益氣通陽(yáng)方對(duì)單側(cè)輸尿管梗阻大鼠腎間質(zhì)纖維化的影響

韓成鵬　馬華　李榮榮　李軍娜

摘要：目的 觀察益氣通陽(yáng)方對(duì)單側(cè)輸尿管梗阻（UUO）大鼠腎間質(zhì)纖維化及TGF-β1/Smad7信號(hào)通路的影響，探討其可能的作用機(jī)制。方法 將40只SD大鼠隨機(jī)分為假手術(shù)組、模型組、中藥組和西藥組各10只。除假手術(shù)組外，其余各組建立UUO模型。西藥組予依那普利溶液0.18 mg/mL灌胃，中藥組予益氣通陽(yáng)方濃縮液1.188 g/mL灌胃，假手術(shù)組和模型組予等量生理鹽水灌胃，每日1次。14 d后心臟取血檢測(cè)大鼠血清肌酐（SCr）和尿素氮（BUN）水平，處死大鼠取其腎組織行HE和Masson染色，免疫組化檢測(cè)腎組織轉(zhuǎn)化生長(zhǎng)因子-β1（TGF-β1）和纖維連接蛋白（FN）的表達(dá)，Western blot和RT-PCR分別檢測(cè)Smad7蛋白和mRNA的表達(dá)。結(jié)果 與假手術(shù)組比較，模型組大鼠血清SCr、BUN明顯升高（P<0.01），病理改變明顯，TGF-β1、FN蛋白表達(dá)明顯升高（P<0.01），Smad7 蛋白和mRNA表達(dá)明顯降低（P<0.01）；與模型組比較，中藥組和西藥組大鼠血清SCr、BUN明顯降低（P<0.05），病理改變減輕，TGF-β1、FN蛋白表達(dá)明顯降低（P<0.05），Smad7蛋白和mRNA表達(dá)明顯升高（P<0.05）。結(jié)論 益氣通陽(yáng)方可能通過(guò)上調(diào)Smad7表達(dá)，抑制UUO大鼠腎組織TGF-β1的高表達(dá)，進(jìn)而延緩腎間質(zhì)纖維化進(jìn)展。

關(guān)鍵詞：腎間質(zhì)纖維化；益氣通陽(yáng)方；轉(zhuǎn)化生長(zhǎng)因子-β1；Smad7信號(hào)蛋白；大鼠

中圖分類號(hào)：R285.5 文獻(xiàn)標(biāo)識(shí)碼：A 文章編號(hào)：1005-5304（2019）03-0060-05

Abstract： Objective To investigate the effects of Yiqi Tongyang Decoction on renal interstitial fibrosis in unilateral ureteral obstruction （UUO） rats and the role of TGF-β1/Smad7 signaling pathway； To explore possible the mechanism of action. Methods Totally 40 SD rats were randomly divided into sham-operation group， model group， TCM group and Western medicine group， with 10 rats in each group. Excluding the sham-operation group， UUO models were established in the others. Then the Western medicine group was given enalapril liquid 0.18 mg/mL for gavage； the TCM group was given Yiqi Tongyang Decoction concentrated liquid 1.188 g/mL for gavage； the other groups were given the same amount of normal saline for gavage once a day. After 14 days， serum was collected for detecting the levels of SCr and BUN. Then the rats were killed for taking the renal tissue and conducting HE and Masson staining. The expressions of TGF-β1 and FN protein were detected by using immunohistochemistry method. Western blot and RT-PCR were used to detect the expressions of Smad7 protein and mRNA. Results Compared with the sham-operation group， the levels of SCr and BUN in the model group significantly increased （P<0.01）， and the pathological changes were obvious， the expression of TGF-β1 and FN were significantly increased （P<0.01）， and the expression of Smad7 and its mRNA decreased （P<0.01）. Compared with the model group， the levels of SCr and BUN in the TCM group and Western medicine group significantly decreased （P<0.05）， the degree of tubulointerstitial injury decreased， also the expressions of TGF-β1 and FN protein significantly decreased （P<0.05）， while Smad7 and its mRNA expression significantly increased （P<0.05）. Conclusion Yiqi Tongyang Decoction can reduce renal interstitial fibrosis possibly by inhibiting the expression of TGF-β1 and up-regulating the expression of Smad7 in UUO rats.