目的 探讨谷氨酸对HT22细胞线粒体自噬和细胞凋亡的影响,并评估虾青素预处理的保护作用及其分子机制。方法 用谷氨酸及虾青素处理HT22细胞,通过蛋白印迹及聚合酶联反应等评估其对线粒体自噬的影响。结果 谷氨酸处理显著抑制线粒体初级自噬（PINK1、Parkin、pULK1ser555和LC3Ⅱ）和次级自噬（LAMP1和Rab7）,上调cleaved Caspase-3的表达（P<0.05）。虾青素预处理减少细胞凋亡,恢复了线粒体自噬,PINK1、Parkin、pULK1ser555和LC3Ⅱ的表达水平上升（分别为2.3倍、2.6倍、83.3%及81.1%）（P<0.05）,该作用被自噬抑制剂BafA1阻断。此外,谷氨酸抑制Nrf2核内转移和NLRX1表达,而预处理显著促进Nrf2的核内转移并上调NLRX1,分别上调25.8%、33.2%。生物信息学分析显示NLRX1启动子区域含有3个Nrf2结合位点,提示Nrf2通过调控NLRX1转录活性发挥作用。结论 文章首次揭示虾青素通过Nrf2/NLRX1通路激活线粒体自噬,展现神经保护作用。
Objective To explore the effects of glutamate on mitophagy and apoptosis in HT22 cells and evaluate the protective effects and molecular mechanisms of astaxanthin pretreatment．Methods HT22 cells were treated with glutamate and astaxanthin．The effects on mitophagy were assessed using Western Blot and PCR．Results Glutamate treatment significantly inhibited primary mitophagy（PINK1,Parkin,pULK1ser555 and LC3II）and secondary mitophagy（LAMP1 and Rab7）while upregulating cleaved Caspase-3 expression．Astaxanthin pretreatment notably reduced apoptosis and restored mitophagy,the expression levels of PINK1,Parkin,pULK1Ser555 and LC3II were significantly upregulated（by 2.3-fold,2.6-fold,83.3% and 81.1% respectively,P<0.05）,but this effect was blocked by the autophagy inhibitor BafA1．Additionally,glutamate suppressed Nrf2 nuclear translocation and NLRX1 expression,whereas astaxanthin promoted Nrf2 nuclear translocation and increased NLRX1 expression by 25.8% and 33.2%,respectively．Bioinformatics analysis revealed three Nrf2 binding sites in the NLRX1 promoter region,suggesting that Nrf2 may regulate NLRX1 transcriptional activity．Conclusions The study demonstrates that astaxanthin exhibited potential neuroprotective effect by activating mitophagy through the Nrf2/NLRX1 pathway．
阿尔茨海默病（Alzheimer's disease,AD）是一种复杂的、起病隐秘的、病因不明的、缺乏特异性诊断方式的神经退行性病变。面对与日俱增的患病率,却缺乏有效的治疗方式。中医药治疗方式具有多层次、多靶点、多通路的独特优势,中西医结合方式的互补,非药物疗法的辅助,干细胞疗法、新的分子药物、抗体及蛋白疫苗、γ感官刺激等新颖的实验阶段新疗法等方式治疗AD。本文综述近年来的不同治疗方式治疗AD研究新进展,旨在为临床上治疗AD提供新思路、新方法及参考价值。
Alzheimer's disease is a complex,secrectly onset neurodegenerative disease with unknown etiology,and lacking of specific diagnosis．In the face of the increasing prevalence,there is a lack of effective treatment ways．The treatment of traditional Chinese medicine has the unique advantages of multi-level,multi-target,and multi-channel．With the combination of traditional Chinese and Western medicine and supplement to non-drug therapy,stem cell therapy,new molecular drugs,antibodies and protein vaccines,γ sensory stimulation,and other novel experimental stage new therapies are uesd in the treatment of AD．The article focuses on the new progress of different treatment methods in the treatment of AD in recent years,aiming to provide new ideas,new methods,and reference value for the clinical treatment of Alzheimer's disease．
