肿瘤坏死因子-α转导的人难治性颞叶癫痫神经细胞凋亡的研究

TNF-α transduction neurocyte apotosis in refractory human temporal lobe epilepsy

目的研究人难治性颞叶癫痫(TLE)颞叶组织中是否存在肿瘤坏死因子-α(TNF-α)转导的神经细胞凋亡。方法采用免疫组化SP染色法检测30例难治性TLE(TLE组)与10例脑外伤患者的正常颞叶组织(对照组)脑组织神经元、胶质细胞中肿瘤坏死因子受体相关死亡结构域蛋白(TRADD)、凋亡信号调节激酶1(ASK1)、天冬氨酸特异性半胱氨酸蛋白酶8(caspase 8)的表达并分析其表达差异。透射电镜下观察TLE痫灶神经元、胶质细胞超微结构改变。结果TLE组神经元和胶质细胞caspase 8表达较对照组增加(分别P<0.05,P<0.01)。两组神经元与胶质细胞中均未见TRADD、ASK1明显阳性表达。透射电镜观察见TLE组神经元具有细胞体积变小、核固缩、异染色质增多及边缘化、细胞及核膜边缘皱缩不齐、核分裂像、凋亡小体形成等凋亡特征,而胶质细胞则出现水肿现象。结论人难治性TLE病颞叶组织的神经元及胶质细胞中可能存在TNF-α转导的细胞凋亡。

Objective To study whether tumor necrosis factor-α （TNF-α） transduction neurocyte apotosis exists in the temporal lobe of human refractory temple lobe epilepsy （TLE）. Methods The brain samples were obtained from 30 patients with refractory TLE （TLE group） and 10 patients with brain trauma （control group）. SP staining of immunohistochemistry was used to detect the expres- sion of TNF receptor-assosiated death domain protein （TRADD）, apoptosis-signal-regulating kinase 1 （ASK1） and caspase 8 in neu- rons and gliocytes. The ulstastructural changes of neurons, gliocytes in the foci of TLE were observed by transmission electron microscope. Results The expression of caspase 8 in neurons and gliocytes of the TLE group increased compared with that of the control group （P 〈 0.05, P 〈 0.01 respectively）. TRADD and ASK1 were not expressed in neurons and in gliocytes in the two groups. Under transmission electron microscope, distinctive apotosis changes were found in neurons of the TLE group ： the neurons becoming small in volume, nuclear pyknosis, heterochromatin increasing and marginal collection, shrinkage of cytomembrane and nucleolemma, nuclear division, and apoptotie bodies forming. Astrocytes became swollen. Conclusions TNF-α transduction cell apotosis may exist in neurons and gliocytes of the temporal lobe tissue in patients with refractory human TLE.