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目的探讨N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸(Ac-SDKP)对Rho相关卷曲螺旋形成蛋白激酶(ROCK)通路介导的肌成纤维细胞分化的抑制作用。方法无特定病原体级建康成年雄性Wistar大鼠120只随机分为对照组(支气管灌注1 ml灭菌生理氯化钠溶液)、矽肺模型组[支气管灌注质量浓度为50 g/L二氧化硅(SiO2)1 ml]、Ac-SDKP前处理组(支气管灌注质量浓度为50 g/L SiO21 ml,灌注前给予Ac-SDKP),分别于染尘后1、2、4、8周处死(每亚组10只)。采用免疫组织化学法检测肺组织内α-平滑肌肌动蛋白(α-SMA)的分布与表达,免疫印迹法检测肺组织内转化生长因子-β1(TGF-β1)、ROCK、血清反应因子(SRF)、α-SMA以及Ⅰ型和Ⅲ型胶原蛋白的表达。结果与对照组比较,矽肺模型组大鼠肺组织内TGF-β1、ROCK、SRF、α-SMA以及Ⅰ型和Ⅲ型胶原蛋白表达均增加(P<0.05),并具有一定时间依赖性。与矽肺模型组比较,Ac-SDKP前处理4、8周组,大鼠肺组织内TGF-β1、ROCK、SRF、α-SMA以及Ⅰ型和Ⅲ型胶原蛋白表达均降低(P<0.05)。结论 Ac-SDKP能够通过对TGF-β1介导的ROCK信号转导通路的调控,阻抑矽肺大鼠肌成纤维细胞的分化。
Objective To investigate the inhibitory effect of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) on the Rho-related coiled-coil-forming protein kinase (ROCK) pathway-mediated myofibroblast differentiation . Methods 120 adult male Wistar rats without grade-specific pathogen were randomly divided into control group (bronchoalveolar sterilized sodium chloride solution 1 ml), silicosis model group [bronchoalveolar lavage concentration 50 g / L silica (1ml / ml SiO2), Ac-SDKP pretreated group (21ml / ml SiO21ml, Ac-SDKP before perfusion) Group of 10). The distribution and expression of α-smooth muscle actin (α-SMA) in lung tissue were detected by immunohistochemical method. The expressions of TGF-β1, ROCK, SRF ), Α-SMA, and type I and type III collagens. Results Compared with the control group, the expression of TGF-β1, ROCK, SRF, α-SMA and type Ⅰ and type Ⅲ collagen in the lung tissue of silicosis model group were increased (P <0.05) and were time-dependent. Compared with the silicosis model group, the expression of TGF-β1, ROCK, SRF, α-SMA and type I and type III collagen in Ac-SDKP preconditioning group for 4 and 8 weeks decreased significantly (P <0.05). Conclusion Ac-SDKP can inhibit the differentiation of silicotic rat myofibroblasts through the regulation of TGF-β1-mediated ROCK signal transduction pathway.