促红细胞生成素对大鼠脑缺血后神经元凋亡及热休克蛋白27和血管内皮生长因子表达的影响

目的探讨促红细胞生成素对大鼠脑缺血的保护作用。方法采用线栓法阻断大鼠一侧大脑中动脉制作大鼠局灶性缺血再灌注模型。促红细胞预处理组于缺血开始前2h予腹腔注射促红细胞生成素3000u/kg;缺血再灌注组和假手术组在手术前2h予腹腔注射等量生理盐水。再灌注24h后进行细胞凋亡检测及热休克蛋白27和血管内皮生长因子免疫组织化学染色。结果再灌注24h后,缺血再灌注组可见较多的POD阳性细胞(67.48±11.17个/高倍视野),促红细胞生成素预处理组缺血区阳性细胞数目减少(45.25±4.72个/高倍视野,P<0.01),假手术组偶见个别阳性细胞,正常组未见凋亡细胞;与缺血再灌注组(25.60±4.42个/高倍视野)相比,促红细胞生成素预处理组热休克蛋白27表达增加(67.56±13.84个/高倍视野,P<0.01);促红细胞生成素预处理组血管内皮生长因子表达较缺血再灌注组亦增加(74.90±11.64个/高倍视野比40.14±7.50个/高倍视野,P<0.01))。结论促红细胞生成素预处理后可抑制缺血损伤后缺血侧皮层细胞凋亡,其机制可能是通过上调热休克蛋白27和血管内皮生长因子基因表达而实现的。

Effect of Erythropoietin on Neuronal Apoptosis and Expression of Heat Shock Protein 27 and Vascular Endothelial Growth Factor After Rat Cerebral Ischemia

Aim To investigate protection of erythropoietin(EPO)on rat cerebral ischemia.Methods The model of focal cerebral ischemia-reperfusion injury was made by occluding middle cerebral artery(MCA).At 2 hours before cerebral ischemia,EPO group received an intraperitoneal injection of rHu-EPO(3 000 u/kg),while ischemia-reperfusion group and sham operation group received same doses of saline.The brains were removed 24 hours after reperfusion.Apoptosis and expressions of heat shock protein 27(HSP27)and vascular endothelial growth factor(VEGF)were detected.Results After 24 hours of reperfusion,it was thus clear that ischemia-reperfusion group(67.48±11.17 cells/HP)had major POD masculine cells,EPO group(45.25±4.72 cells/HP)was decreased,there was significant difference between the two groups(p<0.01),no TUNEL positive cell was found in control group and sham operation group.Compared with ischemia-reperfusion group(25.60±4.42 cells/HP),the expression of HSP27 in EPO group was increased(67.56±13.84 cells/HP,p<0.01).About the expression of VEGF,there was significant difference between EPO group and ischemia-reperfusion group(74.90±11.64 cells/HP vs 40.14±7.50 cells/HP,p<0.01).Conclusion EPO pretreatment could inhibit apoptosis of cortical neurons after cerebral ischemia-reperfusion injury,partially mediated by the up-regulation of HSP27 and VEGF expression.