肠道蛋白酶在失血性休克大鼠炎症反应中的作用

Effect of prolease in the lumen of rat intestine on inflammatory reaction during hemorrhagic shock

目的通过肠道内灌注蛋白酶抑制剂乌司他丁(UTI),探讨肠道蛋白酶在失血性休克大鼠炎症反应中的作用。方法 28只Wistar大鼠(雌雄不限)随机分为4组:未灌注肠道组(A组)、盐水灌注肠道组(B组)、UTI灌注肠道组(C组)、静脉UTI组(D组)。记录各组大鼠平均动脉压和生存时间的变化,通过流式细胞术检测人粒细胞表面CD11b表达的变化,从而比较不同处理对大鼠血浆活性的影响。采用手工计数法计量不同时间点外周血白细胞数目,最后制作肠道组织病理切片,比较不同组别大鼠肠道黏膜的损害程度。结果 (1)平均动脉压:休克后,C组和D组大鼠血压下降较其他两组缓慢(P<0.05)。(2)生存时间:C组大鼠生存时间明显长于其余3组(P<0.05)。(3)血浆活性:休克后各组大鼠血浆活性均呈增高趋势,但C组活性与其他3组比较明显降低(P<0.05)。(4)外周血白细胞:休克后各组大鼠外周血白细胞总数呈下降趋势,但C组数目与其他3组比较明显升高(P<0.05)。(5)比较空肠黏膜组织病理变化发现,A组黏膜损害程度最深,B、D组次之,C组最轻。结论肠道内灌注蛋白酶抑制剂UTI可以延缓大鼠休克后血压下降过程,减弱血浆活性及炎症反应水平,最终延长生存时间,说明肠道蛋白酶在失血性休克大鼠炎症反应的发生发展中起重要作用。

Objective To investigate the effect of intraluminal administration of ulinastatin （a prolease inhibitor） in the intestine on intestinal inflammation in rats with hemorrhagic shock. Methods Twenty-eight Wistar rats were randomized into control group （A）, intestinal saline perfusion group （B）, ulinastatin intestinal perfusion group （C）, and intravenous ulinastatin injection group （D） （n=7）. The mean arterial blood pressure （MAP） and survival time of the rats were recorded. The changes in human polymorphonuclear cell （PMN） CD11b expression were detected by flow cytometry. The leukocyte count was recorded at different time points after the treatment, and the pathology of the intestinal mucosa was observed comparatively. Results Groups C and D showed significantly slower reduction of the MAP than groups A and B after hemorrhagic shock （P〈0.05）. The survival time of the rats was the longest in group C （P〈0.05）. CD11b expression increased gradually during hemorrhagic shock in all the groups, but the expression level was the lowest in group C （P〈0.05）. Hemorrhagic shock caused a reduction in leukocyte counts, which remained the highest in group C （P〈0.05）. Group C also showed the least intestinal pathology among the 4 groups. Conclusion Intestinal perfusion of ulinastatin can lower the reduction rate of MAP, attenuate plasma activation and intestinal inflammation, and prolong the survival of rats with hemorrhagic shock. These results indicate an important role of prolease in intestinal inflammation during hemorrhagic shock