中脑胶质细胞神经营养因子前多肽对大鼠神经元的保护作用

目的 观察中脑胶质细胞神经营养因子(MANF)前多肽对由谷氨酸所致大鼠下丘脑神经元损伤的保护作用及量效关系.方法 将培养Wistar大鼠下丘脑神经元分为正常对照组(CG)、谷氨酸组(GG)、MANF前多肽+谷氨酸组(MGG1～4,MANF前多肽浓度分别为1×10-7、1×10-8、1×10-9、1×10-10 mol/L).各组神经元培养24 h后,分别检测培养细胞死亡率、神经元轴突长度、最长树突长度和树突数量.结果 GG组神经元死亡率为(0.342±0.055)%,显著高于CG组的(0.065±0.017)%(P＜0.01);MGG1组细胞死亡率最低(0.157±0.038)%,并随MANF浓度降低依次增高,MGG4的细胞死亡率最高,达(0.285±0.035)%,MGG1组神经元轴突长度、最长树突长度和树突数量均为最高,分别为(133.5±21.6)μm、(128.4±18.6)μm、(1.84±0.27)个/细胞,并随MANF浓度降低依次减少,MANF组细胞死亡率和神经元形态均较GG组明显改善(P＜D.05),但仍较CG组较差(P＜0.05),MANF前多肽浓度越高者,神经元情况改善越好.结论 MANF前多肽对谷氨酸所致神经元损伤有显著的保护作用,且在1×10-7～1×10-10 mol/L浓度范围内随浓度增高,保护效果增强.

Abstract：

Objective To observe the protective effects of pre-mesencephalic astrocyte-derived neurotrophic factor ( MANF) polypeptide on glutamate-induced rat hypathalamus neuron injury and the dose-effect relationship. Methods Cultured Wistar rats hypothalamic neurons were divided into normal control group (CG) , glutamate group (GG), pre-MANF polypeptide + glutamate groups (MGGM, preMANF polypeptide concentrations were 1 × 10 -7 , 1 × 10 -8, 1 × 10-9 and 1 ×10 -l0 mol/L) randomly. After culture for 24 h, mortality of neurons was tested, and length of neuron axons, the maximum length and number of dendrites were measured. Results The neuronal death rate in GG group was (0. 342 ± 0. 055 ) % , significantly higher than that in CG group (P ＜ 0. 01) . The cell mortality, neuron axon length,the maximum length and number of dendrites in MGG1 groups were (0. 157 ±0.038)% , (133. 5 ±21.6) μm, (128. 4 ± 18. 6) μm, 1. 84 ±0. 27 per cell respectively, and significantly improved as compared with GG group (P ＜ 0. 05) , but were still worse than in CG group (P ＜0. 05). Higher the pre-MANF polypeptide concentration was, better the neuron figure showed. Conclusion Pre-MANF polypeptide has a significant protective effect on neuron injury caused by glutamate, and the protective effect is stronger as the concentration higher within 1 × 10-7-1×10 -10 mol/L.