二巯丙磺钠对百草枯急性中毒大鼠肺组织基质金属蛋白酶-9 mRNA及其金属蛋白酶组织抑制剂-1 mRNA表达的影响

目的探讨二巯丙磺钠(DMPS)救治百草枯(PQ)急性中毒大鼠作用机制。方法120只雄性SD大鼠随机分为正常对照组,DMPS(200mg.kg-1,ip)对照组,PQ急性中毒(20mg.kg-1,ip)1,3,7,14和28d组以及DMPS干预(先给DMPS,15min后再给PQ)1,3,7,14和28d组。应用RT-PCR技术检测PQ急性中毒组大鼠及DMPS干预组大鼠肺组织中基质金属蛋白酶9(MMP-9)mRNA和金属蛋白酶1组织抑制剂(TIMP-1)mRNA的表达。结果PQ急性中毒组早期肺组织毛细血管扩张充血,炎症细胞浸润,后期出现较大范围慢性炎症病灶,纤维组织增生。与正常对照组比,MMP-9mRNA明显升高,分别为1.13±0.06,1.32±0.04和1.10±0.06,0.85±0.06和0.75±0.05,TIMP-1mRNA明显升高,分别为1.14±0.08,1.29±0.05,1.61±0.09,1.83±0.13和1.73±0.08;7,14和28d MMP-9mRNA/TIMP-1mRNA比值明显低于正常对照,分别为0.68±0.03,0.46±0.04和0.43±0.06;DMPS干预后,MMP-9mRNA1,3和7d和TIMP-1mRNA1,3,7,14和24d表达低于PQ中毒组,MMP-9mRNA分别为1.05±0.03,1.17±0.05和0.93±0.09;TIMP-1mRNA分别为10.0±0.07,1.15±0.09,1.09±0.06,1.16±0.08和1.23±0.09;MMP-9mRNA/TIMP-1mRNA比值略低于DMPS对照组,但高于PQ中毒组,分别为0.85±0.05,0.63±0.04和0.58±0.02(均P<0.05)。结论DMPS可能通过下调大鼠肺组织MMP-9mRNA和TIMP-1mRNA表达,上调肺组织MMP-9mRNA/TIMP-1mRNA比值发挥救治PQ中毒作用。

Effect of sodium captopropane sulfonic on expressions of matrix metalloproteinase-9 mRNA and tissue-inhibitor of metalloproteinase-1 mRNA in lungs of paraquat poisoning rats

OBJECTIVE To study the changes in matrix metalloproteinase-9 (MMP-9) mRNA, tissue-inhibitor of metalloproteinase-1 (TIMP-1) mRNA and the ratio of MMP-9 mRNA/TIMP-1 mRNA in the lungs of paraquate poisoning rats, and to investigate the protective effects of sodium dimercaptopropane sulfonate (DMPS, Unithiol). METHODS One hundred and twenty male SD rats were divided into 12 groups (n=10) randomly: normal control, DMPS control, PQ poisoning 1, 3, 7, 14 and 28 d model groups, (DMPS+PQ) 1, 3, 7, 14 and 28 d groups. PQ poisoning model was established by intraperitoneal injecting paraquate. The expression of MMP-9 mRNA and TIMP-1 mRNA in lung tissues was detected by RT-PCR. RESULTS ①By observing the changes of action and observing the lung tissues sections, the rats' PQ poisoning models was successfully established. ②The histopathology of lung showed infiltration of inflammatory cell in acute phase(within 2 weeks), the inflammation decreased gradually after 2 weeks, hyperplasia of collagen and pulmonary fibrosis were instead. Howerer, the pathological changes were alleviated obviously in the (DMPS+PQ) groups. ③Compared with the PQ groups, the expression of MMP-9 mRNA and TIMP-1 mRNA in lungs diminished greatly in the DMPS+PQ groups after rats injected DMPS(P<0.05); the ratio of MMP-9/TIMP-1 mRNA was bigger at 7, 14 and 28 d in the DMPS+PQ groups after rats injected DMPS. CONCLUSION Down-regulation of the expression of MMP-9 mRNA and TIMP-1 mRNA and up-regulation ratio of MMP-9 mRNA/TIMP-1 mRNA by DMPS may be one of mechanisms by which pulmonary injury and pulmonary fibrosis are prevented in the acute paraquate poisoning.