重组人促红细胞生成素对大鼠局灶性脑缺血再灌注损伤的保护作用

目的 探讨重组人促红细胞生成素(EPO)对大鼠局灶性脑缺血再灌注损伤所致炎性反应的保护机制。方法采用线拴法制备大鼠局灶性大脑中动脉缺血再灌注模型，应用TTC染色法、干湿重法、常规HE染色法观察EPO治疗前后再灌注24h脑梗死体积、脑组织含水量以及组织学变化，应用RT- PCR方法检测EPO治疗前后再灌注lh、3h、6h、12 h、24h、72 h缺血侧脑皮质IL-1β、TNF-α基因表达的变化。结果与假手术组相比，EPO可显著缩小缺血再灌注24h所致的脑梗死体积(P＜0.01)，降低梗死侧脑组织含水量(P＜0.01)，减轻病理学变化。缺血再灌注各时相点缺血侧皮层IL -lβ mRNA和TNF -α mRNA表达均显著上调(P＜0.01)，12 h达高峰。EPO治疗后lh、3h、6h缺血侧皮层IL - 13 mRNA表达显著下降，与病理组相应时间点相比，分别降低了63％、55％和84％(P＜0.01)。EPO治疗后lh、3h、6h缺血侧皮层TNF -α mRNA表达亦显著下降，与病理组相应时间点相比，分别降低了75％、76％和95％（P＜0.01）。结论EPO可能通过抑制IL - 1β、TNF-α的基因表达，降低缺血再灌注的炎性反应损伤而改善脑组织的结构和功能。

Effects of EPO on IL - 1 and TNF gene expression induced by focal cerebral ischemia - reperfusion m rats

Objective To explore the neuroprotection of r - HuEPO (EPO) on brain injury and gene expression of inflammatory factors IL - 1β and TNF - αt in rats with focal cerebral ischemia /reperfusion. Method Thread embolism was performed to generate cerebral ischemia/reperfusion model in rats. Morphological changes in brain were observed under light microscope after routine HE staining. Cerebral infarct size was measured after stained by 2,3,5 - triphenyltetrazolium chloride ( TTC ). Water content of both hemispheres was calculated at 24 h after reperfusion. RT - PCR was employed to determine the mRNA level of IL - 1β and TNF - α in the presence and absence of EPO. Results Compared with the sham group, EPO treatment significantly reduced the infarct size ( P ＜ 0. 01 )and tissue water content( P ＜0.01). The mRNA levels of IL - 1β and TNF -αt were significantly increased ( P ＜0.01) in the ischemic cortex at every time point in I/R groups. The peak level of IL-1β and TNF-αt mRNA was expressed at 12 h ( P ＜0. Ol ). The induction of IL - 1β mRNA by I/R was significantly reduced by 63％ ,55％ ,84％ at 1,3,6 h in ischemic brain of EPO + I/R groups( P ＜0. 01 ). Similarly, mRNA expression of TNF - α induced by I/R was significantly inhibited by 75％,76％,95％ at 1,3,6 h in ischemic brain of EPO +I/R groups( P ＜0.01). Conclusions Inhibition of the gene expression of IL - 1β3 and TNF - αt mRNA may be one of the critical mechanisms for EPO to protect neural tissue injury in cerebral ischemia/reperfusion in rats.