吡非尼酮对百草枯诱导的大鼠急性肺损伤保护作用研究

摘要

Objective: To study the protective effect of Pirfenidone (PF) against Paraquat (PQ)-induced lung damage in rats and its underlying mechanisms. Methods: Thirty rats were randomly divided into five groups: control group, PQ group, PF low-, middle- and high-dose treatment groups. The activties of super-oxide dismutase (SOD), the contents of malondialdehyde (MDA), IL-6 and TNF-α in the lung tissues were examined. Also, the expression of TGF-β, CTGF and smad3 in lung tissues w measured by Western-blot-ting. The lung coefficient was calculated and pathological changes of lung tissues were observed by HE staining. Results: Compared with the control group rats, the levels of oxidative stress and inflammation were increased in the lung tissues of PQ group rats, while the PF group rats exhibited significant decrease in oxidative stress and inflammation. The expression of TGF-β, CTGF and smad3 were increased in PQ group rats. The sections showed that the lung tissue damage was obvious in PQ group rats with alveolar a-trophy, overinflation, inflammatory cell infiltration and pulmonary fibrosis. However, the administration of PF significantly decreased the damage. Conclusion: The results indicated that PF had a protective effect a-gainst PQ-induced lung damage in rats. It is considered that this protective effect may be related to its free radical scavenging activity, inhibition of inflammation and inhibition of the expression of TGF-β, CTGF and smad3.%目的：研究吡非尼酮（pirfenidone，PF）对百草枯（paraquat，PQ）诱导的大鼠急性肺损伤的保护作用及机制。方法：30只雄性成年SD大鼠随机分为对照组、PQ组、PF治疗低、中、高组，采用腹腔注射20% PQ溶液诱导大鼠成急性PQ中毒模型。测定各组大鼠肺组织中超氧化物歧化酶（SOD）活性、丙二醛（MDA）以及炎症因子白介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）含量变化，同时以蛋白免疫印迹法测定转化生长因子（TGF-β）、结缔组织生长因子（CTGF）、smad3蛋白表达。HE染色观察大鼠肺组织病理改变。结果：与对照组大鼠相比，PQ组大鼠肺组织氧化应激和炎症反应水平明显升高，而给予PF可明显抑制中毒大鼠肺组织氧化应激和炎症反应。蛋白免疫印迹结果显示，中毒大鼠肺组织中TGF-β、CTGF、smad3蛋白表达显著升高，光镜观察显示中毒大鼠肺组织大量肺泡萎缩，部分过度膨胀，组织炎性浸润和纤维化明显。给予PF治疗后，大鼠肺组织TGF-β、CTGF和smad3蛋白表达以及组织损伤和纤维化显著降低。结论：PF可以减轻百草枯中毒大鼠肺组织损伤，其治疗作用可能与其抗炎、抗氧化、抑制TGF-β、CTGF和smad3表达有关。