硫酸镁对百草枯中毒肺损伤后大鼠环氧化酶-2和钙-ATP酶表达及胶原生成的实验研究

The expression of COX-2, Ca^2＋ -ATPase and collagenation in paraquat- induced lung injury rats treated with magnesium sulfate

目的观察硫酸镁治疗大鼠百草枯（PQ）中毒时肺组织中环氧化酶-2（COX-2）和钙-ATP酶（Ca^2＋-ATPase）的表达及胶原生成变化。方法将60只雄性SD大鼠，按随机数字法分为中毒组（PQ组）、干预组（MS组）和对照组（NS组）。PQ组及MS组一次性胃管内注入百草枯80mg／kg制备百草枯中毒模型；MS组每天腹腔注入硫酸镁30ms／kg；NS组给予等量生理盐水。按造模后时间分为第3天、7天、14天和21天四个亚组（n=5）。采用免疫组化检测肺组织内COX-2和胶原纤维的表达，并检测肺组织匀浆Ca^2＋TPase含量。结果随中毒时间延长，PQ组和MS组COX-2进行性增强，与NS组比较差异有统计学意义（P〈0．05）。MS组COX-2比PQ组明显减弱（P〈0．05）。PQ组较MS组Ca^2＋ATPase减少（P〈0．05）。在各时间点NS组与PQ组比较差异有统计学意义（P〈0．01），Ns组与MS组在第3天、第7天、第14天比较差异有统计学意义（P〈0．05）。MS组Ca^2＋ATPase在第14天开始升高，到第21天恢复正常。而PQ组在第21天Ca^2＋ATPase开始出现升高。胶原染色在第3天差异不明显，PQ组在第14天起胶原纤维逐渐增加，到第21天肺组织内大量的胶原纤维充满肺野，出现显著的纤维化表现。与同时间点的PQ组比较，MS组胶原纤维增生少，肺组织结构破坏轻。结论硫酸镁可能通过抑制COX-2、抑制钙超负荷和减少胶原生成途径发挥对百草枯中毒肺损伤大鼠的干预治疗作用。

Objective To investigate the expressions of COX - 2, Ca^2＋ - ATPase and collagenation in paraquat -induced lung injury in rats treated with magnesium sulfate. Methods Sixty male Sprague - Dawley rats were randomly （ random number method） divided into three different groups ： paraquat intoxication group （PQ group） ; magnesium sulfate group （MS group） ; controlled group （NS group）. PQ group and MS group were given paraquat through intra -gastric administration （80 mg/kg）. MS group was intraperitoneally administrated given douched magnesium sulfate （30 mg/kg per day）, while NS group was given equivalent volume of normal saline. The rats of these three groups were further divided into four sub- groups： 3 d, 7 d, 14 d and 21 d. The level activity of Ca^2＋- ATPase in lung homogenate was measured. The expressions of COX -2 and collagen fiber were detected by immunohistochemistry. Results The COX -2 expression was significantly higher in the rats lung of paraquat intoxication groups （PQ group and MS group） compared with NS group, while there was a significant difference between MS group and PQ group （P 〈 0.05 ）. The Ca^2＋ - ATPase activity in PQ group was lower than that of MS group（ P 〈 0. 05 ）. Compared with NS group, the Ca^2 ＋ - ATPase activity of PQ group was significantly different during treatment period （ P 〈 0. 01 ）, but the Ca^2＋- ATPase activity of MS group was significantly different on the 3rd, 7th and 2hh day （P 〈0.05）. In MS group, the Ca^2＋-ATPase activity increased from the 14th day and returned to normal level on the 21th day. However, the Ca^2＋- ATPase activity of PQ group did not increase until on the 21th day. The collagen fiber among these groups had no significant difference on the 3rd day. But a gradually increase of collagenation could be observed in PQ group on the 14th day, and it presented a strongly fibrosis. MS group had lower collagen fiber hyperplasia and structure destroy than PQ group. Conclusion Magnesium sulfate could lessen lung injury by reducing the expression of COX - 2, decreasing angiogenesis and inhibiting calcium overload.