摘要
目的 观察糖肾灌肠方联合缬沙坦对2型糖尿病肾病的疗效及对大鼠肾脏组织Toll样受体 2(Toll-like receptor 2,TLR2)、Toll 样受体 4(Toll-like receptor 4,TLR4)表达的影响.方法 选取无特定病原体(Specific pathogen free,SPF)级8周龄SD雌性大鼠60只,适应性喂养7 d后,随机选取10只作为空白对照组,其余50只进行右侧肾脏摘取手术,构建2型糖尿病肾病大鼠模型.造模过程中死亡10只,造模成功的40只大鼠随机分为模型组、糖肾灌肠方干预组(糖肾灌肠方0.13 mL/10 g)、缬沙坦干预组(缬沙坦0.12 mg/10 g,)、缬沙坦+糖肾灌肠方干预组(糖肾灌肠方0.13 mL/10 g联合缬沙坦0.12 mg/10 g),每天1次,连续灌肠4周.观察5组大鼠空腹血糖水平,肾组织形态学改变情况,尿蛋白、尿素氮(Urea nitrogen,BUN)及肌酐(Creatinine,Cr)水平,肾湿质量及肾脏肥大指数,TLR2、TLR4信使核糖核酸(Messenger RNA,mRNA)及蛋白表达情况.结果 与空白对照组比较,各造模组血糖和尿蛋白含量均显著升高(P＜0.05);与模型组比较,糖肾灌肠、缬沙坦干预组与缬沙坦+糖肾灌肠方干预组的血糖降低但差异无统计学意义(P＞0.05),糖肾灌肠方干预组、缬沙坦片干预组及缬沙坦+糖肾灌肠方干预组的尿蛋白含量下降(P＜0.05),且缬沙坦+糖肾灌肠方干预组的尿蛋白含量显著下降(P＜0.05).与空白对照组比,模型组肾组织病变显著,如肾小管扩张、纤维化、炎性细胞浸润及坏死细胞脱落;与模型组比较,糖肾灌肠干预方组和缬沙坦片干预组的大鼠肾小管扩张程度、炎性细胞浸润及坏死细胞脱落情况有所减轻,缬沙坦+糖肾灌肠方干预组的大鼠肾小管基本无扩张,仅有少量炎性细胞浸润及坏死细胞脱落,肾脏结构更接近空白对照组.与空白对照组比较,模型组的血清Cr含量、粪便Cr含量、血清BUN含量、血/粪BUN比值、肾湿重、肾肥大指数、TLR2mRNA、TLR4mRNA、TLR2蛋白及TLR4蛋白表达均显著升高(P＜0.05);与模型组比较,糖肾灌肠方干预组、缬沙坦干预组及缬沙坦+糖肾灌肠方干预组以上指标均下降(P＜0.05),且缬沙坦+糖肾灌肠方干预组的降幅最大.结论 糖肾灌肠方联合缬沙坦治疗2型糖尿病肾病效果更佳,并能抑制大鼠肾脏组织TLR2、TLR4表达,因此值得在临床上推广应用.
Abstract
Objective To observe the effect of Tangshen enema formula combined with valsartan on type 2 diabetic nephropathy and the expression of toll like receptor 2(TLR2)and C(TLR4)in kidney tissue of rats.Methods 60 8-week-old female SD rats without specific pathogen free(SPF)were selected.After adaptive feeding for 7 days,10 rats were randomly selected as blank control group,and the other 50 rats underwent right kidney extraction surgery to construct the rat model of type 2 diabetic nephropathy.10 rats died during the modeling process.40 rats with successful modeling were randomly divided into model group,Tangshen enema group(Tangshen enema 0.13 ml/10 g),valsartan intervention group(valsartan 0.12 mg/10g),valsartan+Tangshen enema group(Tangshen enema 0.13 ml/10g combined with valsar-tan 0.12 mg/10 g),once a day for 4 weeks.The blood glucose level,renal histomorphological changes,urinary protein,urea nitrogen(BUN)and creatinine(CR)levels,renal wet weight and renal hypertrophy index,TLR2,TLR4 messenger RNA(mRNA)and protein expression were observed in the 5 groups.Re-sults Compared with blank control group,the levels of blood glucose and urinary protein in each model group were significantly increased(P＜0.05);Compared with model group,the blood glucose of Tangsh-en enema,valsartan intervention group and valsartan+Tangshen enema formula intervention group was decreased,but the difference was not statistically significant(P＞0.05).The urinary protein content of Tangshen enema formula intervention group,valsartan tablets intervention group and valsartan+Tangsh-en enema formula intervention group was decreased(P＜0.05),and the urinary protein content of valsar-tan+Tangshen enema formula intervention group was decreased significantly(P＜0.05).Compared with blank control group,the renal tissue lesions in the model group were significant,such as renal tubular ex-pansion,fibrosis,inflammatory cell infiltration and necrotic cell shedding;Compared with model group,the degree of renal tubule expansion,inflammatory cell infiltration and necrotic cell shedding in the Tang-shen enema intervention group and valsartan tablets intervention group were reduced,while the renal tu-bules in the Valsartan+Tangshen enema intervention group had no expansion,only a small amount of in-flammatory cell infiltration and necrotic cell shedding,and the renal structure was closer to the blank con-trol group.Compared with blank control group,the serum Cr content,fecal Cr content,serum BUN con-tent,blood/fecal bun ratio,renal wet weight,renal hypertrophy index,TLR2mRNA,TLR4mRNA,TLR2 protein and TLR4 protein expression in the model group were significantly was increased(P＜0.05);Compared with model group,the above indexes in Tangshen enema formula intervention group,valsartan intervention group and valsartan+Tangshen enema formula intervention group was decreased(P＜0.05),and the decrease in valsartan+Tangshen enema formula intervention group was the largest.Conclusion Tangshen enema formula combined with valsartan has better effect in the treatment of type 2 diabetic nephropathy,and it can inhibit the expression of TLR2 and TLR4 in rat kidney tissue,so it is worthy of clinical application.
基金项目
新疆维吾尔自治区自然科学基金(2020D01C133)
维普
万方数据