective： To study the Jiangtangxiaoke granule in the treatment of high fat diet induced type 2 diabetes and to investi- gate its effect on renal N-terminal kinase signal pathway. Methods： All 72 Wistar rats were reared in SPF conditions, and were randomly divided into an intelwention group, a control group and a normal control group, 24 rats in each. By streptozotocin （STZ） intraperitoneal injection of 30 mg/kg synergy, high fat diet induced type 2 diabetes animal models were built. After the model in- tervention, the normal control group received standard diet; the control group was treated with high glucose and high fat diet; the intervention group treated with high glucose, high fat diet, and Jiangtangxiaoke granules were calculated according to the body weight of 9 g/kg rats by garage once daily. Treatment lasted 8 weeks. Using enzyme-linked immunosorbent assay （ELISA meth- od） to detect rats blood glucose （Glu）, triglyceride （TG）, total cholesterol （TC） , serum creatinine （Scr） ; routine HE staining, observing the changes of renal structure in each group ; real time fluorescent polymerase chain reaction （q-PCR） detection （ amino terminal kinase） and JNK （ glucagon like peptide-I GLP-1 ） and Western blotting （ Western Blot） to detect the activation of JNK signaling pathway, JNK （phosphorylated N-terminal kinase） p-JNK and GLP-1. Results： i ） The Glu, TC, TG and Scr in the in- tervention group were significantly lower than those in the control group （ P 〈 0. 05 ）. 2） Compared with the control group, the changes of glomerular structure were significantly improved in the intervention group （ P 〈 0. 05 ）. 3 ） Compared with the normal control group, the expression of p-JNK protein in control group increased significantly （P 〈 0.05 ） , GLP-1 gene and protein signif- icantly decreased （ P 〈 0. 05 ） ; after treatment, the intervention group of p-JNK protein was lower than that of the control group （ P 〈 0. 05）, and GLP-1 （P 〈 0. 05 ） gene and protein increased. Conclusion： Jiangtangxiaoke granules can regulate sugar, lipid metabolism, protect the kidney function, its mechanism may be related to the inhibition of the JNK signaling pathway and regulation of GLP-1.