结缔组织生长因子及α平滑肌肌动蛋白在百草枯致大鼠肺纤维化中的作用  

Role of connective tissue growth factor and α-smooth muscle actin in pulmonary fibrosis among acute paraquat poisoned rats

作　　者：黄敏[1] 齐小娟[1] 张平[1] 常秀丽[1] 吴庆[1] 周志俊[1] 

机构地区：[1]复旦大学公共卫生学院教育部公共卫生安全重点实验室,上海200032

出　　处：《中华劳动卫生职业病杂志》2010年第10期729-734,共6页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：基金项目：国家科技支撑计划（2006BAI06B01）;上海市公共卫生重点学科建设项目（08GWZX0303）;上海市学科带头人培养计划（08GWD20）

摘　　要：目的 观察急性百草枯（PQ）中毒大鼠肺组织结缔组织生长因子（CTGF）及α平滑肌肌动蛋白（α-SMA）表达水平的变化,探讨PQ致肺纤维化的机制.方法 SD大鼠随机分为对照组（生理盐水）和染毒组（PQ）.染毒组给予生理盐水稀释的PQ（80 mg/kg）一次性灌胃,对照组给予生理盐水1ml/kg一次性灌胃.于不同处理后1、3、7、14、28、56 d分别以免疫组化（SABC）法检测大鼠肺组织中CTGF及α-SMA的表达强度和定位;免疫印迹（Western blot）法检测肺组织中CTGF及α-SMA蛋白的表达水平;初步分析两者表达的相关性及其表达与肺组织纤维化指标的相关性;同时观察中毒大鼠的肺组织病理变化.结果 与对照组比较,免疫组化和Western blot法检测染毒后大鼠肺组织中CTGF、α-SMA的表达变化规律较为一致,均随时间延长而逐渐升高,3、7 d时升高幅度缓慢,14～56d时增幅较大,各时段均明显高于对照组,差异有统计学意义（P＜0.05或P＜0.01）.CTGF与α-SMA、病理评分及羟脯氨酸含量均呈正相关（r=0.74,r=0.87,r=0.71,P＜0.05或P＜0.01）.病理学Masson染色可见大鼠肺组织中14～28 d时成纤维细胞大量增殖,胶原纤维数量逐渐增多.结论 在染毒大鼠肺组织中CTGF及α-SMA的表达持续增高;CTGF可能通过促使肺成纤维细胞向肌成纤维细胞转化,增加胶原分泌和基质合成,在PQ所致肺纤维化的发生发展中起重要作用.Objective To observe the expression of the cornnective tissue growth（CTGF）and αsmooth muscle actin （α-SMA） in acute paraquat （PQ）poisoned rats and investigate the mechanism of paraquat-induced pulmonary fibrosis. Methods Sprague-Dawley rats were randomly divided into two experimental groups： control group （6 rats） and PQ group （56 rats）. On the 3rd, the 7th, the 14 th, the 28 th and the 56 th day after exposure, the expression of CTGF and α-SMA were evaluated by SABC Immunohistochemistry and Western blot; and the relationship of the expression with pathologic score, hydroxyproline were also analyzed, respectively. The lung pathological changes of rats were observed and pathological evaluation was made. Results It was similar that the expression pattern of CTGF, α-SMA detected by immunohistochemistry and Western blot. With the time passing, their expression in PQ group increased gradually compared with control group（P〈0.05 or P〈0.01 ）. The increasing extent of CTGF, α-SMA were gentle on the 3 rd, the 7 th day.While their increasing extent was rapid from the 14 th to the 56 th day. CTGF was positively correlated with α-SMA, pathologic score and hydroxyproline respectively （r=0.74, r=0.87, r=0.71, P〈0.05 or P〈0.01 ）. Meanwhile, the histological changes such as lung fibroblast proliferation, disorganized collagen fibers were observed in PQ group. Conclusion CTGF and α-SMA could play an important role in the development of pulmonary fibrosis caused by paraquat poisoning; CTGF may promote the transformation of fibroblasts to myofibroblasts and further strengthen the ability of synthesis collagen and extracellular matrix.

关 键 词：百草枯 肺纤维化 结缔组织生长因子 肌动蛋白类 

分 类 号：R686[医药卫生—骨科学]