Ac-SDKP对ROCK通路介导矽肺大鼠肌成纤维细胞分化抑制作用  

Inhibition effect of Ac-SDKP on myofibroblast differentiation regulated by ROCK pathway in rat lung with silicosis

作　　者：李淑钰[1] 徐洪[1] 孙月[1] 袁媛[1] 邓海静[1] 马文东[1] 魏中秋[2] 杨奕[3] 王瑞敏[1] 杨方[1,2] 

机构地区：[1]河北联合大学实验中心,河北唐山063000 [2]河北联合大学病理学系,063000 [3]河北联合大学教务处,063000

出　　处：《中国职业医学》2013年第2期95-99,共5页China Occupational Medicine

基　　金：国家自然科学基金资助项目(81072254);人事部留学人员科技活动项目(国人厅发[2006]164号);河北省自然基金项目(C2011401024)

摘　　要：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 inhibition effect of N-acetyl-seryl-aspartyl-lysyl-prolime （Ac-SDKP） on myofibro- blast differentiation regulated by Rho-associated coiled-coil-forming protien kinase （ROCK） pathway in rat lungs with silicosis. Methods One hundred and twenty specific pathogen free male Wistar rats were randomly divided into a control group, a silic- otic model group and an Ac-SDKP pretreatment group. SiO2 powder was douched into the bronchial tube of the rats of the silicotie model group and the Ac-SDKP pretreatment group to make the silicotic model, while the control group was douched into bronchial tube with normal saline. Each group was then subdivided into 4 sub-groups by the period of treatment （ 1, 2, 4 and 8 weeks） with 10 rats in each sub-group. Expression of a-smooth muscle action （α-SMA） was detected by immunohistochemistry. Transfor- ming growth factor beta 1 （TGF-β1）, ROCK, serum response factor （SFR）, α-SMA and type Ⅰ and type Ⅲ collagen were meas- ured by western blot. Results Compared with those of the control groups, expressions of TGF-β1, ROCK, SFR, α-SMA and type Ⅰ and type Ⅲ collagen in silicotic model groups were all increased significantly in a time-dependent manner （P 〈 0. 05 ）. Compared with those of the silicotic model groups, the expressions of TGF-β1, ROCK, SFR, α-SMA and type Ⅰand type Ⅲ collagen in the Ac-SDKP pretreatment 4 and 8 week groups were decreased obviously （ P 〈 0. 05 ）. Condttsion Ac-SDKP has a inhibition effect on myofibroblast differentiation in rat silicotic model, which involves ROCK pathway blocking mediated by TGF-β1.

关 键 词：N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸 Rho相关卷曲螺旋形成蛋白激酶 血清反应因子 α-平 滑肌肌动蛋白 矽肺 大鼠 

分 类 号：R135.2[医药卫生—劳动卫生]