重组人促红细胞生成素对大鼠急性创伤性脑损伤脑组织中基质金属蛋白酶-9及水通道蛋白-4表达的影响

目的 探讨重组人促红细胞生成素（rhEPO）对大鼠急性创伤性脑损伤的神经保护作用及其机制。方法健康雄性SD大鼠55只随机分为假手术组（n=5）、对照组（n=25）和EPO治疗组（n=25）；对照组和治疗组采帽改进的Feeney等的方法制作脑创伤模型，EPO治疗组在模型建立后立即腹腔注射rhEPO5000U／kg，对照组和似手术组往等时间点给予等量生理盐水。根据伤后处死时间点不同每组再分为5个亚组，即6h、24h、48h、3d、7d组．每个亚组5只动物。断头、取脑，行HE染色和免疫组织化学方法检测大脑皮层组织中基质金属蛋白酶-9（MMP-9）及水通道蛋白-4（AQP-4）的表达。结果脑创伤大鼠6h创伤灶脑组织出现MMP-9和AQP-4的表达。与假手术组比较，差异有统计学意义（P〈0．05）。EPO治疗组和对照组槲比较MMP-9及AQP-4的表达明显降低（P〈0．05）。结论 rhEPO对大鼠急性创伤性脑损伤有一定的神经保护作用，其机制可能是通过降低MMP-9及AQP-4的表达来实现的。

Effects of rhEPO on expression of MMP-9 and AQP-4 in brain tissues of rats with acute traumatic brain injury

Objective To explore the neuroprotective mechanisms of recombinant humam erythropoietin(rhEPO) on the rats after acute traumatic brain injury.Methods Fifty-five healthy adult male SD rats were randomly dividied into sham operation group(n=5),control group(n=25) and the EPO treatment group(n=25).The traumatic brain injury of the latter two groups was induced by Feeney’s.rhEPO treatment group underwent intraperitoneal injection of 5000 U/kg rhEPO after the injury.The rats in the control group and the EPO treatment group were redivided into 5 subgroups(6 h、24 h、48 h、3 d、7 d groups) of 5 rats each respectively according to different time after the injury.The histology was detected by HE staining,the expression of MMP-9 and AQP4 was detected by immunohistochemical.Results The expression of MMP-9 and AQP-4 in the brain tissue of the injury appeared 6 hours after trauma and was significantly higher in the injury group than that in the sham operation group(P<0.05).The expression was significantly lower in rhEPO treatment group than that in control group(P<0.05).Conclusion Recombinant human EPO may be neuroprotective against acute traumatic brain injury in rats,probably by inhibiting the activities of MMP-9 and AQP-4.