缺血前应用肥大细胞脱颗粒剂减轻小鼠小肠再灌注损伤

目的观察缺血前使用肥大细胞脱颗粒剂Compound 48/80(CP)]对小肠缺血-再灌注损伤的影响及机制。方法健康清洁级雄性昆明小鼠,随机分为三组:假手术组、缺血-再灌注组及CP缺血前处理组。在缺血前15 min分别静脉注射CP 1 mg/kg(CP缺血前处理组)或等量生理盐水(假手术组及缺血-再灌注组)后,缺血-再灌注组与CP缺血前处理组建立小肠缺血30 min再灌注损伤模型,观察再灌注3天内动物存活率的变化;并评价再灌注3 h小肠病理损伤变化及检测肥大细胞蛋白激酶4(MCP-4)、血浆内皮素-1(ET-1)、肿瘤坏死因子(TNF-α)及白细胞介素-6(IL-6)浓度与类胰蛋白酶蛋白表达及过氧化物酶(MPO)活性。结果缺血-再灌注组的生存率较假手术组明显降低(p<0.05);CP缺血前处理组生存率明显高于缺血-再灌注组(p<0.05)。与假手术组比较,缺血-再灌注组小肠损伤评分、ET-1、TNF-α及IL-6浓度及MPO活性显著升高(p<0.05);缺血-再灌注组类胰蛋白酶与MCP-4表达较假手术组明显升高(p<0.05)。与缺血-再灌注组比较,CP缺血前处理组上述指标显著降低(p<0.05);而MCP-4表达进一步升高(与缺血-再灌注组比较,p<0.05)。结论缺血前应用肥大细胞脱颗粒剂能够减轻小肠缺血-再灌注损伤,可能与肥大细胞释放MCP-4有关。

MAST CELL DEGRANULATION PRIOR TO ISCHEMIA ATTENUATES SMALL INTESTTINAL ISCHEMIA REPERFUSION INJURY IN MICE

Objective To investigate the protective role of mast cell degranulation prior to ischemia in small intestinal iscbemia reperfusion injury（IIRI） in mice. Methods Adult Kunming mice were randomized into sham operated group （SH group）, sole IIR group（ M group） in which mice were subjected to 30 min superior mesenteric artery occlusion followed by 3 bours or 3 days reperfusion, or IIR being respectively intravenously injected with Compound 48/80（ 1 mg· kg^-1 ） 15 minutes prior to ischemia（PreCP group）. Survival rates during 3 days were observed, and at the 3 h after reperfusion, the small intestine was obtained for histologic injury assessment, protein expressions of tryptase and mast cell protease 4 （ MCP - 4 ） in small intestine were measured, levels of ET - 1, TNF - α, and IL - 6 and MPO activity in the intestine were measured. Resuits IIR resuhed in small intestine injury manifested as significant increases in mortality as well as intestine histological seores（p 〈 0.05 ） , accompanied with concomitant increases of tryptase and MCP - 4 protein expressions and elevations in ET- 1, TNF-α and IL- 6 concentrations and MPO activity in small intestine as compared with SH group（p 〈 0. 05 ）. Administration with Compound 48/80 15 rain prior to ischemia markedly reduced the above biochemical changes （p 〈 0. 05 vs M）, moreover, MCP- 4 expression was significant higher in PreCP group than that in M group （p 〈 0. 05 ）. Conclusion Mast cell degranulation prior to iscbemia contributes to better therapeutic benefits in attenuating IIR injury in mice possibly by releasing MCP - 4.