低级别胶质瘤合并癫患者腺苷A2A受体信号通路变化的研究  

Adenosine A2A Receptor Signaling in Low-grade Gliomas Patients with Epilepsy

作　　者：张艺帆 贺星惠 唐重阳 郭梦依 刘思奇 熊中华 栾国明[2,3] 李天富 ZHANG Ti-fan;HE Xing-hui;TANG Chong-yang;GUO Meng-yi;LIU Si-qi;XIONG Zhong-hua;LUAN Guo-ming;LI Tian-fu(Department of Neurology,Sanbo Brain Hospital,Capital Medical University,Beijing 100093,China;Department of Neurosurgery,Sanbo Brain Hospital,Capital Medical University,Beijing 100093,China;Beijing Institute for Brain Disorders,Beijing 100093,China)

机构地区：[1]首都医科大学三博脑科医院神经内科,北京100093 [2]首都医科大学三博脑科医院神经外科,北京100093 [3]北京脑重大疾病研究院,北京100093

出　　处：《中国临床神经科学》2021年第3期247-256,共10页Chinese Journal of Clinical Neurosciences

基　　金：国家自然科学基金面上项目(编号:81571275)。

摘　　要：目的研究低级别胶质瘤合并癫患者腺苷A2A受体(A2AR)信号通路的变化。方法收集10例低级别胶质瘤合并癫患者(胶质瘤合并癫组)脑肿瘤标本,另选择6例局灶性皮质发育不良ⅡB型患者(局灶性皮质发育不良组)手术切除的癫病灶周边组织为对照。利用免疫组化法检测标本中CD39、CD73、A2AR、谷氨酸转运蛋白-1(GLT-1)和蛋白激酶A(PKA)的表达水平;蛋白印迹法检测A2AR的表达水平。结果伴有癫发作的胶质瘤患者脑肿瘤标本CD39(P<0.05)、CD73(P<0.05)、A2AR(P<0.01)和PKA表达(P<0.05)上调,GLT-1表达下调(P<0.05);A2AR和PKA存在免疫共定位。结论A2AR表达上调可通过降低GLT-1活性以及增加PKA活性,促进胶质瘤相关癫的发生。A2AR可能是治疗胶质瘤相关癫的靶点。Aim To study the adenosine A2A receptor(A2AR)signaling pathway in low-grade gliomas patients with epilepsy.Methods Obtained brain specimens from 10 low-grade gliomas patients with epilepsy(gliomas with epilepsy group),and specimens from 6 focal cortical dysplasia ⅡB patients(the control group).Immunohistochemistry approach was used to examine the expression of CD39,CD73,A2AR,glutamate transporter-1(GLT-1)and protein kinase A(PKA).The qualification of A2AR expression in gliomas versus controls was evaluated by Western blot.Results Upregulation of CD39(P<0.05),CD73(P<0.05),A2AR(P<0.01),PKA(P<0.05),downregulation of GLT-1(P<0.05)were observed in gliomas with epilepsy group.Doubling staining demonstrated marked colocalization of A2AR and PKA in tumor cells.Conclusion These results suggested that upregulation of A2AR,by decreasing GLT-I activity and increasing PKA activity might trigger the development of epilepsy related with gliomas.A2AR might be a target in the treatment of epilepsy associated with gliomas.

关 键 词：胶质瘤 癫 腺苷A2A受体 谷氨酸转运蛋白-1 蛋白激酶A 

分 类 号：R742.1[医药卫生—神经病学与精神病学] R730.264[医药卫生—临床医学]