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。
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 608-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 valsartan 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.Results 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 Tangshen 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+Tangshen enema formula intervention group was decreased(P<0.05),and the urinary protein content of valsartan+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 expansion,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 Tangshen enema intervention group and valsartan tablets intervention group were reduced,while the renal tubules in the Valsartan+Tangshen enema intervention group had no expansion,only a small amount of inflammatory cell infiltration and necrotic cell shedding,and the renal structure was closer to the blank control group.Compared with blank control group,the serum Cr content,fecal Cr content,serum BUN content,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.
作者
李晶
冯涛
陈晨
马丽
LI Jing;FENG Tao;CHEN Chen;MA Li(Department of Endocrinology,Affiliated Traditional Chinese Medicine Hospital of Xinjiang Medical University,Urumqi 830000,China;Department of General Surgery,Affiliated Traditional Chinese Medicine Hospital of Xinjiang Medical University,Urumqi 830000,China)
出处
《新疆医科大学学报》
CAS
2024年第4期594-601,共8页
Journal of Xinjiang Medical University
基金
新疆维吾尔自治区自然科学基金项目(2020D01C133)。
关键词
糖肾灌肠方
缬沙坦
糖尿病肾病
炎症因子
Tangshen enema formula
valsartan
diabetic nephropathy
inflammatory factor
