百草枯致小鼠肺纤维化作用的实验研究

Pulmonary Fibrosis Induced by Acute Paraquat Exposure in C57BL Mice

目的探讨百草枯(PQ)对小鼠肺纤维化的作用机制。方法将8周龄健康清洁级雄性C57BL小鼠48只分为百草枯组和对照组(生理盐水),每组24只。百草枯组腹腔注射5mg/ml的百草枯(20mg/kg)连续3d。每天观察并记录各组小鼠的行为学改变。分别于染毒后第1、3、7天处死动物,取肺组织进行普通病理和免疫组化染色,统计肺组织基质金属蛋白酶(MMP-2、MMP-9)阳性细胞数。结果染毒后3d,百草枯组小鼠均出现不同程度的运动障碍、动作迟缓、震颤、竖毛和活动减少。光镜下观察,静脉瘀血、局部出血,中性粒细胞轻度增多,纤维母细胞增多,肺局部纤维组织增生;染毒后7d,出现慢性炎症、出血,局部区域可明显见纤维组织增生,间质增厚。百草枯组小鼠肺组织中MMP-2、MMP-9的表达均强于对照组,差异有统计学意义(P<0.05或P<0.01);且MMP-2、MMP-9的表达随着时间的延长而增强。结论百草枯可引起小鼠肺组织纤维化,MMP-2、MMP-9可能参与了百草枯致肺纤维化的过程。

Objective To explore the pathogenesis of pulmonary fibrosis in mice with acute paraquat （PQ） poisoning.Methods The C57BL mice aged 8 weeks,treated with paraquat （5 mg/ml） at 20 mg/kg,through intraperitoneal injection for 3 consecutive days. The changes of behavior were observed and recorded everyday and the rats were sacrificed on day 1,3,7 respectively after administration. The histopathological,immunochemical examination and count of cells with expressions of MMP-2 and MMP-9 in lung tissues were conducted. Results Compared with the control group,the mice with acute paraquat poisoning appeared dyskinesia, trembling, piloerection, less activity to a certain extent on the third day. Hemorrhage, fibroplasia and stroma thickening in part of the lung were found on 7th day. The expression of MMP-2 and MMP-9 in group of PQ poisoning was significantly upregulated （P〈0.01） compared with the control group.Conclusion MMP-2 and MMP-9 may play an important role in the pathogenesis of pulmonary fibrosis induced by paraquat in C57BL mice.