延迟相肢体缺血预处理抑制MAPKs磷酸化减轻兔肝缺血再灌注损伤  

Limb ischemic preconditioning reduces rabbit hepatic ischemia-reperfusion injury through inhibition the phosphorylation of proteins in the MAPK signal pathway in the late phase

作　　者：曹丽君[1] 袁贵秀[1] 王亚平[1] 常业恬[1] 徐军美 邹定全[1] 魏来[1] 

机构地区：[1]中南大学湘雅二医院麻醉科,长沙410011

出　　处：《中南大学学报（医学版）》2012年第6期591-597,共7页Journal of Central South University ：Medical Science

摘　　要：目的:研究肢体缺血预处理延迟相对缺血再灌注损伤肝丝裂原活化蛋白激酶家族P38MAPK,P44/P42MAPK和JNK磷酸化水平的影响。方法:健康成年雄性新西兰大白兔36只,随机分为假手术对照组(C组)、缺血再灌注组(IR组)、肢体缺血预处理组(L组),每组12只。C组行假手术;IR组阻断肝十二指肠韧带25 min,再灌注3 h;L组先分离双后肢股动静脉,阻断5 min后开放10 min,重复3次,24 h后阻断肝十二指肠韧带25 min,再灌注3 h。检测血浆ALT水平,观察肝组织与细胞的结构变化。于再灌注30 min时每组随机取5只兔的左肝外叶肝组织,Western印迹检测肝组织P38,P44/P42和JNK蛋白激酶磷酸化水平变化。结果:与C组比较,再灌注后IR组、L组兔血浆ALT显著升高(P<0.01),但L组升高程度小于IR组(P<0.01)。光镜与电镜结果显示再灌注3 h,IR组肝细胞大小不一,变性坏死,肝血窦扩张,大量红细胞淤滞,明显可见炎性细胞浸润,肝小叶结构破坏;L组肝细胞水肿,有少量变性坏死,炎性细胞散在浸润,但肝小叶结构存在。缺血再灌注30 min兔肝组织磷酸化P38MAPK,P44/P42 MAPK和JNK较C组明显升高(P<0.01),但L组JNK,P38MAPK磷酸化水平明显低于IR组(P<0.05)。结论:肢体缺血预处理对肝缺血再灌注有延迟性保护作用,其机制与抑制缺血再灌注肝组织JNK,P38蛋白激酶的磷酸化有关。Objective： To investigate the liver protection mechanisms of MAPK signaling pathway of limb ischemia preconditioning in the late phase.Methods： Thirty-six adult male New Zealand white rabbits, weighing 1.8-2.0 kg, were randomly divided equally into 3 groups： group C （sham operation）, group L （liver ischemia-reperfusion 24 h after limb ischemia preconditioning）, group IR （liver ischemia-reperfusion without limb ischemia preconditioning）. Serum alanine transaminase （ALT） was measured during ischemia reperfusion. Thetissue and cell injury of liver were examined by optical and electron microscopy. Activation of P38MAPK, P44/P42MAPK, andJNK in hepatic tissue was assessed by western blot after 30 min ofreperfusion.Results： Serum ALT and cell injury in the liver as examined by optical and electron microscopy was decreased in group L as compared with the group IR. Phosphorylation of P38MAPK, P44/ P42MAPK, and JNK were all increased significantly after 30 rain of reperfusion. Phosphorylation of P38MAPK andJNK was reduced by limb ischemia pre-treatment.Conclusion： Limb ischemia pre-treatment can induce the late phase of preconditioning in rabbit liver through the inhibition of the phosphorylation ofP38MAPK andJNK.

关 键 词：肢体缺血预适应 延迟相 丝裂原活化蛋白激酶 信号转导通路 

分 类 号：R363[医药卫生—病理学]