首页> 中文期刊> 《现代中西医结合杂志》 >茶多酚通过TRB-3/AKT信号通路改善大鼠糖尿病肾病的分子机制

茶多酚通过TRB-3/AKT信号通路改善大鼠糖尿病肾病的分子机制

         

摘要

Objective It is to investigate the effect of tea polyphenols ( TP) on nephropathy rats and the impact of TP on TRB3/AKT signal pathway .Methods 50 male SD rats were divided into five groups randomly .The rats of control group were feed on an ordinary chow , and the rats of DN, TP low dose treatment group (250 mg/kg· day, n=10), TP middle dose treat-ment group(500 mg/kg· day, n=10) and TP high dose treatment group (1000 mg/kg· day, n=10) were fed with a high-fat diet, and after 4 weeks, those rats were injected with STZ solution (45 mg/kg), after the establishment of DN rats model , the rats of treatment group were administrated with TP by gavage , while the rats of model group received normal saline with the same method respectively once a day , 4 weeks later, all the rats were sacrificed, the blood and kidney tissues were harvested , the related factors like SCr , BUN, TG, TC, LDL-C, blood sugar , insulin were determined through ELISA , and mRNA and expression of TRB-3 and AKT were detected by RT-qPCR and Western Blot respectively .Results Compared with the control group, the concentrations of BUN , SCr, glucose, insulin, HOMA-IR,TG , TC and LDL-C in the serum of the rats of the mod-el group were increased, and decreased obviously after TP treatment for 4 weeks (P<0.05), furthermore, the effect of TP had a dose-dependent manner;Compared with the control group , the expression level of TRB 3 in the skeletal muscle tissues of model group were increased(P<0.05), after TP administration for 4 weeks, the expression levels of TRB-3 were decreased obviously(P<0.05), the phosphorylation levels of p-AKT(Thr308) and p-AKT( Ser47) were upregulated(P<0.05), all the effects of TP have a dose-dependent manner .Conclusion TP can ameliorate the renal function and dyslipidemia , moreover, TP is capable to alleviate IR and treat DN through regulating the TRB-3/AKT pathyway.%目的 观察茶多酚(TP)对糖尿病肾病(DN)大鼠的作用及对TRB-3/AKT信号通路的影响.方法 将50只雄性SD大鼠随机分为正常组、DN组、TP低剂量组、TP中剂量组以及TP高剂量组,每组10只.正常组给予普通饲料喂养,其余组给予高脂饲料喂养,4周后,除正常组外,其余组均进行链脲佐菌素(STZ,45 mg/kg)注射造模.造模成功后,TP低剂量组、TP中剂量组以及TP高剂量组分别给予TP 250 mg/(kg·d)、500 mg/(kg·d)、1000 mg/(kg·d)灌胃,正常组和DN组予以相同体积生理盐水灌胃,4周后处死大鼠,收集血清,检测血肌酐(SCr)、尿素氮(BUN)、血脂(TG、TC、LDL-C)、血糖、胰岛素水平,计算HOMA-IR;收集肾脏组织,分别采用RT-qPCR和Western blot方法检测TRB-3、AKT的mRNA和蛋白表达水平.结果 DN组大鼠血清BUN、SCr、血糖、胰岛素、HOMA-IR、TG、TC、LDL-C水平和肾脏组织中TRB-3的mRNA和蛋白表达水平均明显高于正常组(P均<0.05),TP各剂量组上述指标水平均明显低于DN组(P均<0.05),且具有剂量依赖性.各组AKT的mRNA和蛋白表达水平比较差异均无统计学意义(P均>0.05).DN组大鼠肾脏组织中p-AKT(Thr308位点)和p-AKT(Ser473位点)的磷酸化水平均明显低于正常组(P均<0.05),TP各剂量组均明显高于DN组(P均<0.05),且具有剂量依赖性.结论 TP可改善肾功能和脂质代谢紊乱,并通过调节TRB-3/AKT信号通路缓解胰岛素抵抗治疗DN.

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