摘 要：目的 研究整合素 β1 和纖維連接蛋白在血管緊張素Ⅱ（AngⅡ）誘導(dǎo)心肌纖維化中的作用，探討瓜蔞薤白半夏湯(GXB)抗心肌纖維化的作用機(jī)制。方法 采用胰酶消化法培養(yǎng)乳鼠心肌成纖維細(xì)胞，建立 AngⅡ 誘導(dǎo)心肌纖維化模型。實(shí)驗(yàn)分為空白對(duì)照組，AngII 組，5%、10%、15% GXB含藥血清組和纈沙坦含藥血清組?？瞻讓?duì)照組心肌成纖維細(xì)胞以空白對(duì)照組大鼠血清溫育，其余各組均以 AngⅡ 1×10-6 mmol/L 刺激 24 h 后，再分別以空白對(duì)照組大鼠血清、5% GXB含藥血清、10% GXB含藥血清、15% GXB含藥血清、纈沙坦含藥血清溫育 24 h。RT-PCR 法檢測(cè)GXB對(duì)整合素 β1 mRNA 表達(dá)水平的影響；ELISA 檢測(cè)培養(yǎng)上清液中纖維連接蛋白的量；MTT 法檢測(cè)心肌成纖維細(xì)胞增殖。結(jié)果 與空白對(duì)照組比較，AngⅡ 1×10-6 mmol/L 作用心肌成纖維細(xì)胞 24 h，整合素 β1 mRNA 表達(dá)水平及纖維連接蛋白的量明顯上調(diào)（P＜0.01），心肌成纖維細(xì)胞增殖指數(shù)明顯升高（P＜0.01）；經(jīng)GXB含藥血清干預(yù)后，與AngII組比較，整合素β1 mRNA的表達(dá)水平明顯下降（P＜0.01），纖維連接蛋白的量減少（P＜0.05），心肌成纖維細(xì)胞增殖指數(shù)明顯降低（P＜0.01）。結(jié)論 瓜蔞薤白半夏湯能夠抑制 AngⅡ 誘導(dǎo)心肌纖維化，其作用機(jī)制可能與下調(diào)纖維連接蛋白/整合素β1表達(dá)有關(guān)。

Abstract: Objective To investigate the effects of integrin β1 and fibronectin on cardiac fibroblasts induced by Angiotensin Ⅱ（AngⅡ），and to expore the mechanism of Gualou Xiebai Banxia Decoction（GXB），a compound traditional Chinese herbal medicine，in reversing myocardial fibrosis．Methods Fibroblasts derived from neonatal rats were cultured with enzymatic dissociation，and myocardial fibrosis was induced by AngⅡ．The fibroblasts were divided into normal control group，AngⅡ group，5% GXB-containing group，10% GXB-containing group，15% GXB-containing group，and Valsartan-containing group．Fibroblasts in normal control group were incubated by normal serum．In other experimental groups，fibroblasts were induced for 24 hours by AngⅡ（1×10-6 mmol/L），then incubated by 5% GXB-containing serum，10% GXB-containing serum，15% GXB- containing serum，and Valsartan-containing serum for 24 hours respectively．Integrin β1 mRNA expression was detected by RT-PCR，fibronectin content in the extracellular matrix were measured by ELISA，and proliferation of cardiac fibroblasts was measured by MTT．Results After 24-hour stimulation of Ang Ⅱ in fibroblasts，compared with those in normal control group，the expression of integrin β1 mRNA raised significantly（P<0.01），fibronectin increased significantly（P<0.05）．The model of myocardial fibrosis was intervented by different dosages of Gualou Xiebai Decoction．Compared with AngⅡ group，the integrin β1 mRNA expression showed a significant downward trend（P＜0.01）and fibronectin decreased（P＜0.05）．Conclusion Gualou Xiebai Decoction can inhibit cardiac fibroblast induced by AngiotensinⅡ，and the mechanism may be related to fibronectin/integrin β1．

國(guó)家自然科學(xué)基金資助項(xiàng)目（30600826）；上海市教育委員會(huì)基金（08cz030）