中文摘要：

[目的]观察N-乙酰基-丝氨酰-天门冬氨酰-赖氨酰-脯氨酸（N-acetyl-seryl-aspartly-lysyl-proline，Ac-SDKP）能否通过对环腺苷酸活化的交换蛋白（exchange protein activated by cAMP，Epac）信号的活化，抑制矽肺大鼠及促血管生成素Ⅱ（AngⅡ）诱导的肌成纤维细胞分化。[方法]构建矽肺大鼠模型，分为对照组（4、8周组），矽肺模型组（4、8周组），Ac-SDKP抗纤维化治疗组及Ac—SDKP预防治疗组；采用AngⅡ诱导人胚肺成纤维细胞MRC-5向肌成纤维细胞分化，并予以Ac-SDKP和Epae特异性活化剂8-Me-cAMP（8-pCPT-2′-O-Me-cAMP）预处理。HE及Masson染色观察肺组织病理形态。免疫组织（细胞）化学染色法观察静平滑肌肌动蛋白（α-smooth mucle actin，α-SMA）的定位，Western blot法检测Ⅰ型胶原、α-SMA和Epac蛋白的表达。[结果]在矽肺模型组中，出现明显矽结节，结节内可见α-SMA标记的肌成纤维细胞阳性表达；Western blot法检测矽肺组织中Ⅰ型胶原、α-SMA表达上调，而Epac1表达下调；给予Ac—SDKP抗纤维化治疗或预防治疗能够抑制该变化。给予AngⅡ诱导，可见MRC-5细胞胞浆内出现明显的α-SMA阳性显色；Western blot法中可见α-SMA和Ⅰ型胶原蛋白表达上调；而予以8-Me-cAMP或Ac-SDKP预处理，能够上调Epac 1，抑制AngⅡ诱导的α-SMA和Ⅰ型胶原蛋白表达的上调。[结论]Ac-SDKP能够通过对Epac信号的活化，在体内外抑制矽肺大鼠肌成纤维细胞分化和胶原沉积，从而发挥抗矽肺纤维化的作用。

英文摘要：

[Objective] To explore the inhibition effect of N-acetyl-seryl-aspartyl-lysyl-proline（Ac-SDKP） on myofibroblast differentiation via Epac（exchange protein directly activated by c AMP） signal in silicotic rat lung fibrosis and in MRC-5 human fetal lung fibroblasts induced by angiotensin（Ang） Ⅱ. [Methods] SiO2 powders were douched in the trachea of rat to establish the silicosis model（four-week and eight-week silicosis groups） and Ac-SDKP were administered in post-（Ac-SDKP intervention group） or pre-manner（Ac-SDKP treatment group）. MRC-5 human fetal lung fibroblasts were induced to myofibroblast by Ang Ⅱ, and pre-treated with Ac-SDKP and 8-Me-c AMP（8-p CPT-2′-O-Me-c AMP）. The pathological morphologic evidence was observed by HE and Masson staining. The expression of α-smooth muscle actin（α-SMA） was located by immunohistochemistry. The protein expressions of collagen type I（Col I）, α-SMA, and Epac were measure by Western blot. [Results] Myofibroblast differentiation indicated by α-SMA positive was observed in silicosis nodules in the silicosis groups. Up-regulated expression of Col Ⅰ and α-SMA and down-regulated expression of Epac1 protein were also detected by Western blot assay. Ac-SDKP intervention or treatment showed an anti-fibrotic effect in vivoand strongly attenuated the above induced changes. The positive stain of α-SMA was observed in MRC-5 cells induced by Ang Ⅱ and accompanied with the up-regulation of Col Ⅰ and α-SMA. Pre-treatment with 8-Me-c AMP or Ac-SDKP promoted expression of Epac1 and attenuated Ang Ⅱ induced up-regulation of Col I and α-SMA. [Conclusion] Ac-SDKP could inhibit the myofibroblast differentiation and collagen deposition via Epac signal activation in silicotic rat lung fibrosis and in MRC-5 cells induced by Ang Ⅱ.