代谢型谷氨酸受体5对创伤性神经元损伤保护作用研究  

Protection of mGluR5 agonists against traumatic neuronal injury

作　　者：霍恺[1] 费舟[1] 刘藻斌[1] 陈涛[1] 罗鹏[1] 张磊[1] 赵明明[1] 朱杰[1] 张弛[1] 屈延[1] 姬西团[1] 

机构地区：[1]第四军医大学西京医院神经外科,陕西西安710032

出　　处：《中华神经外科疾病研究杂志》2013年第1期20-24,共5页Chinese Journal of Neurosurgical Disease Research

基　　金：国家自然科学基金资助项目(30930093)

摘　　要：目的研究代谢型谷氨酸受体5(mGluR5)的特异性激动剂对创伤性脑损伤后神经元的保护作用,并初步探讨其作用机制。方法原代培养2 w大鼠皮层神经元细胞,采用神经元机械性损伤模型,加入两种mGluR5特异性激动剂2-氯-5羟苯基甘氨酸(CHPG)和3-氰-氮苯甲酰胺(CDPPB),通过乳酸脱氢酶(LDH)释放率、caspase-3活性检测,研究mGluR5激动剂对神经元损伤可能具有的保护作用;通过western-blot检测细胞外信号调节激酶(ERK)、c-Jun氨基末端激酶(JNK)、p38表达变化并研究这种保护作用的产生机制。结果损伤后LDH释放率和caspase-3活性显著增加,CHPG和CDPPB明显抑制了LDH的释放率和caspase-3的活性,并呈剂量依赖性;Western blot结果提示,CHPG和CDPPB显著增加了ERK的磷酸化水平,而对JNK、p38无影响。结论 mGluR5的激动剂CHPG和CDPPB对机械性神经元损伤具有保护作用,这种保护作用可能是通过激活ERK通路实现。Objective To investigate the neuroprotection of specific metabotropic glutamate receptor 5 （mGluRS） specific agonist on traumatic brain injury and its mechanism. Methods Cortical neurons were cultured for 2 w. Lactate dehydrogenase （LDH） and caspase-3 activity assay were used to examine the neuroprotectoon of two mGluR5 specific agonists including （ R, S ）-2-chloro-5-hydroxy-phenylgcine （CHPG） and 3-cyano-N- （ 1,3-diphenyl- lH-pyrazol-5-yl）-Benzamide （CDPPB） after mechanical neuronal injury. Western blot was used to detect the expression changes of extracellular signal-regulated kinase （ERK）, c-jun amino acid terminal kinase （JNK）, and p38 and elucidate the mechanism underlying the neuroprotection of CHPG and CDPPB. Results LDH release and caspase-3 activity were increased after mechanical neuronal injury. Pretreatment with CHPG and CDPPB reduced the elevation of LDH release and caspase-3 activity in a dose-dependent manner. Western blot analysis indicated that pretreatment with CHPG and CDPPB significantly elevated the phosphorylation of ERK, but did not affect the phosphorylation of JNK and p38. Conclusion Two mGluR5 agonists, CHPG and CDPPB, have protective effects on mechanical neuronal injury, which might be regulated by ERK pathway.

关 键 词：代谢型谷氨酸受体5 激动剂 ERK 神经元损伤 

分 类 号：R651.15[医药卫生—外科学]