Wang Bao-Qiang, Kan Yong-Feng, Yang Quan-Hui
Department of General Surgery, Beijing Shijingshan Hospital, Beijing 100043, China.
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2010 Aug;26(3):376-9.
To study the relationship between the disturbance of nitric oxide/endothelin-I (NO/ET-1) and the hepatic injury following limb ischemia/reperfusion (I/R) in rats as well as the regulation of NO/ET-1 system by limb ischemia preconditioning (IPC).
Using limb ischemia/reperfusion injury model rats, animals were randomly divided into three groups (n = 6): control group, I/R group and IPC group. The contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST) in the plasma as well as nitric oxide (NO), endothelin-1 (ET-1), nitric oxide/endothelin-1 (NO/ET-1) in the plasma and the liver were measured. The levels of total nitric oxide synthase (tNOS), inducible nitric oxide synthase (iNOS), constitutive nitric oxide synthase (cNOS) in the liver were determined. The expression of iNOS and endothelial NOS (eNOS) were detected by the immunohistochemical method. The morphologic changes stained with hematoxylineosin were observed under microscope.
It was found that the levels of NO, ET-1 in the plasma and the liver tissue all increased after reperfusion, while the values of ALT, AST, NO/ET-1 decreased. Liver pathology revealed that after limb I/R there were edema, villous microvascular congestion, infiltration of polymorphonuclear neutrophil (PMN), cell degeneration in part cells of the liver. The hepatic damage was deteriorated. While the expression of iNOS elevated, cNOS (mainly eNOS) reduced and total NOS increased. The protection of the limb IPC attenuated the disturbance of NO/ET-1.
The hepatic injury following limb I/R is related to the disturbance of NO/ ET-1. The protection of the limb IPC might be conducted by its regulation of NO/ET-1 system. The elevation of endothelial NOS and the reduction of non-endothelial NOS generated the NO in this situation.
研究一氧化氮/内皮素-1（NO/ET-1）失衡与大鼠肢体缺血/再灌注（I/R）后肝损伤的关系，以及肢体缺血预处理（IPC）对NO/ET-1系统的调节作用。
采用肢体缺血/再灌注损伤模型大鼠，将动物随机分为三组（n = 6）：对照组、I/R组和IPC组。检测血浆中丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）以及血浆和肝脏中一氧化氮（NO）、内皮素-1（ET-1）、一氧化氮/内皮素-1（NO/ET-1）的含量。测定肝脏中总一氧化氮合酶（tNOS）、诱导型一氧化氮合酶（iNOS）、组成型一氧化氮合酶（cNOS）的水平。采用免疫组织化学方法检测iNOS和内皮型一氧化氮合酶（eNOS）的表达。苏木精-伊红染色后在显微镜下观察形态学变化。
发现再灌注后血浆和肝组织中NO、ET-1水平均升高，而ALT、AST、NO/ET-1值降低。肝脏病理学显示，肢体I/R后肝脏出现水肿、绒毛状微血管充血、多形核中性粒细胞（PMN）浸润、部分肝细胞变性。肝损伤加重。同时iNOS表达升高，cNOS（主要是eNOS）降低，总NOS增加。肢体IPC的保护作用减轻了NO/ET-1的失衡。
肢体I/R后的肝损伤与NO/ET-1失衡有关。肢体IPC的保护作用可能是通过调节NO/ET-1系统实现的。在这种情况下，内皮型一氧化氮合酶升高和非内皮型一氧化氮合酶降低产生了NO。
