p38MAPK抑制剂对百草枯致大鼠急性肺损伤的保护作用  

The protective effect of p38MAPK inhibitor on the paraquat-induced acute lung injury in rats

作　　者：陈娇[1] 聂时南[1] 任艺[1] 孙兆瑞[1] 孙宝迪[1] 邵旦兵[1] 刘红梅[1] 许宝华[1] 唐文杰[1] 张炜[1] 杨志洲[1] 钱晓明[2] 

机构地区：[1]南京军区南京总医院急救医学科,南京医学硕士210002 [2]南京军区南京总医院老年干部二科

出　　处：《医学研究生学报》2014年第4期357-360,共4页Journal of Medical Postgraduates

基　　金：南京军区122工程重点培养对象资助项目(JQZD200905);南京军区南京总医院青年基金(2011030)

摘　　要：目的百草枯毒性强,且缺乏针对中毒的有效治疗手段。文中研究p38丝裂原活化蛋白激酶(p38 mitogen-activated protein kinase,p38MAPK)抑制剂SB203580对百草枯诱导的大鼠急性肺损伤的保护作用及机制。方法 72只SD大鼠按照数字化随机分组法分为3组:等渗盐水(normal saline,NS)组、百草枯(paraquat,PQ)组和p38抑制剂SB203580干预(PQ+SB)组,每组24只。给药后测定不同时间点的动脉血气分析、肺组织湿干比(W/D)、肺组织肿瘤坏死因子α(tumor necrosis factorα,TNF-α)、超氧化物歧化酶(superoxide dismutase,SOD)的表达水平及观察肺组织病理学改变。结果 PQ组给药后1、3、5 d肺泡动脉氧分压差(PA-aO2)[(45.67±4.17)、(68.78±6.63)、(80.23±7.12)mmHg]、肺组织TNF-α表达水平[(14.63±3.10)、(18.24±2.98)、(16.22±2.79)pg/mg]以及W/D(4.913±0.034、5.020±0.064、5.079±0.016)随天数不断升高,并于第3天达到高峰,而SOD水平于给药后开始下降1、3、5 d分别为(175.26±7.98)、(167.57±8.05)、(160.24±6.78)U/μg(P<0.05);与PQ组比较,PQ+SB组PA-aO2[(80.23±7.12)vs(44.17±4.16)]、肺组织TNF-α表达水平[(16.22±2.79)vs(9.48±2.72)]和W/D[(4.805±0.070)vs(5.079±0.016)]均有所下降(P<0.05),肺SOD表达水平较PQ组升高[(125.89±6.65)vs(160.24±6.78),(P<0.05)]。结论 p38MAPK的特异性抑制剂SB203580可以通过减轻炎症反应和提高抗氧化能力来减轻百草枯所致的急性肺损伤反应。Objective Though paraquat （PQ） is highly toxic, there is still no effective treatment for PQ poisoning .The aim of the article was to study the protective effect and mechanism of the p 38 mitogen-activated protein kinase （ MAPK） inhibitor SB203580 on PQ-induced acute lung injury in rats . Methods 72 SD rats were randomly divided into three groups （ n=24 ）： normal saline （NS） group, PQ poisoning group and p38 inhibitor SB203580 intervention （PQ＋SB） group.The arterial blood gas analysis, lung wet and dry ratio （W/D）,the expression of tumor necrosis factor-α（TNF-α）, the superoxide dismutase （SOD） level and the pathological changes of lung tissues were recorded at different time points after drug intervention . Results On the 1st , 3rd, 5th days after drug intervention in PQ group, the alveolo-arterial oxygen partial pressure difference （PA-aO2） [（45.67 ±4.17）, （68.78 ±6.63）, （80.23 ±7.12 ） mmHg ], the lung tissue TNF-αexpression （14.63 ±3.10], [18.24 ±2.98], [16.22 ±2.79] pg/mg） and W/D （[4.931 ±0.034], [5.020 ±0.064], [5.079 ±0.016]） in-creased gradually to a peak on the 3rd day, while the SOD level de-creased respectively on the 1st , 3rd, 5th days after drug intervention （[175.26 ±7.98], [167.57 ±8.05], [160.24 ±6.78] U/ug） （P＆lt;0.05）.Compared with PQ group, PQ＋SB group got a decrease in the PA-aO2（[80.23 ±7.12] vs [44.17 ±4.16]）, the lung tissue TNF-αexpression （[16.22 ±2.79] vs [9.48 ±2.72]） and W/D （[4.805 ±0.070] vs [5.079 ±0.016]） （P＆lt;0.05）, while the pulmonary SOD level increased in comparison with PQ group （[125.89 ±6.65] vs [160.24 ±6.78]） （P＆lt;0.05）. Conclusion The p38MAPK inhibitor SB203580 plays a certain protective role in PQ-induced acute lung injury by reducing inflammation and improving antioxidant capacity .

关 键 词：急性肺损伤 肺组织肿瘤坏死因子α 超氧化物歧化酶 SB203580 P38丝裂原活化蛋白激酶 TNF-α 

分 类 号：R56[医药卫生—呼吸系统]