PDTC对百草枯致肺损伤大鼠TGF—β1及MMP-2和TIMP-1表达的影响  

Influence of pyrrolidine dithiocarbamate （PDTC） on expression of transforming growth factor β1, matrix metalloproteinase-2 and tissue inhibitor-1 of metalloproteinase in rats with pulmonary damage induced by paraquat

作　　者：邵春风[1] 常秀丽[1] 吴强恩[1] 班婷婷[1] 姜楠[1] 姚新民[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》2008年第10期577-582,共6页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：十一五国家科技支撑计划（2006BA106B01）

摘　　要：目的探讨四氢吡咯二硫代氨基甲酸酯（pyrrolidine Dithiocarbamate，PDTC）对百草枯（paraquat，PQ）致肺损伤大鼠转化生长因子β1（TGF—β1）、基质金属蛋白酶（MMP-2）和基质金属蛋白酶组织抑制剂（TIMP-1）表达的影响。方法54只SD大鼠随机分为对照组（生理盐水组）、单纯染毒组（4个组）和干预组（4个组）。除对照组外，各组均一次性灌胃PQ40mg/kg染毒，PDTC干预组在PQ染毒后立即一次性腹腔注射PDTC120mg／kg。在染毒后3、7、14、21d各取1组动物，用反转录-聚合酶链反应（RT—PCR）法及荧光定量PCR法检测肺组织中TGF-β1、MMP-2和TIMP-1基因的表达，并观察肺组织病理改变。结果与对照组相比，染毒组大鼠血浆TGF—β1蛋白、肺组织TGF—β1、MMP-2mRNA表达随时间延长呈现先升高后降低趋势，差异有统计学意义（P〈0．05或P〈0．01），TIMP-1表达持续增高，差异有统计学意义（P〈0．01）。PDTC干预组3、14d TGF-β1 mRNA表达分别为0．54±0．08、0．72±0．04，7、14d MMP-2 mRNA表达分别为1．62±0．50、1．97±0．34，7、21d TIMP-1 mRNA表达分别为1．79±0．21、2．00±0．34，与单纯染毒组相比，均明显降低，差异有统计学意义（P〈0．05或P〈0．01）。结论PDTC对肺损伤大鼠不同时期肺组织中TGF-β1、MMP-2及TIMP-1的mRNA表达均有一定的下调作用，可能是通过减轻中毒早期炎症的损伤、调整MMPs／TIMPs间的平衡，从而延缓肺纤维化的进程。Objective To investigate the influence of pyrrolidine dithiocarbamate （PDTC） on the expres sion of transforming growth factor β1 （TGF-β1）, matrix metalloproteinase-2 （MMP-2） and tissue inhibitor-1 of metalloproteinase （TIMP-1） in rats with pulmonary damage induced by paraquat （PQ）. Methods Fifty-four healthy male SD rats were randomly assigned into the control group（ normal saline）, the PQ-treatment groups（4 groups）and the PDTC treatment groups （4 groups）. Except the rats in the control group,the rats in the PQ group were gavaged only with 40 mg/kg PQ, and PDTC group with 40 mg/kg PQ plus immediate injection 120 mg/kg PDTC（i.p）. On the 3rd, the 7th, the 14th and 28th day after treatments, one group rats of each treatments were sacrificed and lung and blood samples were collected. The level of TGF-β1 protein in the plasma, the mRNA expression of TGF-β1, MMP-2 and TIMP-1 were evaluated using RT-PCR and real-time quantitative PCR, while pathological changes of lung were examined under optical microscope and electrical microscope. Results The TGF-β1 protein,TGF-β1 and MMP-2 mRNA expression were increased significantly in the earlier stage and then decreased after PQ administration （P〈0.05 or P〈0.01 ）,while the mRNA level of TIMP-1 was augmented continuously （P〈0.01） throughout the study compared to the control group. In comparison with the PQ group, in the PDTC treatment group,the TGF-β1 mRNA expression on the 3rd and the 14th day,0.54±0.08 and 0.72±0.04 respectively, the MMP-2 mRNA expression on the 7th and 14th day, 1.62±0.50 and 1.97±0.34 respectively, and the TIMP-1 mRNA on the 7th and 21st day, 1.79±0.21 and 2.00±.34 respectively,were significantly decreased （P〈0.05 or P〈0.01 ）. Conclusion PDTC could attenuate paraquat-induced up-regnlation of TGF-β1 and its mRNA expression, MMP-2 and TIMP-1 mRNA levels, which indicates that PDTC may exert its protective effects on paraquat-induced pulmonary damage by alleviating the earlier inflammation dam

关 键 词：百草枯 呼吸窘迫综合征 四氢吡咯二硫代氨基甲酸酯 基质金属蛋白酶 

分 类 号：R686[医药卫生—骨科学]