MAPK通路蛋白在百草枯中毒致急性肺损伤大鼠肺组织中的表达及意义

The expression and significance of MAPK signal proteins in lung tissues of rats with acute lung injury induced by paraquat

目的观察MAPK通路蛋白在百草枯中毒致急性肺损伤大鼠肺组织中的表达并探讨其意义。方法36只SD雄性大鼠随机平均分成两组:PQ组予腹腔注射20 mg/kg百草枯,对照组予腹腔注射生理盐水1 m L。在注射百草枯后8 h、1 d和3 d时,收集血清和肺组织标本。分别使用生化法检测血清中超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量,采用ELISA方法检测血清中白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)含量,利用血气分析仪检测大鼠动脉血氧分压(Pa O2),行组织切片HE染色进行肺损伤评分,利用Western blot方法检测肺组织中p-p38MAPK、p-JNK、p-ERK1/2蛋白表达水平。结果百草枯中毒后,与对照组比较,PQ组大鼠血清中SOD活性降低(P<0.05),MDA、IL-1β和TNF-α含量明显增加(P<0.05);Pa O2逐渐下降(P<0.05),肺损伤评分时间依赖性增加(P<0.05);肺组织中p-p38MAPK、p-JNK、p-ERK1/2表达量均明显上调(P<0.05)。结论百草枯产生氧自由基,可以激活包括p38MAPK、JNK、ERK1/2在内的MAPK通路,导致急性肺损伤发生发展。

Objective To investigate the expression of MAPK signal proteins in lung tissues of rats with acute lung injury induced by paraquat, and to evaluate its significance. Methods A total of 36 male SD rats were distributed to PQ and control groups equally and randomly. The subjects in PQ group were intraperitoneally injected with paraquat （20 mg/kg） and those in control group with saline. Peripheral blood and lung tissues were collected 8 hours, 1 and 3 days after paraquat exposure. The level of MDA, the SOD activity, and the concentrations of TNF - α and IL - 1β were measured via biochemical method and ELISA. Artery PaO2 was assessed with blood gas analyzer. The lung injury scores and the protein levels of MAPK pathway, including p - p38MAPK, p - JNK and p - ERK1/2, were also determined. Results Significant increase of TNF - α , IL - 1β and MDA, and reduction in SOD activity in the peripheral blood were observed in rats of PQ group ; so were the decline of artery PaO2 and elevation of lung injury scores in time - dependent manners. The levels of p - p38MAPK, p - JNK and p - ERK1/2 in lung tissues of rats in PQ group were also significantly increased. Conclusion Reactive oxygen species generated by paraquat can activate MAPK pathway, including p38MAPK, JNK and ERK1/2, leading to the acute lung injury.