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目的观察促红细胞生成素(EPO)对帕金森病(PD)模型大鼠的保护作用并探讨其机制。方法实验大鼠分为3组,1 PD组:6-羟基多巴(6-OHDA)定向注射至右侧前脑内侧束建立PD模型;2 EPO组:在模型制备前持续1周给予腹腔注射EPO 10 000 U·kg-1·d-1;3假手术组:大鼠脑内立体定向注射生理盐水。采用ELISA法检测大鼠脑脊液EPO含量变化,术后3周评估大鼠行为学改变,免疫组化学、免疫荧光及蛋白印迹法分别检测酪氨酸羟化酶(TH)、EPO受体(EPO-R)及丝氨酸/苏氨酸激酶(Akt)磷酸化(Ser473)的表达。结果 1 EPO组脑脊液内EPO含量[(416.59±9.34)μU·L-1]增加,与假手术组[(2.20±1.92)μU·L-1]比较,差异有统计学意义(P<0.05);2 EPO组的行为学改善,黑质多巴胺能神经元的丢失减少,黑质EPO-R的表达增加,与PD组及假手术组比较,差异有统计学意义(P<0.05);3 EPO组黑质Akt磷酸化(Ser473)的表达明显增加,与PD组及假手术组比较,差异有统计学意义(P<0.05)。结论 EPO腹腔注射可以改善PD大鼠的运动症状,与EPO增加PD大鼠的磷酸化Akt(Ser473)表达可能有关。
Objective To investigate the protective effect of erythropoietin (EPO) on Parkinson’s disease (PD) model rats and its mechanism. Methods The experimental rats were divided into 3 groups, 1 PD group: 6-hydroxydopamine (6-OHDA) directed injection to the right forebrain lateral PD model; 2 EPO group: EPO 10 000 U · kg-1 · d-1; 3 Sham-operated group: Rats were stereotactically injected with normal saline. The levels of EPO in rat cerebrospinal fluid (CSF) were measured by ELISA. Behavioral changes were evaluated 3 weeks after operation. Immunohistochemistry, immunofluorescence and Western blotting were used to detect the levels of tyrosine hydroxylase (TH), EPO- R) and serine / threonine kinase (Akt) phosphorylation (Ser473). Results Compared with the sham operation group [(2.20 ± 1.92) μU · L-1], the EPO content in the CSF of 1 EPO group increased (416.59 ± 9.34 μU · L -1) (P 0.05) (P <0.05); 2 EPO group behavior improved, loss of nigral dopaminergic neurons decreased, substantia nigra EPO-R expression increased, compared with PD group and sham operation group, the difference was statistically significant (P <0.05); 3 EPO The expression of Akt phosphorylation (Ser473) in substantia nigra significantly increased compared with PD group and sham operation group, the difference was statistically significant (P <0.05). Conclusion Intraperitoneal injection of EPO can improve motor symptoms in PD rats, which may be related to the increase of phosphorylated Akt (Ser473) expression in PD rats induced by EPO.