糖克煎剂对糖尿病肾病大鼠肾脏miR-192信号通路的影响

Effects of Tangke Decoction on miR-192 signaling pathway in diabetic nephropathy rats

目的:探讨糖克煎剂对糖尿病肾病大鼠肾脏miR-192信号通路的影响。方法:大鼠一次性尾静脉注射链脲佐菌素30mg/kg建立糖尿病模型,随机分为模型组、糖克煎剂4.5g/kg预防组、糖克煎剂4.5g/kg、18g/kg剂量组、福辛普利钠片组(0.9mg/kg),选取同龄大鼠作为正常对照组。测定血糖、24h尿蛋白、左肾重、肾重/体重比、BUN、Scr、TC、TG水平,HE染色观察肾脏组织病理变化,QRT-PCR法检测肾组织TGF-β1、miR-192、SIP1、Col1a2 m RNA的表达,Western-blot法检测肾脏中TGF-β1、SIP1、Collagen I蛋白的表达。结果:与模型组相比,糖克煎剂4.5g/kg预防组、糖克煎剂4.5g/kg、18g/kg剂量组和福辛普利钠片组24h尿蛋白量、左肾重、肾重/体重比、BUN、Scr、TC、TG显著降低,肾小球基底膜增厚、系膜增生等病理损害得到改善,肾脏TGF-β1、miR-192、Col1a2m RNA表达减少,SIP1m RNA及蛋白表达增高,肾脏TGF-β1、Collagen I蛋白表达降低,糖克煎剂18g/kg剂量组效果更好。结论:糖克煎剂能够治疗糖尿病肾病,其保护肾脏的机制可能与抑制miR-192信号通路相关。

Objectlve：To study the effect of Tang Ke decoction on the renal miR-192 signal pathway in diabetic nephropathy rats. Methods：The rat model of diabetic mellitus was established by streptozotocin 30 mg/kg injected into tail vein. Diabetic mellitus rats were randomly divided into model group, Tang Ke decoction prevention group（4.5g/kg） ,Tang Ke Decoction 4.5g/kg,18g/kg dose group and Fosinopfil sodium group （0. 9mg/kg）. The healthy rats were selected as the control group. Blood glucose, 24h urinary protein,left kidney weight, kidney weight/body weight ratio, blood urea nitrogen, serum creatinine, serum total cholesterol, triglyceride were determined. Hematoxylin - eosin staining was used to observe the pathological changes of renal tissues. The mRNA expressions of TGF-β1, miR-192, SIP1 and Colla2 were detected by real- time fluorescence quantitative PCR . The protein expressions of TGF-β1, SIP1 and Collagen I in kidneys were detected by Western-blot. Re- suits ： Compared with the model group, the 24h urinary protein,left kidney weight and kidney weight/body weight ratio decreased in Tang Ke decoction prevention group（4.5g/kg）, Tang Ke Decoction 4.5g/kg, 18g/kg group and Fosinopril sodium group （0.9mg/kg）. Glomenrlar basement membrane thickening, mesangial proliferation and other pathological damage improved. The mRNA expression of TGF-β1, miR-192 and Coil a2 was down-regulated. The mRNA and protein expression of SIP1 increased . The protein expression of TGF-β1 and Collagen I in kidney decreased. The effect of Tang Ke Decoction 18g/kg group was better than that of other treatment groups. Conclusion：The traditional Chinese medicine Tang Ke decoction can treat diabetic nephropathy, and its mechanism of protecting the kidney should be related to the inhi- bition of miR-192 signal pathway.