rHuEPO对大鼠脑出血病理变化及神经细胞凋亡的影响

rHuEPO attenuates neuropathology and restrains apoptosis in rats with intracerebral hemorrhage

目的观察重组人促红细胞生成素(rHuEPO)对大鼠脑出血不同时期病理变化及神经细胞凋亡的影响,探讨rHuEPO对出血性脑损伤的脑保护作用及其作用机制。方法Wistar雄性大鼠随机分为正常组(N)、假手术组(S)、模型组(M)、低剂量rHuEPO治疗组(LR)、高剂量rHuEPO治疗组(HR)。VII型胶原酶注射法制备脑出血模型,观察治疗前后脑组织含水量及脑出血量变化,采用免疫组织化学方法检测脑组织Bcl-2、Bax表达,TUNEL法检测凋亡细胞。结果与M组比较,LR组及HR组脑组织含水量降低,出血量及凋亡细胞数减少,Bcl-2蛋白表达升高,Bax蛋白表达下降,尤以HR组为著。结论rHuEPO可通过介导Bcl-2表达上调及Bax表达下调抑制细胞凋亡,同时可减轻脑水肿,促进血肿吸收,其上述作用与剂量呈正相关。

Objective To observe the effects of rHuEPO on the changes of neuropathology and apoptosis in rats with intracerebral hemorrhage and study the neuroprotection mechanism of rHuEPO for intracerebral hemorrhage. Methods Male Wistar rats were randomly divided into five groups ： Normal group （ N ）, sham-operated group （ S ）, Model group （ M ）, Low-dose rHuEPO treatment group （LR） and High-dose rHuEPO treatment group （HR）. The intracerebral hemorrhage （ICH） rat model was established by intracranial injection of Ⅷ collagenase. Brain edema were assayed by dry/wet weight method. The expression of Bax and Bcl-2 were analyzed by immunohistochemistry and apoptosis was measured with TUNEL. Results The brain water content,volume of hematoma,number of apoptosis cell and Bax in perihematoma in LR group and HR group were downregulated and Bcl-2 were upregulated as compared with M group. The above roles of rHuEPO were more significant in HR group. Conclusion rHuEPO could suppress apoptosis by upregnlation of Bcl-2 and downregulation of Bax,lessening the cerebral edema and enhancing the absorption of hematoma. There is a dose-effect relationship between different rHuEPO dose groups.