目的 探讨具有不同载脂蛋白E4等位基因(Apolipoprotein E4 alleles,APOE4)阿尔茨海默病患者的神经心理学量表差异。方法 纳入2014年1月—2017年12月广州市第一人民医院收治阿尔茨海默病患者28人,分别予简易精神状态检查量表、阿尔茨海默病评定量表-认知部分、临床医师通过面谈对变化的印象、日常生活活动能力量表、神经精神问卷,并检测量表间相关关系。之后随访18个月,观察量表评测的各功能变化及互相间相关性。检测不同载脂蛋白E4等位基因等阿尔茨海默病相关基因分布及与量表间相关关系。结果 认知评定量表间、认知评定量表与整体评价量表间、以及认知评定量表与日常活动能力评定量表间具有相关性。精神与行为症状量表分数与其他评定量表无明显相关性。随访中各量表分数变化间均无相关性。各基因组间功能变化无显著性差异,载脂蛋白E4等位基因变异主要影响患者的认知功能。等位基因分布与患病年龄,日常活动能力及精神与行为症状无相关性。结论 阿尔茨海默病量表评测的各认知领域间相关性不同,功能变化间无相关关系。载脂蛋白E4等位基因变异主要影响患者的认知功能。
Objective The present study aimed to elucidate the performance of multiple psychological tests among different Apolipoprotein E4 alleles (APOE4) in people with Alzheimer's disease (AD). Methods 28 patients were enrolled from January 2014 to December 2017 in Guangzhou First People'S Hospital. All patients were tested by using Mini-mental State Examination (MMSE), Alzheimer's disease Assessment Scale (ADAS-cog), Clinician's Interview-Based Impression of Change (CIBIC-Plus), Activities of Daily Living (ADL) and the NeuroPsychiatric Inventory (NPI). After 18 months follow-up visit, the change of the tests points were recorded. AD pathogenic genes, including Apolipoprotein E4 allele's variations, were detected in all patients. Then the correlations of APOE4 alleles and multiple psychological tests were analyzed. Results The correlations were confirmed between MMSE and ADAS-cog, MMSE and CIBIC-plus, MMSE and ADL, ADAS-cog and CIBIC-plus, ADAS-cog and ADL. NPI showed no correlation with the others. No correlation was found between changes of multiple psychological tests after 18 months follow-up. APOE4 alleles' variation affected cognitive function mainly. The effects of APOE4 on ADL and NPI showed no statistical significance in AD patients. No correlation was found among patients groups with different APOE4 alleles in all psychological tests and age of onset. Conclusion The correlations were existed among multiple cognitive domains while levels were different. The changes between psychological tests showed no correlations. APOE4 alleles' variation affected cognitive function mainly.
目的 探讨载脂蛋白E基因多态性在COPD患者合并AD中的意义。方法 通过病例资料进行回顾性研究,收集慢性阻塞性肺疾病70例,阿尔茨海默病81例,健康对照人群566例,进行统计分析。结果 “AD组”和“COPD合并AD组”的LDL水平高于“COPD未合并AD组”;“COPD组”的ApoE水平高于“AD组”,且在“COPD组”中,未合并AD者的ApoE水平明显高于合并AD者;“COPD组”的ε3/ε4基因型均少于“AD组”,且“COPD未合并AD组”的ε3/ε4基因型明显少于“COPD合并AD组”;“AD组”及“COPD合并AD组”的ε4等位基因频率多于“COPD组”及“COPD未合并AD组”;“COPD合并AD组”的ε3/ε3基因型少于“健康对照组”,而ε2/ε4基因型则多于“健康对照组”;“COPD组”的ε3/ε4基因型多于“健康体检组”;“COPD合并AD组”的ε3/ε4基因型多于“健康体检组”;“COPD合并AD组”的ε4等位基因频率高于“健康对照组”。结论 ApoE基因多态性不但参与COPD患者认知功能受损甚至合并AD,而且可能通过影响脂质代谢,参与COPD的发生发展;ApoE的ε4等位基因可能是COPD和AD患病的共同危险因素。
目的 探讨老年人血尿酸(serum uric acid,SUA)水平与阿尔茨海默病(Alzheimer's disease,AD)的相关性。方法 选择227例我院老年病科住院患者为研究对象,其中阿尔茨海默病67例,其余160例为非AD组。收集病史、吸烟史、服药史,并检测血尿酸、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、空腹血糖(FBS)、血肌酐(Cr)水平。比较各SUA四分位数水平AD的发生率,并进行相关性分析。结果 AD组血尿酸水平低于非AD组,差异有统计学意义(P＜0.01);多因素分析筛选出年龄、性别、缺血性脑卒中是危险因素(P＜0.05),而服用他汀、SUA、HDL-C是保护因素(P＜0.05)。对AD和SUA的四个分组做Spearman等级相关分析(rs=-0.285,P<0.001),结果呈等级负相关。结论 血尿酸水平与老年人AD相关,血尿酸可能是AD发病的保护性因素。
