抗纤灵方对肾络病慢性肾衰竭大鼠TGF—β/Smads信号通路的影响

胡俊华　杨朔　王亚娟

[摘要] 目的 探讨抗纤灵方对肾络病慢性肾衰竭大鼠转化生长因子-β（transforming growth factor-β，TGF-β）/抗母体体节配对基因调节蛋白（Sma mothers against decapentaplegic，Smads）信号通路的影响。 方法 将48只SD大鼠分为空白组、模型组、中药组及西药组，每组各12只；其中空白组和模型组给予自由进食及饮水，而中药组和西药组则在此基础上加用抗纤灵方和氯沙坦钾灌胃；比较不同组大鼠血肌酐、24 h尿蛋白定量、Masson染色、抗母体体节配对基因调节蛋白及前体及TGF-β表达水平。 结果 与模型组相比，中药组血肌酐和24 h尿蛋白定量水平下降（P<0.05）；西药组和中药组的p-Smad2灰度比值显著低于模型组（P<0.01），西药组p-Smad2、p-Smad3及TGF-β灰度比值下降（P<0.05，P<0.01）；中药组和西药组可见肾小球肥大程度降低，毛细血管基底膜厚度、系膜基质及胶原纤维成分较模型组减少。 结论 抗纤灵方治疗慢性肾衰竭模型大鼠可有效改善肾功能，降低蛋白尿；同时对p-Smad和 TGF-β表达具有调节作用，这可能是其重要治疗机制。

[关键词] 活血化瘀；抗纤灵方；TGF-β；Smads

[中图分类号] R285.5 [文献标识码] A [文章编号] 1673-9701（2018）04-0035-04

[Abstract] Objective To investigate the effects of Kangxianling Recipe on the signaling pathway of transforming growth factor-β（TGF-β）/Sma mothers against decapentaplegic（Smads） in the rats with renal collateral diseases complicated with chronic renal failure. Methods 48 SD rats were divided into blank group， model group， TCM group and western medicine group， with 12 rats in each group； the blank group and model group were given free access to food and water， while the traditional Chinese medicine group and western medicine group were further intragastrically given Kangxianling recipe and losartan potassium on the basis of the free access to food and water； the expression levels of serum creatinine， 24h urinary protein quantification， Masson staining， Smads and precursor and TFG-β were compared between different groups. Results Compared with the model group， the levels of serum creatinine and 24 h urinary protein in the TCM group were decreased（P<0.05）； the gray-scale ratio of p-Smad2 in the western medicine group and the traditional Chinese medicine group was significantly lower than that in the model group（P<0.01）. The gray-scale ratio of p-Smad2， p-Smad3 and TGF-β in the western medicine group was decreased （P<0.05， P<0.01）. The Chinese medicine group and Western medicine group showed reduced glomerular hypertrophy， and the contents of capillary basement membrane thickness， mesangial matrix and collagen fibers were decreased compared with the model group. Conclusion Kangxianling Recipe can effectively improve renal function and reduce proteinuria in the treatment for rat models with chronic renal failure； at the same time， it also may be an important therapeutic mechanism for the regulation of p-Smad and TGF-β expression.

[Key words] Promoting circulation and removing stasis； Kangxianling Recipe； TGF-β； Smads

慢性腎衰竭是一类由多种慢性肾脏病进展至终末期引起的以肾小球滤过率下降、代谢紊乱为代表的临床症候群[1]。近年来随着慢性肾衰竭替代疗法逐步发展，患者生存率和生活质量均得到显著提高，但透析及肾移植价格过于昂贵，供体严重不足，非透析对症干预无法祛除慢性肾衰竭发病根本原因[2]。近年来中医治疗在延缓慢性肾衰竭进程进展、改善临床预后方面作用逐渐获得人们认可[3]，但具体治疗机制方面尚无明确定论。本次研究旨在通过动物实验探讨抗纤灵方对肾络病慢性肾衰竭大鼠TGF-β/Smads信号通路的影响，现报道如下。