乌司他丁对缺血性损伤兔海马HIF-1α表达的影响  

Effect of ulinastatin on hypoxia inducible factor-1α expression of hippocampal neurons in rabbits with ischemic injury

作　　者：刘冰冰[1] 张超城 周代伟[1] 刘燕君[1] 舒海华[1] 李娜[1] 肖晓山[1] 

机构地区：[1]广东省第二人民医院麻醉科,广东广州510317

出　　处：《广东医学》2017年第2期182-185,共4页Guangdong Medical Journal

基　　金：广东省中医药局建设中医药强省科研课题(编号:20141010);广东省第二人民医院青年科研项目(编号:YQ2015-009)

摘　　要：目的探讨乌司他丁(UTI)对控制性降压(CH)诱导的缺血缺氧性损伤的兔海马CA1神经元缺氧诱导因子-1α(HIF-1α)表达的影响。方法 36只健康雄性新西兰白兔随机分成假手术对照组(Cont组)、控制性降压组(CH组)和UTI预处理组(UTI+CH组),每组12只。构建硝普钠CH模型,CH组和UTI+CH组平均动脉压(MAP)均降至基础值的50%,UTI+CH组在降压前30 min静脉注射UTI 50 000 U/kg。Western blot检测HIF-1α、Bcl-2和Bax蛋白的表达水平,TUNEL染色观察海马CA1细胞凋亡,HIF-1α免疫组化染色观察CA1神经元损伤状况。结果 UTI+CH组HIF-1α和Bax蛋白表达水平明显低于CH组(P<0.05),而其Bcl-2的表达则明显比CH组高(P<0.05)。TUNEL染色的细胞凋亡指数CH组明显高于Cont组(P<0.05),而UTI+CH组则比CH组低(P<0.05)。结论 UTI可能通过抑制HIF-1α蛋白和促凋亡蛋白Bax的表达,上调抗凋亡蛋白Bcl-2的表达,从而减轻CH诱导的兔海马缺血缺氧性损伤。Objective To investigate the effects of ulinastatin on hypoxia inducible factor-1（ HIF-1α） expression of hippocampal CA1 neurons suffering from hypoxic-ischemic injury induced by controlled hypotension（ CH） in rabbits.Methods Thirty-six healthy male New Zealand white rabbits were randomly divided into sham operation group（ Group Cont）,controlled hypotension group（ Group CH） and UTI pretreatment group（ Group UTI ＋ CH）.The model of controlled hypotension was constructed by sodium nitroprusside.Ulinastatin（ 50 000 U/kg） was intravenously injected 30 min before the beginning of controlled hypotension in Group UTI ＋ CH.Western blot was applied to detect the expression of HIF-1α,Bcl-2 and Bax.The hippocampal CA1 neuron injury was observed using TUNEL staining and HIF-1α immunohistochemical staining.Results HIF-1α and Bax protein expression of Group UTI ＋ CH were significanlty lower than that of Group CH（ P〈0.05）,but Bcl-2 expression was significantly higher（ P〈0.05）.Apoptotic index of TUNEL staining was significantly higher in Group CH than in Group Cont（ P〈0.05）,but it was significanlty lower in Group UTI ＋ CH than in Group CH（ P〈0.05）.Conclusion Ulinastatin maybe suppress the expression of HIF-1α and proapoptotic protein Bax,and upregulate the expression of anti-apoptotic protein Bcl-2,so as to attenuate hypoxic-ischemic hippocampal injury induced by controlled hypotension.

关 键 词：控制性降压 缺血缺氧性脑损伤 乌司他丁 低氧诱导因子-1Α Bcl-2 Bax 

分 类 号：R734.2[医药卫生—肿瘤]