摘要
目的:探讨p38丝裂原活化蛋白激酶抑制剂SB203580对创伤失血性休克致急性肺损伤大鼠的影响。方法:30只SPF级健康雄性SD大鼠随机分为3组(n=10):假手术组(S组)、急性肺损伤模型组(M组)和急性肺损伤模型组+SB203580组(SB组)。M组和SB组建立急性肺损伤模型,SB组造模前30 min静脉注射抑制剂SB203580(2mg/kg)。股动脉穿刺置管监测平均动脉压(MAP)和心率(HR);创伤后6h采集动脉血样进行血气分析;采用ELISA法测定血清TNF-α、IL-6和IL-1β的水平;收集肺泡灌洗液(BALF)行中性粒细胞细胞(PMN)计数;比色法测定肺组织髓过氧化物酶(MPO)活性;光镜和电镜下观察肺组织病理学改变,采用Western blot法检测p38丝裂原活化蛋白激酶(p38MAPK)的表达。结果:创伤失血性休克后2h和4h时间点,大鼠心率和平均动脉血压显著下降,静脉注射SB203580后大鼠心率和平均动脉血压相对平稳。与S组比较,M组大鼠pH和PaO2降低,PaCO2、BALF中中性粒细胞细胞计数、MPO活性和血清TNF-α、IL-6及IL-1β的水平升高,肺组织p38MAPK的表达上调(P<0.05);与M组比较,SB组大鼠pH和PaO2升高,PaCO2、BALF中中性粒细胞细胞计数、MPO活性和血清TNF-α、IL-6及IL-1β的水平降低,肺组织p38MAPK的表达下调(P<0.05)。结论:p38MAPK抑制剂SB203580可减少肺组织中的p38MAPK的表达,降低血清中的TNF-α、IL-6和IL-1β的水平,从而减轻创伤失血性休克导致的急性肺损伤。
Objective： To investigate the effects of p38 MAPK inhibitor on acute lung injury induced by trauma-hemorrhagic shock in rats. Methods： Thirty SPF male rats were randomly assigned into three equal groups （n=10）： sham procedure （S） group, acute lung injury model （M） group, a- cute lung injury model and specific p38MAPK inhibitor SB203580 treatment （SB） group. M and SB groups were established the animal model of acute lung injury. SB group rats were infused with SB203580 for 2 mg/kg in 30 rain before performing model establishment. The left femoralartey was cannulated to monitor mean arterial pressure and heart rates; At 6 h after trauma, arterial blood was drawn for blood gas analysis. The levels of TNF-α, IL-6 and IL-1β in the serum were measured using enzyme-linked immunosorbent assays （ELISA）. PMN percentage in bronchoalveolar lavage fluid （BALF） were measured. Lung tissue myeloperoxidase （MPO） activation was determinated by Colorimetric assay. Lung tissue samples were collected to examine pulmona- ry pathologic changes were observed under light microscopy and electron microscopy, p38MAPK protein expressions were assessed by Western blot. Results： At 2 and 4 h, MAP and HR was significantly decreased in T/HS rats （P〈0.05） versus S group, whereas fluctuation in MAP and HR was relatively stable following the infusion of 2 mg/kg SB203580. Compared with group S, pH and PaO2 were significantly decreased; PaCO2, PMN percentage in BALF, MPO activation and TNF-α, IL-6, IL-1β levels in serum were increased and p38MAPK expressions were significantly increased in lung tissue （P〈0.05）. Compared with group M, pH and PaO2 were significantly decreased, PMN percentage in BALF, MPO activation and TNF-α, IL-6, IL-1β levels in serum were decreased and p38MAPK expressions were significantly decreased in lung tissue （P〈 0. 05）. Conclusion： p38MAPK inhibitor SB203580 could decrease acute lung injury induced by trauma-hemorrhagic shock in rat through reducing the expression
出处
《武汉大学学报（医学版）》
CAS
2015年第6期857-861,871,共6页
Medical Journal of Wuhan University
基金
中央高校基本科研业务费专项资金(编号:2042014kf0146)
关键词
丝裂原活化蛋白激酶
创伤
休克
出血性
急性肺损伤
Mitogen Activated Protein Kinases
Trauma
Shock
Hemorrhagic
Actue Lung Injury
