电压-门控钠离子通道亚型nNav1.5在人脑胶质瘤中的表达

Expression of voltage-gated sodium channel nNav1.5 in human gliomas

目的 研究电压-门控钠离子通道（VGSCs）亚型nNav1.5在人脑胶质瘤中的表达及其与肿瘤级别的关系.方法 用免疫荧光技术检测nNav1.5蛋白在胶质瘤U251细胞株中的表达定位;按2007年WHO胶质瘤分级,将胶质瘤标本分为低级别组（WHO Ⅰ-Ⅱ级,29例）和高级别组（WHOⅢ-Ⅳ级,37例）,另外13例对照组织标本来自颅脑损伤内减压手术中切除的脑挫裂伤组织.采用RT-PCR法、免疫组化法和Western Blot法分别检测nNav1.5 mRNA和蛋白在胶质瘤组和对照组的表达情况.结果 nNav1.5主要在胶质瘤细胞核内表达,nNav1.5 mRNA和蛋白在胶质瘤组织和对照组织中均有表达,但其在胶质瘤中表达水平均显著升高（P＜0.05）,在高级别胶质瘤组的表达量亦高于低级别胶质瘤组,各组间比较差异有统计学意义（P＜0.05）.结论 nNav1.5在人脑胶质瘤中表达上调并与肿瘤的恶性程度呈正相关,nNav1.5有可能是胶质瘤恶性增殖的一个调控因子,有望成为胶质瘤的一个新标记物和治疗的新靶点.

Objective To investigate the expression of voltage--gated sodium channels （VGSCs） subunit nNavl. 5 in human gliomas and its correlation to histopathological grades. Methods According to glioma grading criteria of WHO （2007）, the gliomas from clinical samples were grouped as high grade （WHO, grade Ⅲ-Ⅳ ,37 cases） and low grade （WHO, grade Ⅰ-Ⅱ , 29 cases）. And another 13 con trol cases were brain contusion tissue from brain injury decompression surgery resection. Immunofluores- cence was used to localize the nNavl. 5 protein in glioma U251 cell. Real--time PCR, immunohistochemistry and Western blotting were used to detect nNavl. 5 mRNA and protein expression in gliomas and normal brain tissues from clinical samples, respectively. Results Immunofluorescent eonfocal microscope confirmed that nNavl. 5 protein mainly localized in nuclei of U251 cells. The expression of nNavl. 5 mRNA and protein was found in glioma groups and normal control group. Moreover, expres- sion of nNav1. 5 mRNA and protein in high grade group was statistically higher than in low grade group, and the differences were statistically significant among groups （P 〈 0. 05 for each comparison）. Conclusions nNavl. 5 was over--expressed in gliomas and was directly correlated with tumor grades, nNavl. 5 might be a regulatory factor for malignant proliferation of gliomas, therefore a potential biological marker and a new therapeutic target for gliomas.