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目的:研究益气解毒活络方(YQJDHL)对早期糖尿病肾病(DN)大鼠的治疗作用及对转化生长因子-β(TGF-β)/信号转导蛋白(Smad)信号通路的影响。方法:SPF级健康雄性SD大鼠72只,尾静脉注射链脲佐菌素(STZ)制造糖尿病(DM)模型,再根据大鼠血糖值高低对各治疗组进行随机分组,分别为模型组,YQJDHL预防组(2.4 g·kg-1·d-1),YQJDHL低、高剂量治疗组(2.4,7.2 g·kg~(-1)·d~(-1)),阳性药组(盐酸贝那普利,10 mg·kg~(-1)·d~(-1)),另设正常组,每组12只,YQJDHL预防组在成DM模型后立即给予灌服YQJDHL复方;YQJDHL低、高剂量组及西药组均在成DM模型2周后即成DN模型后灌服YQJDHL复方。在灌服YQJDHL 4周末收集大鼠24 h尿液待测尿微量白蛋白,腹主动脉穿刺取血测定大鼠血糖,留取肾组织标本,苏木素-伊红(HE)染色观察肾组织病理学的变化,逆转录-聚合酶链式反应(RT-PCR)法及蛋白质免疫印迹(Western blot)法观察YQJDHL对早期DN大鼠肾组织转化生长因子-β1(TGF-β1),Smad3,Smad7 mRNA及蛋白表达的影响。结果:与正常组比较,模型组大鼠血糖及尿微量白蛋白均明显升高,TGF-β1及Smad3表达明显升高,Smad7表达明显降低(P<0.01),病理学观察显示肾组织病变较明显;YQJDHL治疗组及预防组均能降低大鼠血糖及尿微量白蛋白,降低大鼠肾组织TGF-β1及Smad3表达,升高Smad7表达(P<0.05,P<0.01),肾组织病变明显改善。结论:YQJDHL能够预防和治疗DN,其作用机制可能与TGF-β/Samd信号通路有关。
Objective: To investigate the therapeutic effect of YQJDHL on early diabetic nephropathy (DN) rats and its effect on the expression of TGF-β / Smad signaling pathway. Methods: Seventy two Sprague-Dawley (SD) male Sprague-Dawley rats were randomly divided into three groups: model group, YQJDHL prevention group (2.4 g · kg-1 · d-1), YQJDHL low and high dose treatment groups (2.4, 7.2 g · kg -1 · d -1) YQJDHL prophylaxis group was given YQJDHL compound immediately after the DM model; YQJDHL low, high dose of YQJDHL, High-dose group and western medicine group were all treated with YQJDHL compound after 2 weeks into DM model. At the end of 4 weeks, the urinary microalbuminuria of 24-hour urine samples was collected at the 4-week-end of YQJDHL and the blood glucose of abdominal aorta punctured was measured. The renal tissue samples were collected for histological examination. The expression of TGF-β1, Smad3 and Smad7 mRNA in renal tissues of early DN rats was observed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. And protein expression. Results: Compared with the normal group, the levels of blood glucose and urine microalbumin in the model group were significantly increased, the expressions of TGF-β1 and Smad3 were significantly increased, and the expression of Smad7 was significantly decreased (P <0.01). The pathological findings showed that the renal pathological changes Obviously; YQJDHL treatment group and prophylaxis group can reduce blood glucose and urinary albumin, reduce the expression of TGF-β1 and Smad3 in rat kidney, increase the expression of Smad7 (P <0.05, P <0.01) improve. Conclusion: YQJDHL can prevent and treat DN. Its mechanism may be related to TGF-β / Samd signaling pathway.