TGF-β/Smads信号通路在川陈皮素治疗糖尿病肾病大鼠中的变化特点研究

Study on the changes of TGF-β/Smads signaling pathway in the treatment of diabetic nephropathy rats with nobiletin

目的观察川陈皮素对糖尿病肾病大鼠治疗作用及对TGF-β/Smads信号通路的影响。方法 120只SD大鼠随机分为正常组、模型组、川陈皮素低、中、高剂量组以及贝那普利组,各20只,高脂高糖饮食1月+STZ腹腔注射建立糖尿病肾病模型,治疗6周后处死,观察肾脏病理学、检测24 h尿量、尿蛋白定量、BUN和Scr,同时检测TGF-β、Smad2和Smad7蛋白及mRNA表达特点。结果 HE染色,正常组肾小球、肾小管以及肾间质清晰,模型组有明显肾小球萎缩和硬化性改变,与模型组比较,各治疗组明显改善;与正常组比较,模型组24尿量、尿蛋白定量、BUN和Scr均明显升高(P<0.05),与模型组比较,各治疗组明显降低(P<0.05);与正常组比较,模型组TGF-β和Smad2蛋白和mRNA表达升高(P<0.05),Smad7降低(P<0.05),与模型组比较,各治疗组TGF-β和Smad2降低(P<0.05),Smad7升高(P<0.05)。结论川陈皮素能减少尿蛋白、降低BUN和Scr,降低肾脏TGF-β和Smad2表达,促进Smad7表达,进而保护糖尿病肾病肾脏损害。

Objective To observe the therapeutic effect of nobiletin to diabetic nephropathy rats,and research the effect of nobiletin to TGF-β/Smads signaling pathway.Methods A total of 120 SD rats were randomly divided into normal,model,low,medium,high doses of nobiletin,and benazepril group (n=20),the rat model of diabetic nephropathy was established by the high-dose fat diets one months and STZ injection.After 6 weeks of drug treatment,the histopathology of the kidney was observed,the urine volume,24 h urine protein,BUN and Scr were measured,after the expression of TGF-β,Smad2 and Smad7 proteins and mRNA were also detected.Results HE staining showed it has the clear glomeruli,renal tubules and interstitial space in the normal group,the slices showed obvious glomerular atrophy and sclerosing in the model group.Compared with the model group,the slices in the treatment group were significantly improved.Compared with the normal group,the 24 urine volume,24 h urine protein quantitation,BUN and Scr were increased in the model group (P<0.05);compared with the model group,those indexes in the treatment groups were lower (P<0.05).The expression of TGF-β and Smad2 protein and mRNA in the model group compared with them in the normal group were increased (P<0.05),Smad7 was significantly decreased (P<0.05);compared with the model group,they were lower them in the low,medium and high dose nobiletin and benazepril groups (P<0.05),Smad7 was significantly increased (P<0.05).Conclusion The nobiletin can reduce urine protein,decrease the BUN and Scr,reduce the expression of TGF-β and Smad2 in kidney,promote the expression of Smad7,and finally protect STZ-induced kidney injury of rats.