肢体缺血预处理大鼠肝损伤保护效应中内皮素1的变化和意义

背景：研究体内最强的缩血管物质内皮素1在肢体缺血预处理保护大鼠肢体缺血再灌注后肝损伤中的变化和意义，有助于从肝脏微循环角度探讨肢体缺血预处理的保护作用。 目的：探讨内皮素1在肢体缺血预处理保护大鼠肢体缺血再灌注后肝损伤中的变化和意义。 方法：雄性Wistar大鼠随机分为对照组、肢体缺血再灌注组和肢体缺血预处理组。肢体缺血预处理组以橡皮带预先阻断双后肢血流5 min，然后恢复血流灌注5 min，反复4次进行缺血预处理。然后肢体缺血再灌注组和肢体缺血预处理组以橡皮带环绕结扎大鼠双后肢根部，阻断血流4 h后松解，恢复血流灌注4 h制备肢体缺血再灌注模型，并于再灌注前20 min于左侧颈外静脉插管滴注生理盐水。对照组双后肢松弛环绕橡皮带但不阻断血流，其后操作同肢体缺血再灌注组。 结果与结论：大鼠肢体缺血再灌注后血浆内皮素1、透明质酸酶、丙二醛、谷丙转氨酶、谷草转氨酶水平和肝组织内皮素1、丙二醛、髓过氧化物酶水平均明显升高(P < 0.05)，肢体缺血预处理干预后上述指标均明显降低(P < 0.05)。光镜下可见肢体缺血再灌注组肝细胞肿胀，肝索排列不规则；肢体缺血预处理组上述损伤表现减轻。结果可见大鼠肢体缺血预处理对肢体缺血再灌注后肝损伤的保护作用可能与抑制了内皮素1的缩血管作用从而改善肝脏的微循环有关，也可能与内皮素1含量的降低减少了白细胞过度聚集活化和减弱脂质过氧化有关。

Changes of endothelin-1 in the protective effect of limb ischemia preconditioning on hepatic injury following limb ischemia reperfusion in rats

BACKGROUND:Endothelin-1 is the strongest vasoconstrictor substance in vivo. To study the changes of endothelin-1 in limb ischemia preconditioning against hepatic injury following limb ischemia reperfusion in rats may help us to evaluate the protective effect of limb ischemia preconditioning on hepatic injury from the aspect of the hepatic microcirculation. OBJECTIVE:To evaluate the changes of endothelin-1 in the protective effect of limb ischemia preconditioning on hepatic injury following hind limbs ischemia reperfusion in rats. METHODS:Male Wistar rats were divided into three groups (n=8): control group, limb ischemia-reperfusion group and limb ischemia preconditioning group. The rat in the limb ischemia-reperfusion group were performed with pre-blocking pairs of hind limb blood flow for 5 minutes with rubber, and then restored the perfusion for 5 minutes, repeated the ischemic preconditioning for four times. In the limb ischemia-reperfusion group and limb ischemia preconditioning group, the rat hind limb roots were ligated by rubber band, the blood flow was released after blocked for 4 hours, and then the blood flow perfusion was restored for 4 hours to prepare the limb ischemia-reperfusion model. The rats were infused with saline through left external jugular vein catheterization at 20 minutes before reperfusion. In the control group, the rat hind limbs were loosely circled with the rubber band but not to block the blood flow, and the following procedures were same to the operation in the limb ischemia-reperfusion group and limb ischemia preconditioning group. RESULTS AND CONCLUSION:The levels of endothelin-1, hyaluronic acid (HA), malondialdehyde (MDA), alanine transaminase (ALT) and aspartate transaminase (AST) in plasma and the contents of endothelin-1, MDA and myeloperoxide (MPO) in liver tissue were increased following LIR (P < 0.05); Compared with the limb ischemia-reperfusion group, the levels of endothelin-1, HA, MDA, ALT and AST in plasma and the contents of endothelin-1, HA, MDA and MPO in liver tissue were significantly decreased (P > 0.05) in the limb ischemia preconditioning group. The results of the light microscope clued that the hepatic cells swelling and the hepatic funiculus were irregular in the limb ischemia-reperfusion group while the liver injury were alleviated in the limb ischemia preconditioning group. The protection effect of limb ischemia preconditioning on hepatic injury following limbs ischemia reperfusion in rats may relate to the improvement of microcirculation in the liver by restraining the vasoconstrictive action of endothelin-1, which is perhaps related to improving the aggregation of neutrophil and alleviating the damage of the lipid peroxidation following the low content of endothelin-1.