摘要
目的探讨缺氧诱导因子-1α(HIF-lα)及其靶基因促红细胞生成素(EPO)在脑缺血预处理诱导的大鼠脑缺血耐受机制中的作用。方法将84只Wistar大鼠随机分成假手术对照组(SS+SS,4只)、假手术+再缺血组(SS+MCAO,40只)、预缺血+再缺血组(IP+MCAO,40只),后两组再随机分成5个亚组。线栓法阻塞大脑中动脉建立局灶性缺血预处理模型(预缺血10min),分别在预缺血后1d、3d、7d、14d、21d进行再次缺血2h再灌注22h,然后取脑组织进行脑梗死体积测量和病理观察,免疫组化方法检测HIF-lα与EPO蛋白的表达。结果⑴IP+MCAO组中1d、3d、7d亚组的梗死体积与SS+MCAO各对应亚组相比明显减小;⑵IP+MCAO组1d、3d、7d亚组中HIF-lα蛋白表达与SS+MCAO各对应亚组相比明显增高;IP+MCAO组3d、7d亚组中EPO蛋白表达与SS+MCAO各对应亚组相比明显增高。结论缺血预处理诱导了脑缺血耐受,预缺血诱导的内源性HIF-lα及EPO蛋白表达增加参与脑缺血耐受形成的机制。
Objective To investigate the expression of hypoxia inducible factor-1α(HIF-lα) and its target gene erythropoietin(EPO)in the rat model of brain ischemic tolerance induced by ischemic preconditioning(IP). Methods Eighty-four healthy Wistar rats were enrolled randomly into three groups for different pretreatments, the sham surgery group(SS+SS,n=4), the sham and middle cerebral artery occlusion(MCAO) group(SS+MCAO, n=40) and the IP and MCAO group(IP+MCAO, n=40). The latter two groups were further divided into five subgroups due to different IP. The rats were given MCAO for 10 minutes for IP. At 1, 3, 7, 14 and 21d after IP, the rats were given the second MCAO(or sham surgery) for 2 hours followed by 22 hours reperfusion. The infarct volume was measured by triphenyl tetrazolinm chloride(TTC) staining and we detected the protein of HIF-1α and EPO by immunohistochemistry. Results ⑴The infarct volumes in the 1 d, 3 d and 7 d subgroups of IP+MCAO were significantly smaller than those of the SS+MCAO subgroups(P<0.05). ⑵The expressions of HIF-1α protein in the 1 d, 3 d and 7 d subgroups of IP+MCAO were significantly higher than those of the SS+MCAO subgroups(P<0.05), while the expressions of EPO protein in the 3 d and 7 d subgroups of IP+MCAO were significantly higher than those of the SS+MCAO subgroups(P<0.05). Conclusion Ischemic preconditioning for 10 minutes induces relative tolerance to subsequent MCAO as evidenced by reduction of infarct volumes. Endogenously produced HIF-lα and EPO may be essential mediators of cerebral ischemic tolerance.
出处
《中国卒中杂志》
2007年第2期102-107,共6页
Chinese Journal of Stroke
关键词
缺氧诱导因子
促红细胞生成素
缺血耐受
缺血预处理
脑缺血
大鼠
Hypoxia inducible factor
Erythropoietin
Ischemic tolerance
Ischemic preconditioning
Cerebral ischemia
Rat
