地塞米松不同时期给药对小鼠肠缺血再灌注损伤及诱导型一氧化氮合酶活性的影响

目的 评价地塞米松不周时期给药对小鼠肠缺血再灌注损伤及诱导型一氧化氮合酶(iNOS)活性的影响.方法 健康清洁级雄性昆明小鼠35只,体重20～24 g,采用随机数字表法,将其随机分为5组(n=7):假手术组(Ⅰ组)、肠缺血再灌注组(Ⅱ组)、地塞米松缺血前给药组(Ⅲ组)、地塞米松缺血期给药组(Ⅳ组)和地塞米松再灌注即刻给药组(Ⅴ组).采用阻断肠系膜上动脉30 min再灌注的方法制备肠缺血再灌注损伤模型.Ⅰ组只分离肠系膜上动脉,不阻断；Ⅱ组和Ⅲ组分别在缺血前30 min经尾静脉注射生理盐水和地塞米松10 mg/kg；Ⅳ组于缺血5 min时、Ⅴ组于再灌注即刻静脉注射地塞米松10 mg/kg.再灌注3h时处死小鼠,取小肠组织,光镜下观察小肠粘膜病理学结果,采用Chiu评分法对小肠病理损伤进行评分；采用硝酸还原酶法检测一氧化氮(NO)含量,采用比色法检测iNOS的活性.结果 与Ⅰ组比较,Ⅱ组～Ⅴ组肠组织Chiu评分、Ⅱ组、Ⅳ组和Ⅴ组肠组织iNOS活性和NO含量升高(P＜0.05),Ⅲ组肠组织iNOS活性和NO含量差异无统计学意义(P＞0.05)；与Ⅱ组比较,Ⅲ组肠组织Chiu评分、iNOS活性和NO含量降低,Ⅴ组肠组织Chiu评分、iNOS活性和NO含量均升高,Ⅳ组上述指标差异无统计学意义(P＞0.05).结论 地塞米松缺血前给药可减轻小鼠肠缺血再灌注损伤,缺血期给药对损伤无明显影响,再灌注即刻给药可加重损伤,可能与地塞米松不同时期用药对iNOS活性影响不同有关.

Effects of dexamethasone administration at different times on intestinal ischemia-reperfusion injury and inducible nitric oxide syntlase activity in mice

Objective To evaluate the efffects dexamethasone (DEX) administration at different times on intestinal ischemia-reperfusion(I/R) injury and inducible nitric oxide synthase(iNOS) activity in mice.Methods Tirty-five healthy male Kunming mice weighing 20-24 g were randomly divided into 5 groups( n =7 each): Sham operation group (group Ⅰ ); intestinal I/R group (group Ⅱ ); DEX administration before ischemia group (group Ⅲ ); DEX administration during ischemia group ( group Ⅳ) and DEX administration at the begining of reperfusion group (group Ⅴ ).Intestinal I/R injury was induced by clamping the superior mesenteric artery for 30 min.Normal saline10 mg/kg,DEX 10 mg/kg was injected iv at 30 min before ischemia in groups Ⅱ and Ⅲ respectively.DEX 10 mg/kg was injected iv at 5 min of ischemia in groupⅣ and immediately at the begining of reperfusion in group Ⅴ.The mice were sacrificed at 3 h of reperfusion,and then the small intestinal tissues were taken for determination of intestinal pathological score( Chiu score),iNOS activity and nitric oxide (NO) content.Results Chiu score was significantly higher in groups Ⅱ - Ⅴ,and iNOS activity and NO content were sinificantly higher in groups Ⅱ,Ⅳ and Ⅴ than in group Ⅰ ( P ＜ 0.05).Chiu score,iNOS activity and NO content were sinificantly lower in group Ⅲ,and were higher in group Ⅴ than in group Ⅱ ( P ＜ 0.05).There was no significant difference in the indexes mentioned above between groups Ⅱ and Ⅳ ( P ＞ 0.05).Conclusion DEX administration before ischemia can reduce intestinal I/R injury by inhibiting iNOS activity; DEX administration during ischemia has no effcet on intestinal I/R injury and iNOS activity; DEX administration at the begining of reperfusion aggravates intestinal I/R injury by enhancing iNOS activity.