EPO的抗衰老作用及其作用机制的初步探讨

The Anti-aging Effect of EPO and the Preliminary Probe into Its Mechanisms

目的研究促红细胞生成素(EPO)是否具有抗衰老作用,并初步探讨其作用机制。方法采用皮下注射5%D-半乳糖2.5mL/(kg.d)共6周建立大鼠衰老模型。将大鼠随机分为正常对照组,衰老模型组及小〔1000U/(kg.d)〕、中〔3000U/(kg.d)〕、大剂量〔5000U/(kg.d)〕重组人促红细胞生成素(rhEPO)干预组,每组10只。Morris水迷宫实验分析比较各组间大鼠的学习记忆能力;处死小鼠后检测脑组织中丙二醛(MDA)、Na+-K+ATP酶、总抗氧化能力(T-AOC)、超氧化物歧化酶(SOD);每组随机抽取1只大鼠,观察海马组织超微结构的差异。结果①衰老模型组较正常对照组大鼠学习记忆能力下降,脑组织MDA水平升高,Na+-K+ATP酶、T-AOC及SOD活性降低(P<0.05),且海马组织超微结构呈现一系列衰老改变;②中剂量rhEPO干预组较衰老模型组大鼠学习记忆能力提高,脑组织MDA水平下降,Na+-K+ATP酶、T-AOC及SOD活性升高(P<0.05),且海马组织电镜下超微结构较之改善;③小剂量rhEPO干预可部分对抗衰老大鼠脑组织Na+-K+ATP酶及SOD活性的降低(P<0.05),对其余指标无显著影响,大剂量rhEPO干预对衰老大鼠的各项指标均无显著改善(P>0.05)。结论中剂量的EPO具有抗衰老作用,其作用机制可能与增强抗氧化酶活性、提高抗氧化能力有关。

Objective To study whether erythropoietin （EPO） has the anti-aging effect and the mechanisms of how it effects. Methods 5% D-galactose hypodermic injection for 6 weeks to establish the aging model. Divided rats into 5 groups randomly： the normal control （group A）, the aging model （group B）, the low dosage [1 000 U/ （kg · d）] of recombinant human erythropoietin （rhEPO） intervene （group C）, the middle dosage [3 000 U/（kg · d）] of rhEPO intervene （group D） and the high dosage [5 000 U/（kg · d）] of rhEPO intervene （group E）, 10 rats in each group. Morris water maze was used to comparing the behavioral indexes. After decapitating the rats, the malonaldehyde （MDA）, Na＋-K＋ ATPase, total antioxidant capacity （T-AOC） and superoxide dismutase （SOD） of brain tissue were tested, one rat from each group was selected randomly to observe the hippocampal ultramicro- structure. Results ①Compared with group A, the learning and memory ability of group B reduced, the level of MDA, the Na＋-K＋ ATPase, T-AOC and the SOD activities of brain tissue decreased （P〈0.05）, besides, a series of aging changes were observed in the hippocampal ultramicro-structure in group B. ②Compared with group B, an improved learning and memory ability of group D, a reduced MDA content and an increased activity of Na＋-K＋ ATPase, T-AOC and the SOD activities of brain tissue in group D were also observed with a improved hippocampal ultramicro-structure.③ The low dosage of rbEPO intervention could against the decrease of the activities of brain Na＋-K＋ ATPase, SOD of aging rat （P〈0.05）, but had no significant effects on the rest of the indicators, the high dosage of rhEPO intervention had no significant improvements on various indicators of aging rats in high dosage of rhEPO intervention groupwas noticed （P〉0.05）. Conclusion The middle dosage of EPO has the anti-aging effect, and its mechanisms may be related to enhancing the antioxidant enzymes activity and increasing the antioxidant capacity.