七氟醚后处理对大鼠脑缺血-再灌注损伤海马血红素氧合酶-1蛋白表达的影响

Effects of sevoflurane postconditioning on heme oxygenase-1 expression in hippocampal against cerebral ischemia-reperfusion injury

目的探讨七氟醚后处理对大鼠脑缺血-再灌注损伤的保护作用及血红素氧合酶-1(HO-1)在其中的作用。方法清洁级雄性SD大鼠40只,体重230～270g,随机均分为五组:假手术组(C组),缺血-再灌注组(IR组),七氟醚组(S组),七氟醚+锌原卟啉IX(Znpp)组(SZ组)和溶剂对照组(SD组)。采用双侧颈总动脉夹闭合并取血降压再回输的方法制备脑缺血-再灌注损伤模型,S组再灌注前5min气管插管,吸入1MAC七氟醚15min;SZ组模型制备前腹腔注射Znpp45μmol/kg,溶于二甲基亚砜(DMSO)0.5ml;SD组模型制备前腹腔注射DMSO0.5ml。所有大鼠再灌注24h后处死,取海马。光镜下观察各组海马病理学变化,检测海马超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量和HO-1蛋白表达。结果与C组比较,其余四组SOD活性明显降低(P<0.05),MDA含量明显升高(P<0.05),SZ组HO-1蛋白表达差异无统计学意义,IR、S和SD组HO-1蛋白表达明显升高(P<0.05)。与IR组比较,S组和SD组SOD活性和HO-1蛋白表达明显升高(P<0.05),MDA含量明显降低(P<0.05),SZ组HO-1蛋白表达明显降低(P<0.05)。光镜下S组和SD组海马病理学损伤较IR组和SZ组减轻。结论七氟醚后处理对大鼠脑缺血-再灌注损伤有保护作用,其作用机制可能与七氟醚上调脑组织中HO-1蛋白表达有关。

Objective To investigate the effect of sevoflurane postconditioning on heme oxygenaseq（HO-1） expression against cerebral ischemia-reperfusion injury. Methods Forty male SD rats of clean grade weighing 230-270 g were randomly divided into 5 groups： sham operation group （group C）, cerebral IR group （group IR）, sevoflurane postconditioning group （group S）, sevo＋ Znpp （group SZ） and vehicle group（group SD）. An cerebral IR model was established by drawing blood from right carotid vein and immediate 20 min occlusion of bilateral carotid artery. Rats in group S were intubated at 5 minutes before reperfusion, and inhaled 1 MAC sevoflurane for 15 minutes. Rats in group SZ received intraperitoneal injection of Znpp 45μmol/kg in 0.5 ml DMSO before model established. Rats in group SD received the same volume vehicle and sevoflurane posteonditioning. After 24-hour reperfusion, all rats were euthanized and the hippocampus were obtained for pathological observation by light microscopy and determination of SOD activity, MDA and HO-1 content.. Results Compared with group C, SOD activities decreased and MDA contents increased significantly in other four groups （P〈0.05）. There was no significant difference in HOq expression between groups C and SZ, while HO-1 expression significantly increased in the other three groups （P d0.05）. Compared with group IR, SOD activity and HO-1 expression significantly increased and MDA content significantly decreased in groups S and SD （P〈 0. 05）. There was no significant difference in SOD and MDA between group IR and SZ, while HO-1 was significantly lower in group SZ than that in group IR （P〈0.05）. There was no significant difference in SOD, MDA and HO-1 content between group S and SD. The pathological damage of hippocampal in groups S and SD was greatly relieved in groups S and SD. Conclusion Sevoflurane postconditioning has a protective effect on rat hippocampal against cerebral ischemia-reperfusion, which might be associated with upregulation of cerebral HO-1 expresion.