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目的 研究维甲酸 (RA)对肺纤维化大鼠肺成纤维细胞胶原表达的影响及机制。方法 正常组、纤维化组和RA治疗组 3组大鼠分别于肺纤维化模型制备后d 2 8处死 ,取肺组织进行肺成纤维细胞的原代培养。用Northernblot方法检测原代培养肺成纤维细胞前胶原α1(Ⅰ )mRNA表达 ,[3 H] 脯氨酸参入法测定胶原蛋白合成 ,凝胶迁移率法检测核因子AP 1活性 ,RT PCR方法测维甲酸受体的mRNA表达。结果 RA可诱导肺成纤维细胞RXRαmRNA的表达 ,使肺纤维化时增高的AP 1活性下调 ,并抑制前胶原α1(Ⅰ )mRNA表达及胶原蛋白合成。结论 肺纤维化时肺成纤维细胞AP 1活性增高可能是导致胶原过度表达的重要机制。RA可能通过诱导肺成纤维细胞RXRα的表达使增高的AP 1活性得以抑制 ,从而下调胶原基因的表达。
Objective To study the effect and mechanism of retinoic acid (RA) on the collagen expression of lung fibroblasts in rats with pulmonary fibrosis. Methods Three groups of rats in normal group, fibrosis group and RA treatment group were sacrificed on d 2 8 after preparation of pulmonary fibrosis model, and lung tissue was taken for primary culture of lung fibroblasts. The mRNA expression of procollagen α1 (Ⅰ) in primary cultured lung fibroblasts was detected by Northern blot. The synthesis of collagen was measured by [3 H] proline incorporation method. The activity of nuclear factor AP1 was detected by gel mobility shift assay. Retinoic acid receptor mRNA expression. Results RA induced the expression of RXRαmRNA in lung fibroblasts, down-regulated AP 1 activity in pulmonary fibrosis and inhibited the expression of procollagen α1 (Ⅰ) mRNA and collagen synthesis. Conclusions Increased AP 1 activity in lung fibroblasts may be an important mechanism leading to overexpression of collagen. RA may inhibit the increased AP 1 activity by inducing the expression of RXRα in lung fibroblasts, and thus down-regulate the expression of collagen gene.