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制。方法 采用胰酶消化法培養(yǎng)乳鼠心肌成纖維細胞，建立 AngⅡ 誘導心肌纖維化模型。實驗分為空白對照組，AngII 組，5%、10%、15% GXB含藥血清組和纈沙坦含藥血清組?？瞻讓φ战M心肌成纖維細胞以空白對照組大鼠血清溫育，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GXB對整合素 β1 mRNA 表達水平的影響；ELISA 檢測培養(yǎng)上清液中纖維連接蛋白的量；MTT 法檢測心肌成纖維細胞增殖。結(jié)果 與空白對照組比較，AngⅡ 1×10-6 mmol/L 作用心肌成纖維細胞 24 h，整合素 β1 mRNA 表達水平及纖維連接蛋白的量明顯上調(diào)（P＜0.01），心肌成纖維細胞增殖指數(shù)明顯升高（P＜0.01）；經(jīng)GXB含藥血清干預后，與AngII組比較，整合素β1 mRNA的表達水平明顯下降（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 誘導心肌纖維化，其作用機制可能與下調(diào)纖維連接蛋白/整合素β1表達有關(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．

國家自然科學基金資助項目（30600826）；上海市教育委員會基金（08cz030）