Objective To explore the correlation between serum uric acid(SUA) level and Alzheimer's disease(AD) in elderly patients. Methods 67 cases of the elders with Alzheimer's disease and 160 elders matching with age and gender were enrolled from Jan 2013 to Dec 2014 in the study,the blood levels of biochemical factors such as SUA,total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),fasting blood sugar(FBS) and creatinine(Cr) were measured by automatic biochemistry analyzer in the two groups. The related factors such as history of disease,smoking and medication history were collected. The correlation between the level of SUA and AD was analyzed. Results The serum uric acid levels in AD group were significantly lower than those in control group(P＜0.01). Multivariate logistic regression analysis showed that age, gender, ischemic stroke were risk factors, and taking statin, SUA, and HDL-C were protective factors(P＜0.05). Spearman correlation tests indicated that there was an inverse correlation between SUA levels and AD(rs=-0.285,P<0.001). Conclusion Serum uric acid level is significantly related to AD in the elderly.SUA may be a protective factor of the occurrence of AD.
目的 探讨谷氨酸对HT22细胞线粒体自噬和细胞凋亡的影响，并评估虾青素预处理的保护作用及其分子机制。方法 用谷氨酸及虾青素处理HT22细胞，通过蛋白印迹及聚合酶联反应等评估其对线粒体自噬的影响。结果 谷氨酸处理显著抑制线粒体初级自噬（PINK1、Parkin、pULK1ser555和LC3Ⅱ）和次级自噬（LAMP1和Rab7），上调cleaved Caspase-3的表达（P＜0.05）。虾青素预处理减少细胞凋亡，恢复了线粒体自噬，PINK1、Parkin、pULK1ser555和LC3Ⅱ的表达水平上升（分别为2.3倍、2.6倍、83.3%及81.1%）（P＜0.05），该作用被自噬抑制剂BafA1阻断。此外，谷氨酸抑制Nrf2核内转移和NLRX1表达，而预处理显著促进Nrf2的核内转移并上调NLRX1，分别上调25.8%、33.2%。生物信息学分析显示NLRX1启动子区域含有3个Nrf2结合位点，提示Nrf2通过调控NLRX1转录活性发挥作用。结论 文章揭示虾青素通过Nrf2/NLRX1通路激活线粒体自噬，展现神经保护作用。
Objective To explore the effects of glutamate on mitophagy and apoptosis in HT22 cells and evaluate the protective effects and molecular mechanisms of astaxanthin pretreatment．Methods HT22 cells were treated with glutamate and astaxanthin．The effects on mitophagy were assessed using Western Blot and PCR．Results Glutamate treatment significantly inhibited primary mitophagy（PINK1，Parkin，pULK1ser555 and LC3II）and secondary mitophagy（LAMP1 and Rab7）while upregulating cleaved Caspase-3 expression．Astaxanthin pretreatment notably reduced apoptosis and restored mitophagy，the expression levels of PINK1，Parkin，pULK1ser555 and LC3II were significantly upregulated（by 2.3-fold，2.6-fold，83.3% and 81.1% respectively，P＜0.05），but this effect was blocked by the autophagy inhibitor BafA1．Additionally，glutamate suppressed Nrf2 nuclear translocation and NLRX1 expression，whereas astaxanthin promoted Nrf2 nuclear translocation and increased NLRX1 expression by 25.8% and 33.2%，respectively．Bioinformatics analysis revealed three Nrf2 binding sites in the NLRX1 promoter region，suggesting that Nrf2 may regulate NLRX1 transcriptional activity．Conclusions The study demonstrates that astaxanthin exhibited potential neuroprotective effect by activating mitophagy through the Nrf2/NLRX1 pathway．
