局灶性脑缺血再灌注损伤模型大鼠与促红细胞生成素的神经保护作用

Neuroprotective effect of erythropoietin in a rat model of cerebral ischemia-reperfusion models

背景:近年来动物实验和体外细胞培养研究证实促红细胞生成素对脑缺血具有神经保护作用,有关促红细胞生成素脑保护的作用机制目前尚未阐明。目的:通过观察缺血损伤区域脑组织细胞学形态,检测脑组织超氧化物歧化酶、丙二醛浓度,探讨促红细胞生成素对脑缺血再灌注损伤的保护作用。方法:采用线栓法建立Wistar大鼠局灶性缺血再灌注损伤模型,分别于缺血后2h腹腔注射生理盐水3000U/kg、促红细胞生成素3000,1000U/kg,并设假手术组。缺血再灌注损伤24h后,应用苏木精-伊红染色法检测大鼠脑组织病理学变化,应用黄嘌呤氧化酶法和硫代巴比妥酸法分别测定超氧化物歧化酶活性和丙二醛浓度。结果与结论:形态学结果显示促红细胞生成素高剂量组较生理盐水组皮质神经细胞存活数量增多,损伤程度减轻;促红细胞生成素高、低剂量组超氧化物歧化酶活性均明显高于假手术组和生理盐水组(P<0.05),丙二醛浓度明显低于假手术组和生理盐水组(P<0.05);促红细胞生成素高剂量组超氧化物歧化酶活性明显高于促红细胞生成素低剂量组,丙二醛含量明显低于促红细胞生成素低剂量组(P<0.05)。提示经腹腔注射促红细胞生成素,可使大鼠脑缺血再灌注损伤区神经细胞存活数量明显增加,可显著改善组织的病理学改变,其保护作用可能是通过促红细胞生成素清除自由基,拮抗过氧化损伤实现的。

BACKGROUND： In recent years, animal experiments and in vitro cell culture studies confirmed that erythropoietin （EPO） has neuroprotective effect on cerebral ischemia, but the mechanism is not yet clearly. OBJECTIVE： To explore the neuroprotective effect of EPO on cerebral ischemia via observing cytologic morphology at damaged area and detecting concentrations of superoxide dismutase （SOD） and malondialdehyde （MDA） in brain tissues. METHODS： Wistar rats were prepared for focal ischemia-reperfusion models by suture method. At 2 hours after model preparation, 3 000 U/kg normal saline and 1000 U/kg EPO were peritoneally injected into rats. At the same time, a sham-surgery group was established. Pathological changes of brain tissues were detected by hematoxylin-eosin staining, the SOD activity and MDA concentration were measured by xanthine oxidase and thiobarbituric acid methods at 24 hours after ischemia-reperfusion injury. RESULTS AND CONCLUSION： The morphological results demonstrated that, compared with the normal saline group, the survival of cortical nerve cells were greater in the high-dose EPO group with lighter damage. The SOD activity in the high-dose EPO, low-dose EPO groups was obviously greater than that in the sham-surgery and normal saline groups （P 0.05）, but the MAD concentration was smaller in the high-dose EPO and low-dose EPO groups （P 0.05）. The SOD activity was significantly higher in the high-dose EPO group than the low-dose EPO group, but the MAD were significantly lower than the low-dose EPO group （P 0.05）. The intraperitoneal injection of EPO can increase the survival number of nerve cells, significantly improve the pathological changes of tissues, this protective effect may be achieved via removing free radicals and antagonizing oxidative damage.