mTOR信号通路在脑胶质瘤相关癫痫中的作用研究  

Role of mTOR signaling pathway in glioma-associated seizures

作　　者：杨渊[1] 王翔[1] 梁若飞[1] 罗杰文[1] 姜曙[1] 毛庆[1] Yang Yuan;Wang Xiang;Liang Ruofei;Luo Jiewen;Jiang Shu;Mao Qing(Department of Neurosurgery,West China Hospital,Sichuan University,Chengdu 610041,China)

机构地区：[1]四川大学华西医院神经外科,成都610041

出　　处：《中华神经外科杂志》2020年第2期151-155,共5页Chinese Journal of Neurosurgery

基　　金：四川大学火花库项目(2082604401004/060)。

摘　　要：目的探讨mTOR信号通路在脑胶质瘤相关癫痫(GAS)中的作用。方法回顾性分析2016年1月至6月四川大学华西医院神经外科收治的12例脑胶质瘤患者的临床资料。12例患者中,9例存在GAS,另3例不存在。所有患者均采用肿瘤切除术治疗,术中均留取肿瘤组织、瘤周组织及瘤周正常组织标本。采用脑片膜片钳记录组织标本的神经电生理情况,以明确是否存在GAS病灶;之后行蛋白质免疫印迹和免疫组织化学染色实验,以判断mTOR通路是否与GAS相关。结果12例患者中,7例存在GAS患者的瘤周组织均检测到痫样放电,电位峰值为0.300^-0.429 mV,斜率为1.502 mV/ms;而在其肿瘤组织和正常脑组织中均未检测到痫样放电;另2例存在GAS患者和3例不存在GAS患者,其肿瘤组织、瘤周组织及正常脑组织中均未检测到痫样放电。蛋白质免疫印迹结果显示,存在GAS患者的瘤周组织中p-mTOR(相对表达量为1.002)和p-S6K(相对表达量为0.926)的表达量均显著高于不存在GAS的患者(相对表达量分别为0.756、0.661,均P<0.05),而两者间mTOR(相对表达量分别为1.233、1.178)和S6K(相对表达量分别为0.925、0.917)表达量的差异均无统计学意义(均P>0.05)。存在GAS患者和不存在GAS患者的肿瘤组织中p-mTOR、mTOR、p-S6K及S6K表达量的差异均无统计学意义(均P>0.05)。免疫组织化学染色结果显示,9例GAS患者中,8例的瘤周组织中p-S6K和p-mTOR染色均为阳性,而未发生GAS的3例患者瘤周组织中p-S6K和p-mTOR染色均为阴性;存在GAS患者和不存在GAS患者的肿瘤组织中p-S6K和p-mTOR染色均为阳性。结论初步提示脑胶质瘤瘤周组织mTOR信号通路激活与GAS有关,可能是同时治疗胶质瘤和癫痫发作的共同靶点。Objective To investigate the role of mTOR signaling pathway in glioma-associated seizures(GAS).Methods We retrospectively analyzed 12 glioma patients admitted to Department of Neurosurgery,West China Hospital,Sichuan University from January 2016 to June 2016.Among the 12 glioma patients,9 had glioma GAS and 3 did not.All patients enrolled into this study underwent tumor resection.After surgery,the neuroelectrical activities of tumor tissue,peritumoral tissue and peritumoral normal tissue were documented by patch clamping recording of brain slices to clarify the GAS lesions,followed by Western blotting and immunohistochemical experiments to confirm whether mTOR pathway activation was related to GAS.Results Interictal-like discharges(ILDs)were observed in 7 of 12 peritumoral tissues obtained from patients with glioma who had experienced perioperative seizures.Their peak amplitude ranged from 0.300 mV to-0.429 mV and the slope was 1.502 mV/ms.However,their tumor and normal tissue samples didn′t show ILDs.No ILDs were observed in the tumor tissue,peritumoral or normal tissue of 2 patients with GAS and 3 patients without GAS.The results of Western blotting showed that peritumoral expressions of p-mTOR(relative expression value:1.002)and p-S6K(relative expression value:0.926)of patients with GAS were significantly higher than those of patients without GAS(relative expression Value:0.756 and 0.661,both P<0.05),while their mTOR(relative expression value:1.233 vs.1.178)and S6K expression(relative expression value:0.925 vs.0.917)expression levels had no significant difference(both P>0.05).There was no statistical significance in the expression of p-mTOR,mTOR,p-S6K or S6K in the tumor tissues between patients with GAS and those without GAS(all P>0.05).Immunohistochemical staining results showed that p-S6K and p-mTOR stainings were positive in the peritumoral tissues in 8 of 9 patients with GAS,while they were negative in 3 patients without GAS.Both p-S6K and p-mTOR staining were positive in tumor tissues of patients with

关 键 词：神经胶质瘤 癫痫 MTOR信号通路 

分 类 号：R73[医药卫生—肿瘤] R742[医药卫生—临床医学]