肝缺血预处理保护作用与一氧化氮/内皮素-1系统有关

The protection of the hepatic ischemic preconditioning is concerned with the NO/ET-1 system

目的 :研究一氧化氮 /内皮素 - 1(NO/ET - 1)失衡与肝缺血再灌注 (I/R)损伤的关系以及肝缺血预处理 (IPC)对NO/ET - 1系统的调节作用。方法 :采用鼠肝I/R模型 ,比较I/R组和IPC +I/R组NO/ET - 1系统的变化情况及其与肝I/R损伤的关系。用RT -PCR检测再灌注 2h内肝组织中是否有诱生性一氧化氮合酶(iNOS)mRNA表达。结果 :再灌注急性期血浆NO代谢产物 (NO-2 /NO-3 )降低、ET - 1升高致NO/ET - 1比值降低 ,血浆ALT、AST、LDH、TNF -α含量及肝组织丙二醛 (MDA)含量增高 ,而肝组织ATP含量降低 ,肝损伤加重 ;肝IPC的保护作用与其升高NO-2 /NO-3 、降低ET - 1,升高NO/ET - 1比值有关 ;在上述肝组织中未测出有iNOSmR NA表达。结论 :肝I/R损伤与NO/ET - 1失衡有关 ,IPC对I/R急性期肝的保护作用可能是通过对NO/ET - 1系统的调节作用而介导的 ,此时NO来源于原生性一氧化氮合酶 (cNOS)

AIM: To study the relationship between the disturbance of nitric oxide/endothelin-1(NO/ET-1) and hepatic ischemia/reperfusion(I/R) injury as well as the regulation of NO/ET-1 system by hepatic ischemic preconditioning(IPC). METHODS: The changes of NO/ET-1 system and their relationship with hepatic I/R injury were compared between I/R group and IPC+I/R group in a rat hepatic I/R model. Two hours after reperfusion, the liver tissues were detected by RT-PCR to see whether there was inducible nitric oxide synthase (iNOS) mRNA expression. RESULTS:In the acute phase of hepatic reperfusion, the ratio of NO/ET-1 was reduced, which was due to a significant reduction of NO - 2/NO - 3 (the metabolic product of NO) and significant elevation of ET-1 in the blood plasma. The content of ALT, AST, LDH and TNF-α in blood plasma, and of MDA in liver tissue were increased but ATP in liver tissue was reduced, the hepatic damage was deteriorated. The protection of the hepatic IPC was concerned with the elevation of the ratio of NO/ET-1 caused by the elevation of NO - 2/NO - 3, and reduction of ET-1 as well. There was no iNOS mRNA detected in the liver tissues.CONCLUSION: Hepatic I/R injury is related to the disturbance of NO/ET-1. The protection of the hepatic IPC in the acute phase might be conducted by its regulation of NO/ET-1 system. The cNOS rather than the iNOS generated the NO in this situation.