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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 effect of p38 mitogen-activated protein kinase inhibitor SB203580 on acute lung injury induced by traumatic hemorrhagic shock in rats. Methods: Thirty healthy SPF male SD rats were randomly divided into three groups (n = 10): sham operation group (S group), acute lung injury model group (M group) and acute lung injury model group + SB203580 group group). Acute lung injury model was established in M group and SB group, and SB203580 (2 mg / kg) was injected intravenously 30 minutes before model group in SB group. The arterial blood pressure (MAP) and heart rate (HR) were monitored by femoral artery catheterization. Arterial blood samples were collected 6h after trauma for blood gas analysis. Serum levels of TNF-α, IL-6 and IL-1β were measured by ELISA. (PMN) were counted in the lotion (BALF); the activity of myeloperoxidase (MPO) in lung tissue was measured by colorimetric method; the pathological changes of lung tissue were observed under light microscope and electron microscope; Mitogen-activated protein kinase (p38MAPK) expression. Results: After 2h and 4h of traumatic hemorrhagic shock, the heart rate and mean arterial blood pressure of rats decreased significantly. The heart rate and mean arterial pressure of rats after SB203580 intravenous injection were relatively stable. Compared with group S, the pH and PaO2 of group M were decreased, the number of neutrophil cells, the activity of MPO and the level of TNF-α, IL-6 and IL-1β were increased in PaCO2 and BALF, and the expression of p38MAPK (P <0.05). Compared with M group, the pH and PaO2 of SB group increased, the level of PaCO2 and neutrophil count, MPO activity and the level of serum TNF-α, IL-6 and IL-1β in BALF Decreased, the expression of p38MAPK in lung decreased (P <0.05). CONCLUSIONS: p38MAPK inhibitor SB203580 can reduce the expression of p38MAPK in lung tissue and decrease the levels of TNF-α, IL-6 and IL-1β in serum and thus reduce the acute lung injury induced by traumatic hemorrhagic shock.