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

Abstract: Objective To investigate the expression of hypoxia inducible factor-1α（HIF-lα） and its targetgene erythropoietin（EPO）in the rat model of brain ischemic tolerance induced by ischemicpreconditioning(IP).Methods Eighty-four healthy Wistar rats were enrolled randomly into three groups for differentpretreatments, the sham surgery group(SS+SS,n=4), the sham and middle cerebral arteryocclusion(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 weregiven MCAO for 10 minutes for IP. At 1, 3, 7, 14 and 21d after IP, the rats were given the secondMCAO(or sham surgery) for 2 hours followed by 22 hours reperfusion. The infarct volume wasmeasured by triphenyl tetrazolinm chloride(TTC) staining and we detected the protein of HIF-1αand EPO by immunohistochemistry.Results ⑴The infarct volumes in the 1 d, 3 d and 7 d subgroups of IP+MCAO were significantlysmaller than those of the SS+MCAO subgroups(P ＜0.05). ⑵The expressions of HIF-1α protein inthe 1 d, 3 d and 7 d subgroups of IP+MCAO were significantly higher than those of the SS+MCAOsubgroups(P ＜0.05), while the expressions of EPO protein in the 3 d and 7 d subgroups ofIP+MCAO were significantly higher than those of the SS+MCAO subgroups(P ＜0.05).Conclusion Ischemic preconditioning for 10 minutes induces relative tolerance to subsequentMCAO as evidenced by reduction of infarct volumes. Endogenously produced HIF-lα and EPOmay be essential mediators of cerebral ischemic tolerance.

Key words: Hypoxia inducible factor; Erythropoietin; Ischemic tolerance; Ischemicpreconditioning; Cerebral ischemia; Rat