咪达唑仑预先给药对小鼠肠缺血再灌注时炎性反应和细胞凋亡的影响

Effects of midazolam pretreatment on inflammatory responses and cell apoptosis during intestinal ischemia-reperfusion in mice

目的 评价咪达唑仑预先给药对小鼠肠缺血再灌注时炎性反应和细胞凋亡的影响.方法 清洁级健康雄性昆明小鼠30只,体重18～22 g,采用随机数字表法分为3组（n=10）：假手术组（S组）、肠缺血再灌注组（I/R组）和咪达唑仑预先给药组（M组）.采用夹闭肠系膜上动脉20 min恢复灌注的方法制备小鼠肠缺血再灌注损伤模型.M组腹腔注射咪达唑仑1 mg/kg,30 min后制备模型.于再灌注24 h时处死小鼠,取小肠,采用Chiu评分法测定肠黏膜损伤程度,采用免疫组化法测定IL-6、TNF-α和caspase-3的表达.结果 与S组比较,I/R组和M组小鼠肠组织Chiu评分升高,IL-6、TNF-α和caspase-3表达上调（P＜0.05）;与I/R组比较,M组小鼠肠组织Chiu评分降低,IL-6、TNF-α和caspase-3表达下调（P＜0.05）.结论 咪达唑仑预先给药可减轻小鼠肠缺血再灌注损伤,其机制与抑制炎性反应和细胞凋亡有关.

Objective To evaluate the effects of midazolam pretreatment on inflammatory responses and cell apoptosis during intestinal ischemia-reperfusion （I/R） in mice.Methods Thirty healthy male Kunming mice,weighing 18-22 g,were equally and randomly divided into 3 groups using a random number table：sham operation group （S group）,I/R group,and midazolam pretreatment group （M group）.Intestinal I/R was produced by occlusion of the superior mesenteric artery for 20 min followed by reperfusion.In group M,midazolam 1 mg/kg was injected intraperitoneally,and intestinal I/R was produced 30 min later.At 24 h of reperfusion,the mice were sacrificed,and intestinal tissues were removed for microscopic examination and for determination of the expression of interleukin-6 （IL-6）,tumor necrosis factor-alpha （TNF-α） and caspase-3.Intestinal damage was assessed and scored according to Chiu.Results Compared with group S,Chiu＆#39;s scores were significantly increased,and the expression of IL-6,TNF-α and caspase-3 was significantly up-regulated in I/R and M groups （P〈0.05）.Compared with group I/R,Chiu＆#39;s scores were significantly decreased,and the expression of IL-6,TNF-α and caspase-3 was significantly down-regulated in group M （P〈0.05）.Conclusion Midazolam pretreatment can reduce intestinal I/R injury,and the mechanism is related to inhibition of inflammatory responses and cell apoptosis in mice.