抗纖靈方對腎絡病慢性腎衰竭大鼠TGF—β/Smads信號通路的影響

胡俊華　楊朔　王亞娟

[摘要] 目的 探討抗纖靈方對腎絡病慢性腎衰竭大鼠轉化生長因子-β（transforming growth factor-β，TGF-β）/抗母體體節配對基因調節蛋白（Sma mothers against decapentaplegic，Smads）信號通路的影響。 方法 將48只SD大鼠分為空白組、模型組、中藥組及西藥組，每組各12只；其中空白組和模型組給予自由進食及飲水，而中藥組和西藥組則在此基礎上加用抗纖靈方和氯沙坦鉀灌胃；比較不同組大鼠血肌酐、24 h尿蛋白定量、Masson染色、抗母體體節配對基因調節蛋白及前體及TGF-β表達水平。 結果 與模型組相比，中藥組血肌酐和24 h尿蛋白定量水平下降（P<0.05）；西藥組和中藥組的p-Smad2灰度比值顯著低于模型組（P<0.01），西藥組p-Smad2、p-Smad3及TGF-β灰度比值下降（P<0.05，P<0.01）；中藥組和西藥組可見腎小球肥大程度降低，毛細血管基底膜厚度、系膜基質及膠原纖維成分較模型組減少。 結論 抗纖靈方治療慢性腎衰竭模型大鼠可有效改善腎功能，降低蛋白尿；同時對p-Smad和 TGF-β表達具有調節作用，這可能是其重要治療機制。

[關鍵詞] 活血化瘀；抗纖靈方；TGF-β；Smads

[中圖分類號] R285.5 [文獻標識碼] A [文章編號] 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

慢性腎衰竭是一類由多種慢性腎臟病進展至終末期引起的以腎小球濾過率下降、代謝紊亂為代表的臨床癥候群[1]。近年來隨著慢性腎衰竭替代療法逐步發展，患者生存率和生活質量均得到顯著提高，但透析及腎移植價格過于昂貴，供體嚴重不足，非透析對癥干預無法祛除慢性腎衰竭發病根本原因[2]。近年來中醫治療在延緩慢性腎衰竭進程進展、改善臨床預后方面作用逐漸獲得人們認可[3]，但具體治療機制方面尚無明確定論。本次研究旨在通過動物實驗探討抗纖靈方對腎絡病慢性腎衰竭大鼠TGF-β/Smads信號通路的影響，現報道如下。