急性百草枯中毒大鼠肺组织中基质金属蛋白酶及其组织抑制剂表达变化的研究

目的观察急性百草枯中毒大鼠肺组织中基质金属蛋白酶（MMP-2、MMP-9）及其组织抑制因子1（TIMP-1）的表达变化，探讨其在百草枯（PQ）所致肺损伤中的作用。方法80只SD大鼠，随机分为染毒组和对照组。对照组用生理盐水灌胃；染毒组用PQ按50mg/kg灌胃染毒；分别于灌药后1、3、7、14、21、28、35d观察两组肺组织病理变化，同时采用RT—PCR检测肺组织MMP-2mRNA、MMP-9mRNA及TIMP-1mRNA的表达。结果与对照组相比，染毒组大鼠肺组织中MMP-2 mRNA的表达从1d就明显增强，7d达高峰，此后开始缓慢下降，14d至28d仍高于对照组，35d与对照组相比无统计学差异；MMP-9mRNA的表达1d至7d高于对照组，14d降至对照组水平；而TIMP-mRNA的表达从1d开始增强，14d迭高峰，以后维持在高水平，至35d仍明显高于对照组。结论MMP-2、MMP-9及TIMP—1在PQ中毒大鼠肺损伤中起重要的调节作用，大鼠肺纤维化与MMPs／TIMP比例的失衡有关。

Study on the expression of matrix metalloproteinases and its tissue inhibitor in lung tissue of rats with acute paraquat poisoning

Objective To investigate the expression and effect of matrix metallopreteinases and its tissue inhibitor in lung injury of rats with acute paraquat poisoning. Methods 80 SD rats were randomly divided into control group and poisoned group. Atl, 3, 7, 14, 21, 28 and 35 days after exposure, ten rats of each group were used to assess lung pathological changes and the expression of MMP- 2 mRNA, MMP - 9 mRNA and TIMP - ImRNA in lungs were evaluated by RT - PCR. Results Compared with control group, the expression of MMP - 2 mRNA in lung tissue of poisoned group markedly increased at the first day, reached the peak at the 7th day, decreased slowly afterwards, and retumed to nomral level at the 3501 day. Expression of MMP - 9mRNA rose from 1 to 7 day,returned to baseline at the 14th day. Expression of TIMP- 1 mRNA markedly inereased at the first day, reached the peak at the 14th day, and kept at relatively high levels up to the 35th day. Conclusion MMP - 2, MMP- 9 and TIMP 1 play an important role in lung injury of rats with acute paraquat poisoning. The development of pulmonary fibrosis is closely related to the imbalance of MMPs/TIMP.