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目的自噬流增强或减弱均参与耐药性颞叶癫痫(Temporal lobe epilepsy,TLE)的病理生理过程,海马硬化(Hippocampal sclerosis,HS)是耐药性TLE主要的病理类型。但不同亚型HS不仅预后有差异,其病因、病理生理也存在差异。而自噬流异常阻滞是否参与其中,目前尚罕见报道,研究拟初步比较典型及非典型HS患者自噬流情况,探讨非典型HS患者可能的发生及耐药机制。方法收集2015年3月-2015年12月于华西医院就诊的耐药性TLE患者17例,手术切除海马及颞叶癫痫灶。根据2013年国际抗癫痫联盟HS病理分型标准分组,分为10例典型HS组(HS1型),7例非典型HS组(HS2型6例+HS3型1例),并对手术切除组织采用免疫组织化学及免疫印迹检测LC3B、Beclin-1及P62表达分布及表达量。结果与既往报道一致,LC3B、Beclin-1及P62主要表达于神经元细胞浆。以β-actin为内参,非典型HS组较典型HS组,自噬流下游产物LC3B、Beclin-1有明显升高(P<0.01),非典型HS组出现了自噬底物的堆积和自噬流不畅,而自噬流底物P62在组间无差异;同时发现3-磷酸甘油醛脱氢酶(GAPDH)在两组间有极显著差异(P=0.003)。结论非典型HS中存在自噬流异常阻滞现象,并且GAPDH可能参与到其机制中,这为未来治疗手术效果不佳的非典型HS提供了新的靶点和思路。
Objective To investigate the pathophysiological process of drug-resistant temporal lobe epilepsy (TLE), and to study whether Hippocampal sclerosis (HS) is the major pathological type of drug resistant TLE. However, different subtypes of HS not only have different prognosis, its etiology, pathophysiology are also different. Whether autophagy abnormal block is involved in it is still rarely reported. It is proposed to compare the typical autophagy in patients with atypical HS and the possible pathogenesis of atypical HS and the mechanism of drug resistance. Methods 17 cases of resistant TLE patients treated in West China Hospital from March 2015 to December 2015 were collected. The hippocampus and temporal lobe epileptic foci were surgically removed. According to the 2013 International Antiepileptic League HS pathological classification standard group, divided into 10 cases of typical HS group (HS1 type), 7 cases of atypical HS group (HS2 type 6 cases + HS3 type 1 case), and the surgical removal of tissue Immunohistochemistry and Western blotting were used to detect the expression and distribution of LC3B, Beclin-1 and P62. Results consistent with previous reports, LC3B, Beclin-1 and P62 mainly expressed in neuronal cytoplasm. With β-actin as an internal control, the atypical HS group had significantly higher LC3B and Beclin-1 than the typical HS group (P <0.01), and atypical HS group, However, there was no difference between the two groups. P-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was found to be significantly different between the two groups (P = 0.003). Conclusion Abnormal autonomic flow block exists in atypical HS, and GAPDH may participate in its mechanism. This may provide new targets and ideas for the treatment of atypical HS with poor therapeutic effect in the future.