温阳活血方对慢性马兜铃酸肾病大鼠肾组织Caspase-3和BMP-7表达的影响

Effect of Wen Yang Huo Xue Fang on the Expression of Caspase-3 and BMP-7 in Rats of Chronic Aristolochic Acid Nephropathy

目的:观察温阳活血方对慢性马兜铃酸肾病大鼠肾组织Caspase-3和BMP-7表达的影响,探讨温阳活血方对慢性马兜铃酸肾病的肾保护机制。方法:将48只雄性SD大鼠随机分为5组:(1)正常对照组(n=8):予生理盐水灌胃;(2)模型组(n=10):按关木通水煎液10mL.kg-1.d-1(相当于关木通40g.kg-1.d-1,马兜铃酸A 2.6mg.kg-1.d-1)给大鼠灌胃;(3)中药组(n=10):在模型组基础上,再予温阳活血方30g.kg-1.d-1灌胃;(4)西药组(n=10):在模型组基础上,再予科素亚33.3mg.kg-1.d-1灌胃;(5)中西药结合组(n=10):在模型组基础上,再予(温阳活血方30g.kg-1.d-1+科素亚33.3mg.kg-1.d-1)灌胃。20周末,检测大鼠尿蛋白、肾功能,光镜和电镜观察肾脏病理,采用免疫组化检测肾组织Caspase-3和BMP-7的表达。结果:与正常组和治疗组比较,模型组大鼠24h尿蛋白、Scr、BUN均明显升高(P<0.01);肾脏病理显示治疗组较模型组肾损害明显减轻;与正常对照组和治疗组比较,模型组大鼠肾组织Caspase-3表达明显升高(P<0.05),BMP-7的表达减少(P<0.01)。结论:温阳活血方能有效防治慢性马兜铃酸肾病,其机制可能与降低Caspase-3升高BMP-7有关。

Objective：To explore the protective mechanism of Wen Yang Huo Xue Fang（WYI-IXF） on kidneys by investigating the effect of WYHXF on the expression of Caspase - 3 and BMP - 7 in rats with chronic aristolochic acid nephropathy. Methods ： Fourty -eight male SD rats were randomly divided into five groups. Group A （n = 8 ）were treated with normal saline（ 10mL · kg^-1 · d^-1）. Group B（n = 10）were treated with caulis Aristolochia Manshurlensis decoction（ Aristolochia Manshuriensis 40g · kg^-1 · d^-1, Aristolochic acid A2. 6mg · kg^-1 · d^-1 ）. Group C （ n = 10） were treated with WYHXF （ 30g · kg^-1· d ^-1 ） after the mice being modeled with the above-mentioned method. Group D（ n = 10）were treated with Losartan Potassium Tablets（33.3mg · kg^-1 · d ^-1 ） after the mice being modeled with the above-mentioned method. Group E（ n = 10） were treated with WYHXF（ 30g · kg^-1 · d^-1）and Losartan Potassium Tablets（33.3mg · kg^-1 · d^-1） after the mice being modeled with the above-mentioned method. After 20 weeks, detection of rat urine protein, renal function, observation of renal pathology, detection of renal tissue Caspase - 3 and BMP - 7 by Immunohistochemistry. Results ： Compared with those in the normal control group and the therapy group, the level of 24-hour urine protein,Scr,BUN were significantly increased in the model group（ P 〈 0. 01 ） ;Renal pathology showed that the treatment group compared to the model group significantly reduce renal damage;Compared with those in the normal control group and the therapy group,the expression of Caspase- 3 was significantly increased（ P 〈 0. 05）, while BMP- 7 was significantly decreased in the model group （P 〈 0. 01 ）. Conclusion：WYHXF exerted protective effect on CAAN probably via reduction of Caspase - 3 and elevation of BMP - 7.