二氮嗪对黄疸大鼠肝脏缺血再灌注损伤的影响

The Influence of Diazoxide on Obstructive Jaundice Liver Suffering ischemia and Reperfusion Injury

目的:研究二氮嗪对梗阻性黄疸肝脏的缺血再灌注损伤是否有保护作用。方法:采用胆总管结扎法制作梗阻性黄疸模型,雄性S-D大鼠60只,分5组:缺血再灌注损伤组(对照组),缺血30 min和再灌注120 min:GSH活性氧(清除剂)处理组,缺血再灌注前10 min静脉注射GSH 50 mg/kg;二氮嗪预处理组(A、B、c)缺血再灌注前10 min分别静脉注射1 mg/kg、5 mg/kg、10 mg/kg。结果:与时照组相比,二氮嗪预处理各组血清中ALT、AsT、LDH含量,细胞内MDA含量和SOD活性,肝细胞凋亡指数差异无显著性(P>0.05),而GSH组与对照组相比,各组血清中ALT、AST、LDH含量,细胞内MDA含量和SOD活性,肝细胞凋亡指数差别具有显著性(P<0.05)。结论:二氮嗪预处理对大鼠梗阻性黄疸肝脏缺血30 min再灌注120 min无保护作用,GSH预处理对大鼠梗阻性黄疸肝脏缺血再灌注损伤能提供保护作用。

Objective The main aim of this study was to determine whether Diazoxide preconditioning, a selective opener of mitochondrial potassium （mitoKATP） channel, can mediate protection of obstructive jaundice liver on S-D rats suffering ischemia and reperfusion （I/R） injury. Methods 60 obstructive jaundice S-D rats were divided into 5 groups of 12 animals each randomly：The control group, Diazoxide preconditioning A, B, C and GSH group . Obstructive jaundice rats were performed with 30 min ischemia followed by 120 min reperfusion. The Diazoxide groups were pretreated with 1 mg/kg, 5 mg/kg and 10 mg/kg of Diazoxide respectively 10 min before the 30 min ischemia and 120 min reperfusion injury while another group was pretreated with GSH, an ROS scavenger, 50 mg/kg 10 min before the 30 min ischemia and 120 rain reperfusion injury. Blood samples were collected for measurement of serum values of ALT, AST, LDH . The malondialdehyde （MDA） , superoxide dismutase （SOD） in hepatic cells, and apoptosis index （AI） were analyzed. Results Compared with the control group, there is no significant statistical difference in the serum about AST, ALT, LDH, the malonyldialdehyde （MDA） contents, superoxide dismutase （SOD） in hepatic cells and apoptosis index （AI） as well. However, Compared with the control group, there is significant statistical difference if GSH was added . Conclusions Chemical preconditioning with selective mitoKATP channel opener Diazoxide, has no significant protective effect on obstructive jaundice liver followed by 30 min ischemia and 120 min reperfusion injury. ROS scavenger, GSH, can provide significant hepaticprotection, however.