一氧化氮和内皮素在肝脏再灌注损伤和缺血预处理中作用的研究

Involvement of nitric oxide(NO) and endothelin(ET) in ischemia-reperfusion injury and its role in preconditioning

目的 :观察缺血预处理一氧化氮 (NO)和内皮素 (ET)的变化及其与再灌注损伤和微循环变化的关系。方法 :建立大鼠肝脏 70 %缺血再灌注损伤模型 ,分为对照组、缺血组、缺血预处理组、L 精氨酸组、L NAME组 ,观察各组肝功能变化 ,检测肝组织和血清中NO和ET及透明质酸 (HA)的水平 ,以HA代表肝脏微循环情况。结果 :再灌注损伤后微循环的破坏和NO和ET的变化相关 ,缺血预处理可减少NO水平的下降和血浆ET升高 ,减少微循环破坏和肝功酶的升高 (P <0 .0 5 )。外源性给予NO合成前体L 精氨酸在升高NO水平降低ET水平的同时 ,可达到类似预处理的保护作用。结论 :血管活性介质NO的减少和ET水平增加是导致再灌注损伤微循环变化的原因之一。缺血预处理可诱导增加NO和减少ET ,并可能是其改善微循环和减少再灌注损伤的因素之一。给予外源性NO可起到类似缺血预处理的保护效果 ,而抑制NO产生并不能加重再灌注损伤。

Objective: To evaluate the relationship between expression of nitric oxide(NO) and endothelin(ET) and microcirculation in ischemia-reperfusion injury.Methods:70% hepatic ischemia-reperfusion (60-40min) model was performed in male Wister rats,and divided in five groups,or Sham,non-IPC,ischemic preconditioning (IPC 5min ),L-arginine,and N(G)-nitro-L-arginine methyl esther (L-NAME) group.Serum and tissue NO were examied by Griess method,and serum ET and hyaluronic acid(HA) were examied by radioimmological assay.Serum HA was used to reflect microcirculation state. Results:After ischemia-reperfusion,the level of NO in serum and liver tissue was decreased and ET was increased,accompanied by microcirculation disturbance (P<0.05).While preconditioning (IPC 5min ) increased NO production,decreased ET,accompanied by inhibition of the increase of ALT,AST, and HA.NO donor L-arginine had the similar protection as preconditioning,also increasing NO production.Conclusion:NO/ET imbalance may be the one cause of microcirculation disturbance after reperfusion injury.The improvement of NO production and decreased ET production after preconditioning,may be the cause of the protection of preconditioning.Drug that can induce the production of NO may has protection as preconditioning,which may be used as a method of drug-preconditioning.