摘要
目的探讨二氮嗪(DE)进行药物预处理能否模拟缺血预处理(IPC)对肝脏缺血再灌注损伤的延迟保护作用及其可能的作用机制。方法建立大鼠70%肝脏热缺血再灌注(IR)损伤模型。实验共分为5组IPC组以肝缺血5min作预处理;DE组以静脉注射DE作为预处理;DE+5-HD组是在DE组基础上再予静脉注射线粒体ATP敏感性钾通道(mitoKATP通道)选择性阻滞剂5-HD进行预处理;对照组(C组)以静脉注射等量生理盐水作为预处理;上述4组均在预处理24h后行肝缺血1h再灌注3h;假手术组(S组)仅行二次开腹手术,不作处理。在完成预定实验操作后分别取下腔静脉血进行肝血清酶(ALT、LDH)检测,取肝组织进行超氧化物歧化酶(SOD)活力与丙二醛(MDA)含量及肝组织湿重干重(WD)的测定,并行肝组织的显微结构观察。结果C组ALT、LDH、MDA及WD的水平明显高于S组(P<0.01),而SOD活性明显低于S组(P<0.01),肝脏在光镜下的显微结构损伤明显;IPC组与DE组的各项肝组织损伤指标均明显好于C组(P<0.05及P<0.01);而DE+5-HD组的肝损伤指标均差于DE组(P<0.05及P<0.01)。结论使用DE进行药物预处理能够模拟出IPC效应,对大鼠肝脏IR损伤具有延迟保护作用,其发生机制可能与诱导肝脏SOD活性增加、提高肝脏的抗氧化能力,以及改善肝组织微循环、减轻肝脏水肿有关。
Objective To determine the likelihood of Diazoxide (DE), a selective opener of mitochondrial ATP-sensitive potassium (mitoK_~ATP ) channels, mimicking the delayed protective effect of ischemic preconditioning (IPC) on liver ischemia/reperfusion(I/R) injury. Methods Four groups of SD rats(n=8 each) were pretreated with: 5-min period of liver ischemia (IPC group), DE 5 mg/kg iv (DE group), DE plus 5-HD, a selective mitoK_~ATP inhibitor 5-hydroxydecanoate(DE+5-HD group), and with saline(control group). Twenty-four hours later, the pretreated rats were subjected to 60 min sustained liver ischemia followed by 180 min reperfusion to form the model of 70% liver warm I/R injury. An additional fifth group of rats was set, in which only anesthesia and laparotomy was performed twice, without pretreatment or liver I/R (sham group). Finally, blood and liver samples were obtained to determine the biochemistry and pathology of the liver. Results In the control group, the values of ALT, LDH, MDA and W/D were significantly increased, that of SOD was decreased, and there were severe hepatic tissue damages, compared with the results in sham group(P<0.01). In both IPC and DE groups, the I/R injuries were ameliated as indicated by the changes in the above parameters(P<0.05). Of course, in the DE+5-HD group, where the protection was abolished as expected, the parameters were relatively poor, as compared to those in DE group(P<0.05). Conclusion DE can mimic the delayed protective effects of IPC, possibly due to increased activity of SOD, reduced degree of hepatic tissue edema, and improved liver microcirculation.
出处
《徐州医学院学报》
CAS
2005年第3期227-230,共4页
Acta Academiae Medicinae Xuzhou
基金
江苏省卫生厅基金资助课题(Z9906)
