新型机械激活离子通道Piezo2蛋白在癫痫患者脑组织中的表达和作用

Expression and effect of Piezo2 protein in brain tissues of epileptic patients

目的探究新型机械激活离子通道Piezo2蛋白在癫痫患者脑组织中的表达和作用。方法本研究以2015年10月至2018年1月我院收治的54例癫痫患者和21例脑外伤患者为研究对象,癫痫组的脑组织为难治性癫痫患者手术中所得,对照组的脑组织为脑外伤患者术中取得。利用RT-PCR,Western blot和免疫组化方法检测癫痫组患者和对照组患者脑组织中Piezo2的表达,利用免疫荧光定位Peizo2蛋白在皮质组织和海马组织中的表达,利用免疫共沉淀实验检测蛋白-蛋白的相互作用,确定Piezo2的下游信号分子。结果癫痫患者皮质组织中Piezo2蛋白表达量明显高于对照组,与微管相关蛋白2(MAP2)共存,但不与胶质纤维酸性蛋白(GFAP)共存。癫痫患者脑组织Piezo2蛋白和mRNA表达量明显高于脑外伤对照组,Piezo2的下游信号分子为ERK5和TGF-β,通过EKR5/MAPK和TGF-β信号通路起到信息传递的作用。结论新型机械敏感性离子通道Piezo2蛋白激活促进癫痫的进展,与ERK5/MAPK和TGF-β信号通路相关。

Objective To investigate the expression and effect of Piezo2 protein in epileptic brain tissue. Methods From October 2015 to January 2018, 54 patients with epilepsy and 21 patients with brain trauma in neurosurgery department of our hospital were studied. The brain tissues were obtained during the operation of intractable epilepsy patients, while those of control group were obtained during the operation of brain trauma patients. Piezo2 expression was detected by RT-PCR, Western blot and immunohistochemistry in brain tissue. The expression of Peizo2 protein in cortex and hippocampus was localized by immunofluorescence. The protein-protein interaction was detected by immunoprecipitation assay, and the downstream signal molecule of Piezo 2 was determined. Results Piezo2 protein expression level in cortex was significantly higher in epilepsy patients than in control, with colocolization with microtubule associated protein 2(MAP2) in cortex of epileptic patients but not co-staining with glial fibrillary acidic protein(GFAP). The expression levels of Piezo2 in brain tissue were significantly higher in epilepsy patients than in traumatic brain control. The downstream signal molecule of Piezo2 were ERK5 and TGF-βthat play an important role in information transmission via EKR5/MAPK and TGF-βsignaling pathways. Conclusion Piezo2 protein activation promoted the progression of epilepsy via ERK5/MAPK and TGF-beta signaling pathways.