辛二酰苯胺异羟肟酸对初进高原致死性失血性休克大鼠肝损伤的影响  

Effect of suberoylanilide hydroxamic acid on liver injury induced by lethal hemorrhagic shock in rats first entering high altitude

作　　者：张彦圆[1] 耿智隆[2] 徐鹏[2] 高晓华[2] 

机构地区：[1]兰州大学第二临床医学院,730030 [2]兰州军区兰州总医院麻醉科

出　　处：《中华麻醉学杂志》2013年第4期477-480,共4页Chinese Journal of Anesthesiology

基　　金：全军“十一五”面上基金课题（06MA083）

摘　　要：目的评价辛二酰苯胺异羟肟酸（SAHA）对初进高原致死性失血性休克大鼠肝损伤的影响。方法选择健康成年雄性sD大鼠40只，体重240～280g，2～3月龄，将大鼠从海拔1520m养殖地运输至海拔3780in的实验基地，采用随机数字表法，将其分为4组（n=10）：假手术组（s组）、致死性失血性休克组（LHS组）、生理盐水组（Ns组）、SAHA组。LHS组、Ns组和SAHA组经股动脉和股静脉放血制备致死性失血性休克模型。Ns组和SAHA组失血完成后经静脉2min内分别注射0．25ml生理盐水或SAHA7．5mg／kg（0．25m1）。记录大鼠3h生存情况。于失血前、失血完成后即刻、失血完成后3h时（存活时间不足3h时则于死亡即刻）采集股静脉血样，采用比色法检测血清AST、ALT、LDH活性。失于血完成后3h或死亡即刻取肝组织，采用Westernblot法检测肝组织c—Jun氨基末端激酶（JNK）、磷酸化JNK（p-JNK）和caspase-3的表达和H3K垒乙酰化水平。结果与s组比较，LHS组、Ns组和SAHA组血清AST、ALT和LDH活性升高（P〈0．01）。与LHS组和NS组比较，SAHA组血清AST、ALT和LDH活性降低，3h生存率升高，肝组织H3K9乙酰化水平升高，caspase-3表达下调，p-JNK／JNK降低（P〈0．05或0．01）。LHS组和Ns组肝组织病理学损伤严重，SAHA组病理学损伤私度明显减轻。结论初进高原致死性失血性休克大鼠休克早期应用SAHA具有肝保护作用，其作用机制与提高肝细胞H3K9乙酰化水平，抑制JNK／caspase-3凋亡信号转导通路有关。Objective To evaluate the effect of suberoylanilide hydroxamic acid （SAHA） on liver injury induced by lethal hemorrhagic shock in rats first entering high altitude. Methods Forty healthy male Sprague- Dawley rats, aged 2-3 months, weighing 240-280 g, transported from breeding grounds at an altitude of 1520 meters to the experimental station at an altitude of 3780 meters, were randomly divided into 4 groups （ n = 10 each）： sham operation group （group S）, lethal hemorrhagic shock group （group LHS）, normal saline group （group NS）, and SAHA group. Anesthesia was induced with inhalation of 3 % isoflurane and maintained with in- halation of 0. 5 %-1.0 % isoflurane. Lethal hemorrhagic shock was induced by withdrawing blood from the femoral artery in groups LHS, NS and SAHA. Normal saline 0.25 ml and SAHA 7.5 mg/kg （0.25 ml） were injected in- travenously over 2 min after completion of blood-letting in groups NS and SAHA, respectively. The survival rates with 3 h were recorded. Blood samples from femoral veins were taken before blood-letting, immediately after com- pletion of blood-letting and at 3 h after completion of blood-letting （immediately after death if the survival time was less than 3 h） for determination of serum aspartate aminotransferase （AST）, alanine aminotransferase （ALT） andlactic dehydrogenase （LDH） activities by the colorimetric method. Liver specimens were taken at 3 h after comple- tion of blood-letting or immediately after death for examination of the pathological changes of the liver and for deter- mination of c-Jun N-terminal kinase （JNK）, phosphorylated-JNK （p-JNK） and caspase-3 expression and acetyla- tion of H3K9 in liver tissues by Western blot. Results Compared with group S, the activities of serum AST, ALT and LDH were significandy increased in the other three groups （ P 〈 0.01 ）. Compared with LHS and NS groups, the activities of serum AST, ALT and LDH were significantly decreased, the survival rate within 3 h and acetyla- tion of H3K9

关 键 词：组蛋白脱乙酰基酶类 高原病 休克 出血性 肝功能试验 

分 类 号：R[医药卫生]