中文摘要：

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（1Ixmol／L）、MPEP（10Ixmol／L）和MPEP（100μmol／L）组。应用MTr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p38MAPKs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G：／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，p38MAPKs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。

英文摘要：

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.