抗纤维化短肽对矽肺大鼠肺内胶原合成与降解的调节作用  

Antifibrotic effect of N-acetyl-seryl-aspartyl-lysyl-proline mediated by the regulation of collagen synthesis and degradation in lungs of rats with silicosis

作　　者：陈萍[1] 杨方[1] 闫静波[1] 李倩[1] 张丽娟[1] 王瑞敏[1] 李丹丹[1] 武鹍飞[1] 

机构地区：[1]华北煤炭医学院实验中心

出　　处：《中国职业医学》2008年第4期274-277,共4页China Occupational Medicine

基　　金：人事部留学人员科技活动项目(国人厅发[2006]16号);河北省自然科学基金项目(C2005000807);唐山市新药基础研究重点实验室项目资助(04362001B-9)

摘　　要：目的探讨N-乙酰基-丝氨酰-天冬氨酰-赖氨酰-脯氨酸(AcSDKP)对大鼠肺内Ⅰ型和Ⅲ型胶原表达以及基质金属蛋白酶(MMP)-2和MMP-9酶活力表达的调节在拮抗矽肺纤维化形成过程中的作用。方法气管内灌注染尘法制作大鼠矽肺模型,实验动物被分为6组:矽肺模型对照1组、矽肺模型对照2组、矽肺模型1组、矽肺模型2组、抗纤维化治疗组及预防治疗组。采用HE染色对矽肺纤维化病变进行形态学观察;采用Westernblot法对肺内Ⅰ型和Ⅲ型胶原表达进行检测;采用明胶酶谱法对肺内MMP-2和MMP-9酶活力表达进行检测。结果抗纤维化治疗组Ⅰ型胶原表达量分别是矽肺模型1组与2组的71.08%和58.13%,Ⅲ型胶原表达量分别是矽肺模型1组与2组的80.13%和70.70%;预防治疗组Ⅰ型与Ⅲ型胶原表达量分别是矽肺模型2组的40.13%和65.77%。而抗纤维化治疗组MMP-2的表达分别是矽肺模型1组与2组的1.02倍;MMP-9表达分别是矽肺模型1组与2组的1.02倍和1.03倍。预防治疗组MMP-2与MMP-9表达都是矽肺模型2组的1.01倍。结论AcSDKP可以从抑制胶原合成与促进胶原降解的两个方面发挥拮抗矽肺纤维化的作用。Objective To investigate antifibrotie effect of N-aeetyl-seryl-aspartyl-lysyl-proline （AeSDKP） mediated by the regulation of type I and type Ⅲ collagen expression and MMP-2 and MMP-9 activities in lungs of rats with silicosis. Methods Silicotie models were created by trachea silicon peffusion. Rats were divided into 6 groups ： control 1 of silieotie model, control 2 of silieotie model, silieotie model 1, silicotie model 2, anti-fibrosis treatment of AeSDKP and fibrosis preventive treatment of AeSDKP. Lung fibrosis in morphology was observed with H. E staining. The expressions of type I and Ⅲ collagen and the ac-tivities of MMP-2 and MMP-9 were evaluated by western blot or zymography assay. Results Antl-fibrosis treatment of AeSDKP group compared with silieotie model 1 and silieotie model 2 group, the expression of type I collagen decreased to 71.08% and 58.13%, and expression of type Ⅲ collagen decreased to 80. 13% and 70. 70%, respectively. In fibrosis preventive treatment of AeSDKP group, the expressions of type I and type Ⅲ collagen decreased to 40. 13% and 65.77% compared to those of silieotie model 2 group. In anti-fibrosis treatment of AeSDKP group, the expression of MMP-2 was 1.02 and 1.11 times higher than those Of silicotie model 1 and silicotic model 2 group, and the expression of MMP-9 was 1.02 and 1.03 times higher than those of silieotie model 1 and silicotie model 2 group. The expressions of MMP-2 and MMP-9 of fibrosis preventive treatment of AeSDKP group was both 1.01 times higher than those of silicotie model 2 group. Conclusion AeSDKP has an effect on inhibiting lung fibrosis in rats with silicosis, which is mediated by decreasing synthesis and increasing degradation of collegen.

关 键 词：矽肺 N-乙酰基-丝氨酰-天冬氨酰-赖氨酰-脯氨酸 胶原 基质金属蛋白酶 

分 类 号：R135.2[医药卫生—劳动卫生]