mGluR5拮抗剂MPEP抑制大鼠NPCs增殖  

The mGluR5 antagonist MPEP inhibits proliferation of rat neural precursor cells

作　　者：赵雪超[1,2] 韩佳[2] 郭波[2] 童东东 王晓霏[2] 赵凌宇[2] 

机构地区：[1]西安市北方医院康复科,西安710043 [2]西安交通大学医学院医学遗传学与分子生物学系

出　　处：《山西医科大学学报》2014年第4期261-266,共6页Journal of Shanxi Medical University

基　　金：国家自然科学基金资助项目(81070998)

摘　　要：目的研究代谢型谷氨酸受体5(mGluR5)拮抗剂2-甲基-6-(苯乙炔)吡啶盐酸盐(MPEP)对大鼠胚胎皮质NPCs增殖的影响以及其分子机制。方法大鼠胚胎皮质NPCs分为4组:正常对照组、MPEP(1μmol/L)、MPEP(10μmol/L)和MPEP(100μmol/L)组。应用MTT比色法和神经球直径测量分析MPEP对大鼠胚胎皮质NPCs增殖的影响;采用流式细胞仪分析对细胞周期和细胞凋亡的影响;免疫蛋白印迹法观察磷酸化ERK,JNK和p38 MAPKs表达变化。结果 mGluR5拮抗剂MPEP抑制大鼠胚胎皮质NPCs增殖;与对照组相比MPEP处理组S期与G2/M期细胞数量显著减少(P<0.01),G1/G0期细胞数量显著增加(P<0.01);MPEP组早期凋亡和晚期凋亡细胞显著增加(P<0.01);与对照组相比,MPEP组ERK1/2和JNK2的磷酸化表达显著下调,p38 MAPKs的磷酸化表达显著上调。结论 mGluR5拮抗剂MPEP通过抑制ERK和JNK的磷酸化激活抑制大鼠胚胎皮质NPCs增殖。Objective To explore the effects of mGluR5 antagonist MPEP on the proliferation of rat embryonic cortical neural precursor cells（NPCs） and its molecular mechanism. Methods The rat embryonic cortical neural precursor cells were divided into four groups：normal control group, 1 μmol/L MPEP group, 10 μmol/L MPEP group, and 100 μmol/L MPEP group. MTT assay and measure- ment of neurosphere diameters were used to analyze the effects of antagonist MPEP on the proliferation of rat embryonic cortical NPCs. The effects of mGluR5 antagonist MPEP on the cell cycle and apoptosis of rat NPCs were analyzed with flow cytometer. The expression of phosphorylated ERK,JNK and p38 was examined in rat NPCs by Western blot after mGluR5 antagonist MPEP treatment. Results The mGluR5 antagonist MPEP inhibited the proliferation of rat embryonic cortical NPCs. Cell cycle analysis showed the cell percentages of S and G2/M phase were significantly decreased by mGluR5 antagonist MPEP（ P 〈 0. 01 ）. The mGluR5 antagonist MPEP significantly increased the early and late apoptosis of rat NPCs（P 〈 0.01 ）. Compared with control group,the p-ERK1/2 and p-JNK2 levels signifi- cantly decreased in MPEP groups,but p-p38 significantly increased（P 〈 0.01 ）. Conclusion mGluR5 antagonist MPEP could inhibit proliferation of rat embryonic cortical NPCs through suppressing activation of mitogen-activated protein kinases signaling pathway.

关 键 词：MGLUR5 MPEP 神经祖细胞 细胞周期 细胞凋亡 ERK1 2 JNK2 

分 类 号：Q343[生物学—遗传学]