Survivin在PC12细胞对抗化学性缺氧损伤中的作用  

Role of survivin in PC12 cells against injuries induced by chemical hypoxia

作　　者：孟金兰[1,2] 董艳芬[1] 莫利求[3] 杨春涛[2] 兰爱平[2] 杨战利[2] 陈培熹[2] 冯鉴强[2,3] 

机构地区：[1]广东药学院生理学教研室,广东广州510006 [2]中山大学中山医学院生理学教研室,广东广州510080 [3]中山大学附属第一医院黄埔院区麻醉科,广东广州510080

出　　处：《中国药理学通报》2010年第4期526-530,共5页Chinese Pharmacological Bulletin

基　　金：广东省科技计划资助项目(No2008B080703053;2007B080701030)

摘　　要：目的探讨存活素(survivin)在PC12细胞对抗氯化钴(CoCl2)诱导损伤中的作用。方法应用不同浓度的CoCl2处理PC12细胞不同时间,建立化学性缺氧诱导PC12细胞损伤的实验模型。应用CCK-8比色法检测细胞存活率;Western-blot法检测CoCl2诱导缺氧与survivin表达间的量效(200～1000μmol·L-1)和时效(0～48h)关系。结果CoCl2可明显抑制PC12细胞的存活率,且呈浓度和时间依赖性。应用不同浓度CoCl2处理PC12细胞24h,在200～600μmol·L-1浓度范围内,呈浓度依赖性地促进survivin表达,600μmol·L-1CoCl2诱导survivin表达达高峰,超过此浓度,则随着CoCl2浓度的增加,survivin表达逐渐下降,CoCl2浓度达1000μmol·L-1时,survivin基本不表达;应用600μmol·L-1CoCl2处理PC12细胞,在0～36h时间范围内,呈时间依赖性地促进PC12细胞survivin的表达,但随着处理时间的延长,survivin的表达逐渐下降;加入2μmol·L-1Hsp90抑制剂17-丙烯胺基-17-去甲氧基格尔德霉素(17-AAG),不仅可以降低600μmol·L-1 CoCl2诱导的survivin高表达,而且加重了600μmol·L-1 CoCl2对PC12细胞的损伤作用,使细胞存活率降低。结论survivin表达上调可能是PC12细胞对抗化学性缺氧损伤的内在防御机制之一。Aim To explore the effect of survivin in PC12 cells against injuries induced by cobalt chloride（CoCl2）.Methods PC12 cells were exposed to CoCl2 at different doses in different time to set up the chemical hypoxia induced PC12 cells injuries model.Cell viability was tested by using cell counter kit-8.Dose-effect（200-1 000 μmol·L^-1）and time-effect（0~48 h）relationship between hypoxia induced by CoCl2 and the expression of survivin was evaluated by western blot.Results PC12 cells viability was inhibited significantly by CoCl2 in a dose and time dependent manners;At the concentrations from 200 to 600 μmol·L^-1 CoCl2 for 24 h,survivin expression was upregulated in a dose dependent manner,peaking at 600 μmol·L^-1 CoCl2 treatment,exceeding this concentration of CoCl2,with dose increasing,survivin expression decreased.At the dose of CoCl2 up to 1 000 μmol ·L^-1,survivin did not express basically;Treatment with 600 μmol·L^-1 CoCl2 in different time,within the range of 0~36 h,the expression of survivin enhanced in time dependent manner.But with the extension of time,survivin expression was declining; 17-allylamino-17-demethoxygeldanamycin （2 μmol·L^-1）,an inhibitor of Hsp90,not only decreased survivin overexpression but also obviously enhanced the injuries of PC12 cells induced by CoCl2,which didn＇t damage PC12 cells alone.Conclusion Upregulation of survivin expression may be one of the endogenous defense mechanisms for PC12 cells against chemical hypoxia.

关 键 词：氯化钴 化学性缺氧 存活素 热休克蛋白90 PC12细胞 17-丙烯胺基-17-去甲氧基格尔德霉素 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学] R329.25[医药卫生—基础医学]