肠缺血/再灌注对肝脏自由基的影响及亚甲蓝的抗损伤作用

Methylene blue protects liver from injury induced by reactive oxygen species produced during intestinal ischemia/reperfusion

目的 研究肠缺血/再灌注(I/R)后氧自由基(ROS)对远隔器官肝脏的损伤作用,探讨亚甲蓝(MB)抗肝脏损伤的作用机制。方法 新西兰白兔32只,体重2.3～2.9 kg,随机分为4组,(1)正常组:本组仅做假手术处理。(2)I/R组:本组通过夹闭兔肠系膜前动脉1h复制肠I/R模型。(3)治疗A组:本组于松夹后静脉内给予MB 3 mg·kg-1。(4)治疗B组:本组于松夹后静脉内给予MB 15 mg·kg-1。颈总动脉置管,连续监测血压。于夹闭前、松夹即刻、松夹后30 min、1h和2h取血测定血中MDA浓度。实验结束后取一小块肝组织用于测定超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、黄嘌呤氧化酶(XO)及MDA。结果与I/R前基础值比较,I/R组血中MDA水平I/R后显著增加,同时血压显著下降;而治疗A组及B组血中MDA水平于I/R后均未显著增加。与正常组比较,I/R组肝组织MDA水平显著增高,而正常组与两个治疗组间肝组织中MDA无显著差异。结论 MB能减少肠I/R后ROS的生成并能对抗ROS对肝脏的损伤作用。

Objective To investigate the remote liver injury induced by reactive oxygen species (ROS) after intestinal ischemia/reperfusion (I/R) and the mechanism of liver protection afforded by methylene blue (MB) Methods Thirty-two rabbits weighing 2.3-2.9 kg were randomly divided into four groups: (1) normal group in which sham operation was performed; (2) I/R group in which intestinal I/R was produced by clamping anterior mesenteric artery for 1 hour; (3) in treatment group A MB 3 mg·kg-1 was given iv immediately ofter before declamping and (4) in treatment group B MB 15 mg·kg-1 iv was given. Common carotid artery was cannulated for direct continuous blood pressure monitoring. Blood samples were taken before anterior mesenteric artery occlusion, immediately after and 30 min, 1 h and 2 h after decalmping for determination of blood MDA concentration. At the end of the experiment a small piece of hepatic tissue was obtained for determination of its superoxide dismutase (SOD), catalase (CAT), xanthine oxidase (XO) and MDA levels.Results In I/R group blood MDA level increased significantly after I/R as compared with the baseline value before I/R and blood pressure decreased significantly after I/R, while in treatment group A and B there was no significant increase in blood MDA level after I/R. In I/R group liver MDA level was significantly higher than that in normal group, but there was no significant difference in liver MDA level between normal group (group 1) and treatment groups (group 3,4) .Conclusion Methylene blue can reduce the generation of ROS during intestinal I/R and protect liver from ROS-induced injury.