抗纤维化短肽对大鼠矽肺纤维化MCP-1、ED-1表达的影响

目的探讨抗纤维化短肽N-乙酰基-丝氨酰-天冬氨酰-赖氨酰-脯氨酸(AcSDKP)对大鼠肺内单核细胞趋化蛋白-1(MCP-1)、ED-1表达的影响在拮抗矽肺纤维化形成过程中的作用。方法气管内灌尘法制作大鼠矽肺纤维化动物模型,实验大鼠随机分为6组,包括:对照1组,对照2组和矽肺模型1组,矽肺模型2组,矽肺抗纤维化治疗组,矽肺预防治疗组。采用HE染色对矽肺纤维化病变及其变化特点进行形态学观察;采用羟脯氨酸法对矽肺大鼠肺内胶原含量进行检测;采用免疫组织化学方法检测各组大鼠肺组织中MCP-1的表达与巨噬细胞(ED-1阳性)的数量。结果抗纤维化治疗组与矽肺模型1组与2组相比,矽结节面积下降到84.28%和67.93%,羟脯氨酸含量下降到70.89%和58.18%,MCP-1蛋白表达下降到82.3%和84.1%,MCP-1阳性细胞数下降到67.4%和72.5%,ED-1蛋白表达下降到78.7%和79.3%,ED-1阳性细胞数下降到54.4%和66.8%;预防治疗组与矽肺模型2组相比,矽结节面积下降到61.13%,羟脯氨酸含量下降到60.27%,MCP-1蛋白表达和阳性细胞数分别下降到85.2%和86.3%,ED-1蛋白表达和阳性细胞数分别下降到87.2%和74.9%。结论AcSDKP具有拮抗矽肺纤维化的作用,这可能与其抑制巨噬细胞在肺内的浸润、聚集,减轻了尘性肺泡炎的程度相关。

Antifibrotic effects of N-acetyl-seryl-aspartyl-lysyl-proline mediated by the regulation of MCP-1 and ED-1 expression on rats with silicosis

Objective To investigate whether the effect of N-acetyl-seryl-aspartyl-lysyl-proline(AcSDKP) on macrophage infiltration was involved in AcSDKP 's antifibrotic effect on the rats with silicosis.Methods Rats were intratracheally instilled with silica as silicotic models in the experiment.Wistar rats were divided into 6 groups randomly: control 1,control 2,silicotic model 1,silicotic model 2,anti-fibrosis treatment of AcSDKP,Preventing fibrosis treatment of AcSDKP.Lung fibrosis in morphology was observed by H.E staining.Collage content was detected by Hydroxyproline assy.The expressions of MCP-1 and ED-1 in lung were observed by immunohistochemistry.Results In anti-fibrosis treatment of AcSDKP group,area of of silicosis nodules decreased to 84.28% and 67.93%,content of hydroxyproline decreased to 70.89% and 58.18%,protein expression of MCP-1 decreased to 82.3% and 84.1%,cell numbers of MCP-1 decreased to 67.4% and 72.5%,protein expression of ED-1 decreased to 78.7% and 79.3%,cell numbers of ED-1 decreased to 54.4% and 66.8%.In Preventing fibrosis treatment of AcSDKP group,area of silicosis nodules decreased to 61.13%,content of hydroxyproline decreased to 60.27%,protein expression and cell numbers of MCP-1 decreased to 85.2% and 86.3%,protein expression and cell numbers of ED-1 decreased to 87.2% and 74.9%.Conclusion AcSDKP can decrease and reverse pulmonary fibrosis in rats with silicosis which may be mediated in part by inhibition of the infiltration and aggregation of macrophage and the severity of silicotic alveolitis.