PDTC对百草枯致肺纤维化大鼠结缔组织生长因子及Ⅰ、Ⅲ型胶原的影响  

Intervention of pyrrolidine dithiocarbamate on expressions of connective tiss growth factor,type Ⅰ collagen, and type Ⅲ collage in acute paraquat poisoned rats

作　　者：黄敏[1] 杨惠芳[1] 张平[2] 常秀丽[2] 周志俊[2] 

机构地区：[1]宁夏医科大学公共卫生学院劳动卫生与职业病教研室,银川750004 [2]复旦大学公共卫生学院/教育部公共卫生安全重点实验室

出　　处：《中华劳动卫生职业病杂志》2013年第1期4-9,共6页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：宁夏高等学校科学研究项目（[20111263）;宁夏回族自治区卫生厅重点科研计划课题（2102005）;宁夏医科大学特殊人才启动项目（XT2011001）

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）、Ⅰ型胶原（ColⅠ）、Ⅲ型胶原（ColⅢ）的动态变化及四氢吡咯二硫代氨基甲酸酯（PDTC）的干预效果，探讨PQ致肺纤维化机制及PDTC干预作用。方法sD大鼠随机分为对照组（6只）、PQ染毒组（56只）、PDTC干预组（46只）。染毒组和干预组给予PO（80mg／kg）一次性灌胃后2h，染毒组给予等量生理盐水腹腔注射，PDTC干预组给予PDTC（100mg／kg）一次性腹腔注射；对照组给予生理盐水1ml／kg灌胃后2h，给予等量生理盐水腹腔注射。于不同处理后1、3、7、14、25、56d蛋白免疫印迹法（Westernblot）测定大鼠肺组织CTGF蛋白表达；实时荧光定量多聚酶链式反应（real-timePCR）测定CTGF、ColⅠ、ColⅢ mRNA表达水平；同时测定肺组织羟脯氨酸（hyp）含量，观察中毒大鼠的肺组织病理变化。结果染毒组大鼠肺组织CTGF蛋白表达随时间延长而逐渐升高，3～14d升高幅度缓慢，28～56d增幅较大，各时点均明显高于对照组，差异有统计学意义（P〈0．05或P〈0．01）。染毒组大鼠肺组织CTGFmRNA表达水平于染毒后1d即明显升高，3～14d表达迅速升高，28～56d维持在较高水平，各时点均明显高于对照组，差异有统计学意义（P〈0．01）。染毒组染毒后1、3dColⅠmRNA表达无明显变化，7d表达略微增强，14～56d水平大幅度升高，与对照组比较，7～56dmRNA水平明显升高，差异有统计学意义（P〈0．05或P〈0．01）；染毒组ColⅢmRNA水平于染毒后1d即开始升高，7d达到高峰，之后呈下降趋势，各时点均明显高于对照组，差异有统计学意义（P〈0．05或P〈0．01）；Masson染色可见染毒后14～28d成纤维细胞大量增殖，胶原纤维数量逐渐增多。与染毒组比较，PDTC干预组大鼠肺组织CTGF蛋白表达降低、CTGF、ColⅠ、ColⅢmRNA表达下调，相应时点的差异Objective To observe the changes in the expression of connective tissue growth factor （CTGF）, type Ⅰ collagen （Col Ⅰ ）, and type Ⅲ collagen （Col Ⅲ ） among the rats with acute paraquat （PQ） poisoning and the intervention effect of pyrrolidine dithiocarbamate （PDTC） on their expression, and to investigate the mechanism of PQ-induced pulmonary fibrosis and the intervention effect of PDTC on the disease. Methods Sprague-Dawley rats were randomly divided into control group （n=6）, PQ group （n=36）, and PQ＋ PDTC group （n=36）. The PQ group and PQ＋PDTC group were given a single dose of saline-diluted PQ （80 mg/ kg） by gavage; 2 h later, the PQ＋PDTC group was intraperitoneally injected with a single dose of PDTC （100 mg/kg）, and the PQ group was intraperitoneally injected with the same amount of saline. The control group was given saline （ 1 ml/kg） by gavage and was intraperitoneally injected with the same amount of saline 2 h later. At 1, 3, 7, 14, 25, and 56 days after operation, the protein expression of CTGF was evaluated by Western blot; the mRNA expression of CTGF, Col Ⅰ , and Col Ⅲ was analyzed by real-time quantitative PCR; the content ofhydroxyproline in lung tissue was measured, and the pathological changes of lung tissue of the poisoned rats were observed. Results The protein expression of CTGF in the PQ group increased as the time went on, slowly from the 3rd to the 14th day and rapidly from the 28th to the 56th day, significantly higher than that in the control group at each time point （P〈0.05 or P〈0.01）. The mRNA expression of CTGF in the PQ group began to rise markedly on the 1st day, increased rapidly from the 3rd to the 14th day, and remained at a relatively high level from the 28th to the 56th day, significantly higher than that in the control group at each time point （P〈0.01）. The mRNA expression of Col Ⅰ in the PQ group changed little on the 1st and 3rd day, increased slightly on the 7th day, and increased greatly from the 14th

关 键 词：百草枯 急性肺损伤 肺纤维化 结缔组织生长因子 胶原 

分 类 号：R285.5[医药卫生—中药学]