目的 研究重组人促红细胞生成素(recombinant human erythropoietin,rhEPO)对感染性休克(septic shock,SS)大鼠脑组织的保护作用.方法 将健康雄性Vistar大鼠36只按随机数字表法分为正常对照组(n=12)、感染性休克组(n=12)、rhEPO治疗组(n=12),每组再分成2个时间点(6、12 h),各时间点6只.感染性休克组和rhEPO治疗组以尾静脉注射内毒素(LPS)5 mg·kg-1制备感染性休克模型,rhEPO治疗组在出现休克症状时立刻腹腔注射rhEPO 5 000 U·kg-1;正常对照组大鼠给予等量生理盐水.术后各组各时间点大鼠分批腹腔麻醉后行眼球摘除术采血及断头取脑组织:取血清行NSE检测、脑组织匀浆行NO检测;提取右半侧脑组织海马区进行病理切片,行HE染色和TUNEL染色检查.结果 与正常对照组比较,感染性休克组脑海马CA1区神经元损伤明显,可见大量TUNEL阳性细胞,NO、NSE含量显著升高(均P＜0.01);rhEPO治疗组TUNEL阳性细胞和NO、NSE含量较感染性休克组明显降低(P＜0.01或P＜0.05).结论 rhEPO可减轻感染性休克时脑组织损伤及海马区神经元细胞的凋亡,其机制可能与抑制NO的过量生成有关.%Objective To study the protective role of recombinant human erythropoietin (rhEPO) on brain in rats with septic shock. Methods Thirty six rats were randomly divided into threegroups: control group(n= 12), septic shock group(n = 12) and rhEPO group(n = 12). Rats in septic shock and rhEPO groups were injected intravenously with 5 mg· kg-1 endotoxin to establish the models of septic shock. In rhEPO group, rats were intraperitoneally injected with 5 000 U · kg-1 rhEPO immediately when shock signs appeared. Rats in control group were given the same volume of normal saline. The rats were intraperitoneally anesthetized and ophthalmectomy was performed at different time points (6 and 12 hours,n=6). The blood samples were taken to detect the concentration of NSE and the brain tissue was obtained to measure the concentration of nitric oxide (NO). Pathological sections of the right brain were stained with HE and TUNEL.Results Compared with the control group,septic shock obviously damaged neurons in hippocampal CA1 region and significantly increased the number of TUNEL-positive cells and the levels of NSE and NO (P＜0.01),but the changes were significantly inhibited by rhEPO(P＜0.01 or P＜0.05). Conclusion The rhEPO can reduce the brain damage and hippocampal neuron apoptosis in rats with septic shock, and the effect of rhEPO might be mediated by a mechanism involving the inhibition of excessive NO.
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