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目的研究瞬时受体电位通道蛋白5(transient receptor potential canonical channel 5,TRPC5)在结节性硬化症(tuberous sclerosis complex,TSC)癫痫患者皮质中的表达与分布,探讨TRPC5在TSC癫痫发生中的可能机制。方法收集新桥医院神经外科手术切除的TSC癫痫患者皮层致痫结节14例,与12例正常对照皮层(CTX)相比较,运用RT-PCR、Western blot、免疫组织化学和免疫荧光等方法检测TRPC5在致痫灶中的表达分布。结果 TSC癫痫患者皮层致痫结节中,TRPC5在mRNA、蛋白表达水平较对照组明显升高(P<0.05)。免疫组化结果显示,在正常皮层中TRPC5弱至中等强度表达于神经元上,偶在胶质细胞上表达,而在TSC癫痫患者皮层致痫结节中强表达于神经元上,特别是巨型细胞和异形神经元上,胶质细胞表达强度也较CTX组增高,免疫染色强度明显高于正常皮层(染色强度值:2.77±0.43 vs 1.64±0.56;相对光密度值:64.72±9.56 vs 30.34±9.43;P<0.05)。结论 TRPC5表达增高可能与TSC患者癫痫发病密切相关,可能成为治疗难治性癫痫的新药物靶点。
Objective To investigate the expression and distribution of transient receptor potential canonical channel 5 (TRPC5) in the cortex of epileptic patients with tuberculous sclerosis complex (TSC), and to explore the possible role of TRPC5 in epileptogenesis of TSC mechanism. Methods Totally 14 cases of epileptic nodules were collected from patients with TSC epilepsy in Xinqiao Hospital. Compared with CTX, 12 cases of TSC epilepsy were detected by RT-PCR, Western blot, immunohistochemistry and immunofluorescence Expression and distribution of TRPC5 in epileptogenic zone. Results The expression of TRPC5 mRNA and protein in epileptic nodules of epileptic patients with TSC was significantly higher than that of the control group (P <0.05). Immunohistochemical results showed that in normal cortex, TRPC5 expressed weakly to moderately on neurons, even on glial cells, whereas it was strongly expressed on neurons in epileptic nodules of cortex of TSC patients, especially in giant Compared with CTX group, the intensity of immunostaining was significantly higher than that of normal cortex (staining intensity value: 2.77 ± 0.43 vs 1.64 ± 0.56; relative optical density value: 64.72 ± 9.56 vs 30.34 ± 9.43; P <0.05). Conclusion The increased expression of TRPC5 may be closely related to the onset of epilepsy in TSC patients and may be a new drug target for the treatment of refractory epilepsy.