丹参酮对脊髓缺血再灌注损伤HIF1-1α和VEGF的作用及机制  

Effect and Mechanism of Tanshinone on the Expressions of HIF-1α and VEGF during Spinal Cord Ischemia-reperfusion Injury

作　　者：伏勇[1] 黄志高[1] 张俐[1] 

机构地区：[1]福建中医学院,福州350108

出　　处：《中国中医骨伤科杂志》2010年第5期5-7,12,共4页Chinese Journal of Traditional Medical Traumatology & Orthopedics

基　　金：国家自然科学基金项目(30572401);人事部留学人员科技活动项目(国人厅发[2006]164);福建省自然基金项目(2008J0094)

摘　　要：目的:从组织形态学观察丹参酮对脊髓缺血再灌注损伤的作用;探讨丹参酮对脊髓缺血再灌注损伤血管内皮生长因子和HIF-1α的作用及机制?椒?1.脊髓缺血再灌注损伤模型建立与鉴定后,将120只大鼠随机分为丹参酮组(A组)、对照组(B组)和假手术组(C组),每组40只。造模成功后,A组术前30min腹腔注射丹参酮注射液,B组术前30min腹腔注射等量的生理盐水,C组,麻醉和手术操作同上,不阻断腹主动脉即终止手术,逐层缝合。室温下自然苏醒。上述大鼠缺血30min后分为再灌注0.5h、1h、4h、8h、12h,共5个时间点,每组每个时间点8只。取各组大鼠的脊髓组织,随机抽取大鼠2只,切取脊髓标本。制备成光学显微镜观察标本,运用光镜观察各组脊髓组织病理改变。2.采用RT-PCR检测脊髓组织中VEGFmRNA和HIF-1α的表达?峁?1.脊髓组织病理改变显示:丹参酮组神经细胞肿胀程度、核仁萎缩程度等均损害表现较对照组轻。2.脊髓缺血再灌注损伤0.5～4h,3组之间VEGFmRNA表达比较差异无统计学意义,脊髓缺血损伤8～12h,VEGFmRNA表达呈时间依赖性升高,8h和12h,丹参酮与对照组相比差异有统计学意义(P<0.05)。3.对照组和丹参酮组,脊髓缺血再灌注损伤0.5～1h,HIF-1αmRNA表达呈时间依赖性下降,丹参酮组明显低于对照组,差异有统计学意义,随后不再下降。结论:丹参酮注射液可能通过促进血管内皮生长因子表达,减少HIF-1α的表达,改善脊髓缺血再灌注损伤组织局部缺氧环境,对减轻脊髓缺血再灌注损伤起到积极的防治作用。Objective：To investigate the histomorphological influence of Tanshinone on spinal cord ischemia-reperfusion injury,and to explore its effect and mechanism on the expressions of vascular endothelial growth factor（VEGF）and hypoxia inducible factor（HIF）-1α.Methods：After the animal model of spinal cord ischemia-reperfusion injury was successfully established,120 rats were randomized into Tanshinone group,control group,and sham operation group,40 in each.Thirty minutes before the operation,intraperitoneal injection of Tanshinone and normal saline was respectively given to Tanshinone group and control group.While in sham operation group,the anesthesia and operation were the same as in the above two groups,but the abdominal aorta was not blocked.There were totally 5 time points as 0.5h,1h,4h,8h and 12h after spinal cord injury,8 rats for each time point.Microscope was used to observe histopathologic changes,and reverse transcription-polymerase chain reaction（RT-PCR）was used to detect the mRNA expressions of VEGF and HIF-1α in spinal cord tissues.Results：The degrees of cellular swelling and nucleolus atrophia of nerve cells were relatively lower in Tanshinone group than in control group.During 0.5h to 4h after spinal cord injury,there was no significant difference between the three groups in VEGF mRNA expression.However,from 8h to 12h,VEGF mRNA expression showed a time-dependent manner,and there was remarkable difference between Tanshinone group and the control.From 0.5h to 1h,HIF-1α mRNA expression decreased time-dependently,with the level in Tanshinone group apparently lower than in control group,and then stopped decreasing.Conclusion：This study shows that Tanshinone might protect spinal cord in ischemia-reperfusion injury via promoting VEGF expression while inhibiting HIF-1α expression,thus improve the local hypoxic conditions of the injured spinal cord.

关 键 词：丹参酮ⅡA 脊髓缺血再灌注 缺氧诱导因子-1Α 血管内皮生长因子 

分 类 号：R285.5[医药卫生—中药学]