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p38MAPK抑制剂对百草枯致大鼠急性肺损伤的保护作用

发布时间:2018-05-11 15:39

  本文选题:急性肺损伤 + 肺组织肿瘤坏死因子α ; 参考:《医学研究生学报》2014年04期


【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(P0.05);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(P0.05),肺SOD表达水平较PQ组升高[(125.89±6.65)vs(160.24±6.78),(P0.05)]。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。
[Abstract]:Objective Paraquat is highly toxic and lacks effective treatment for poisoning. The protective effect and mechanism of p38 mitogen-activated protein kinase (p38 mitogen-activated protein kinase- p38 MAPK) inhibitor SB203580 on paraquat induced acute lung injury in rats were studied. Methods Seventy-two SD rats were randomly divided into three groups: normal saline group, paraquat PQQ group and p38 inhibitor SB203580 intervention group with 24 rats in each group. After administration, arterial blood gas analysis was performed at different time points. The expression levels of lung tissue wet / dry ratio (W / D), lung tumor necrosis factor 伪 (TNF- 伪), superoxide dismutase (SOD) and lung histopathological changes were observed. Results in the PQ group, the difference of oxygen partial pressure of alveolar artery (PA-aO _ 2) on the 5th day (45.67 卤4.17) in the PQ group was 68.78 卤6.63 卤80.23 卤7.12)mmHg, the expression level of TNF- 伪 in lung tissue was 18.24 卤2.9816.22 卤2.79)pg/mg and W/D(4.913 卤0.0345.020 卤0.045.020 卤0.045.079 卤0.016) and reached its peak on the 3rd day. 鑰孲OD姘村钩浜庣粰鑽悗寮,

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