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目的:探讨小鼠蛛网膜下腔出血(subarachnoid hemorrhage,SAH)后代谢型谷氨酸受体1(metabotropicglutamate receptor 1,mGluR1)及细胞外信号调节激酶1/2(ERK1/2)调控神经细胞凋亡的分子机制。方法:采用非开颅血管内穿线法制备小鼠SAH模型,随机分为3组:假手术组、SAH+生理盐水(SAH+NS)组、SAH+LY367385(mGluR1抑制剂,SAH+LY367385)组,于SAH后10 min侧脑室注射生理盐水或LY367385(500 nmol/L)5μl,术后行神经功能评分。分别在SAH后6、24、48 h 3个时间点取右侧脑组织标本,逆转录-聚合酶链式反应(RT-PCR)检测各组mGluR1的表达变化,免疫印迹法(Western Blot)检测p-ERK1/2蛋白的表达,TUNEL法检测右侧海马CA1区神经细胞的凋亡。结果:与假手术组比较,SAH+NS组小鼠神经功能评分均显著降低(P<0.05),随SAH时间延长,各组小鼠mGluR1、p-ERK1/2蛋白均有不同程度增强,凋亡细胞增多(P<0.05)。与SAH+NS组比较,SAH+LY367385组小鼠神经功能评分增加,mGluR1、p-ERK1/2蛋白表达均有不同程度下调,神经细胞凋亡数目有所减少。SAH后6～48 h,mGluR1的表达与p-ERK1/2呈正相关。结论:mGluR1和ERK在SAH的发病机制中发挥了重要作用,SAH后海马内mGluR1的表达增强可通过激活ERK信号途径诱导神经细胞的凋亡。
AIM: To investigate the effects of metabotropic glutamate receptor 1 (mGluR1) and extracellular signal-regulated kinase 1/2 (ERK1 / 2) in the regulation of neuronal apoptosis in subarachnoid hemorrhage (SAH) mice The molecular mechanism of death. Methods: The model of SAH was established by intranasal non-craniotomy. The rats were randomly divided into 3 groups: sham operation group, SAH + NS group, SAH + LY367385 (mGluR1 inhibitor, SAH + LY367385) Ten minutes after SAH, intracerebroventricular injection of saline or LY367385 (500 nmol / L) 5μl, neurological function score. Right brain tissue samples were taken at 6, 24, and 48 h after SAH respectively. The expression of mGluR1 in each group was detected by reverse transcription-polymerase chain reaction (RT-PCR). Western Blot p-ERK1 / 2 protein expression, TUNEL method to detect the right hippocampal CA1 nerve cell apoptosis. Results: Compared with the sham operation group, the scores of neurological function in SAH + NS group were significantly decreased (P <0.05). With the prolongation of SAH time, the expression of mGluR1 and p-ERK1 / 2 protein increased Increased number of dead cells (P <0.05). Compared with the SAH + NS group, the neurological scores of SAH + LY367385 group increased, the expressions of mGluR1 and p-ERK1 / 2 decreased to some extent, and the number of neuronal apoptosis decreased. At 6 ~ 48 h after SAH, the expression of mGluR1 was positively correlated with p-ERK1 / 2. CONCLUSIONS: mGluR1 and ERK play an important role in the pathogenesis of SAH. The enhanced expression of mGluR1 in hippocampus after SAH can induce neuronal apoptosis by activating ERK signaling pathway.