目的 探索利美尼定(RIL)对肌萎缩侧索硬化(ALS)相关蛋白质TAR DNA结合蛋白43(TDP-43)降解的影响.方法 用瞬时转染的方法在运动神经元样细胞系NSC-34中过表达WT TDP-43,与家族型ALS相关的Q331K TDP-43、M337V TDP-43突变蛋白、TDP-43的两种C末端片段TDP-25和TDP-35,再给予利美尼定干预16h,通过蛋白印迹方法检测5种TDP-43的表达水平.结果 在自噬诱导剂RIL的作用下,两种突变TDP-43及其C末端片段的表达明显减少,而WT TDP-43的蛋白质表达水平无明显变化.在自噬阻断剂3-MA的干预下,RIL降解异常蛋白质的作用也被阻断.结论 RIL可经由自噬通路降解Q331K TDP-43、M337V TDP-43及其C末端截短片段.

目的 利美尼定对家族性肌萎缩侧索硬化症(ALS)相关突变蛋白质SOD1G93A的作用机制.方法 用瞬时转染的方法在运动神经元样细胞系NSC-34中过表达WTSOD1,与家族型ALS相关的SOD1G93A突变蛋白,再给予自噬通路的特异性诱导剂和阻断剂,通过Western blot蛋白印迹法检测突变SOD1、自噬标记物的蛋白质表达水平.结果 自噬诱导剂trehalose可以使SOD1G93A蛋白质表达水平明显减少.在自噬阻断剂3-甲基腺嘌呤(3-MA)的干预下,SOD1G93A蛋白质表达水平明显升高.l0uM利美尼定能够明显降低G93A SOD1的表达,但对WT SOD1的表达水平无明显影响.结论 SOD1G93A主要经由自噬途径降解,利美尼定能够明显促进G93A SOD1的降解,但对WT SOD1的蛋白质表达水平无明显促进作用.

自噬是一种基础的分解代谢过程，与细胞的存活、分化、发育和内环境稳态的维持密切相关。近年来研究发现，自噬在清除神经变性疾病相关的错折叠蛋白质和易聚集蛋白质方面起着重要作用。本文就自噬及其在神经变性疾病领域的研究做一综述。

目的 探索肌萎缩侧索硬化症(ALS)相关TDP-43的降解机制.方法 用瞬时转染的方法在运动神经元样细胞系NSC-34中过表达野生型(role of wild-type,WT) WT TDP-43,与家族型ALS相关的Q331K TDP-43、M337V TDP-43突变蛋白、TDP-43的两种C末端片段TDP-25和TDP-35,再给予自噬、蛋白酶体通路的特异性诱导剂和阻断剂,通过蛋白印迹方法检测5种TDP-43以及自噬标记物LC3-Ⅱ的表达水平.结果 在自噬诱导剂作用下,各组LC3-Ⅱ的表达升高,同时两种突变TDP-43及其C末端片段的表达明显减少,在自噬通路和蛋白酶体阻断剂作用下突变TDP-43及其C末端片段表达水平明显增多,而WT TDP-43的蛋白表达水平仅在蛋白酶体阻断剂作用时增多.结论 WT TDP-43主要经由蛋白酶体途径降解,Q331K TDP-43、M337V TDP-43及其C末端片段经由蛋白酶体途径和自噬两种途径降解.

Objective To investigate the relationship between the Lp-PLA2 and ischemic cerebrovascular to predict the occurrence of ischemic cerebrovascular disease with accurate simple and quick method. Methods Selectly 98 cases of cerebral infarction in patients as the case group and 30 cases of healthy subjects as control group, 98 cases of the case group include TIA group 21 cases,asymptomatic cerebral infarction group 31 cases,symptomatic cerebral infarction group 46 cases. The case group and control group were to detect the plasma Lp-PLA2 level by double antibody enzyme linked immunosorbent assay( ELISA),while detecting the plasma CHOL,TG,LDL-C, HDL-C level. Results ①The Lp-PLA2 levels of in the case group were significantly higher than the control group and had statistically significant( P 0. 01). ② The Lp-PLA2 levels of symptomatic cerebral infarction group were significantly higher than both TIA group and asymptomatic cerebral infarction group. The differences among three group had statistically significant( P0.01). ③The Lp-PLA2 levels of the asymptomatic cerebral infarction group were higher than the TIA group.The differences between two group had statistically significant( P 0.01).Conclusion Plasma Lp-PLA2 may be associated with the severity of ischemic cerebrovascular disease and we speculate that the Lp-PLA2 possibly becomes to a biological indicators,which predicts risk of the ischemic cerebrovascular diseases.

Objective: To detect the association between the levels of plasma lipoprotein-associated phospholipase A2( Lp- PLA2) and carotid artery plaque. Methods: Selected 72 cases of cerebral infarction in patients as the case group and 30 cases of healthy subjects as control group,and the case group were accepted carotid artery color doppler ultrasound. The plasma Lp-PLA2 level were detected by double antibody enzyme linked immunosorbent assay( ELISA) in case group and control group,while the plasma CHOL,TG,LDL-C,HDL-C level were detected at the some time. Results: The case group included 23 were unstable plaque group, 23 were stable plaque group,15 with mixed plaques and 11 were no plaque group,the plasma Lp-PLA2 levels of the case group were higher than the control group,and the difference was statistical significance( P < 0. 05). The plasma Lp-PLA2 levels of the unstable atheromatous plaque group are higher than any other groups; the plasma Lp-PLA2 levels of the mixed plaques group were higher than the stable plaque and no plaque group; the plasma Lp-PLA2 levels of the stable plaque group were higher than no plaque group; all of the differences had statistical significance( P < 0. 05). Conclusion: Plasma Lp-PLA2 levels could be a predicted biological marker of unstable carotid plaques.