Interacting with α7 nAChR is a new mechanism for AChE to enhance the inflammatory response in macrophages

Acetylcholine (ACh) regulates inflammation via α7 nicotinic acetylcholine receptor (α7 nAChR). Acetylcholinesterase (AChE), an enzyme hydrolyzing ACh, is expressed in immune cells suggesting non-classical function in inflammatory responses. Here, the expression of PRiMA-linked G4 AChE was identified on the surface of macrophages. In lipopolysaccharide-induced inflammatory processes, AChE was upregulated by the binding of NF-κB onto the ACHE promotor. Conversely, the overexpression of G4 AChE inhibited ACh-suppressed cytokine release and cell migration, which was in contrast to that of applied AChE inhibitors. AChEmt, a DNA construct without enzymatic activity, was adopted to identify the protein role of AChE in immune system. Overexpression of G4 AChEmt induced cell migration and inhibited ACh-suppressed cell migration. The co-localization of α7 nAChR and AChE was found in macrophages, suggesting the potential interaction of α7 nAChR and AChE. Besides, immunoprecipitation showed a close association of α7 nAChR and AChE protein in cell membrane. Hence, the novel function of AChE in macrophage by interacting with α7 nAChR was determined. Together with hydrolysis of ACh, AChE plays a direct role in the regulation of inflammatory response. As such, AChE could serve as a novel target to treat age-related diseases by anti-inflammatory responses.     

盐酸多奈哌齐联合尼莫地平治疗血管性痴呆的疗效

目的：观察盐酸多奈哌齐联合尼莫地平治疗血管性痴呆的临床疗效。方法：血管性痴呆患者60例,随机分为观察组和对照组,对照组服用盐酸多奈哌齐（5 mg/d）,每晚临睡前口服;观察组在对照组的用药基础上联用尼莫地平片30 mg,3次/d ,疗程8周;采用简易精神状态检查表（ mmSE）、临床痴呆量表（ CDR）及日常生活自理量表（ ADL）于治疗前、治疗4周及治疗8周时对2组患者进行评分,评价疗效,同时观察两组不良反应。结果：观察组治疗后 mmSE、CDR及 ADL评分均较治疗前明显改善,差异有统计学意义（ P <0.01,P <0.05,P<0.01）;对照组治疗后mmSE、CDR评分较治疗前明显改善,差异有统计学意义（ P<0.01,P<0.05）, ADL分数虽较治疗前减少,但差异无统计学意义（ P>0.05）,两组均无严重不良反应。结论：盐酸多奈哌齐联合尼莫地平治疗血管性痴呆的疗效优于单独使用盐酸多奈哌齐。     

Donepezil improves obstructive sleep apnea in Alzheimer disease: a double-blind, placebo-controlled study

BACKGROUND: There is an association between Alzheimer disease and sleep-disordered breathing. Donepezil is the drug most frequently used to treat cognitive symptoms in Alzheimer disease. This study evaluates the effects of donepezil on obstructive sleep apnea in patients with Alzheimer disease. METHODS: Randomized, double-blind, placebo-controlled design. Twenty-three patients with mild-to-moderate Alzheimer disease and apnea-hypopnea index (AHI) > 5/h were allocated to two groups: donepezil treated (n = 11) and placebo treated (n = 12). Polysomnography and cognitive evaluation using Alzheimer disease assessment scale-cognitive (ADAS-cog) subscale were performed at baseline and after 3 months. Cognitive and sleep data were analyzed using analysis of variance. RESULTS: AHI and oxygen saturation improved significantly after donepezil treatment compared to baseline and placebo (p < 0.05). Rapid eye movement (REM) sleep duration increased after donepezil treatment (p < 0.05). ADAS-cog scores improved after donepezil treatment, although they did not correlate with REM sleep increase and sleep apnea improvement (p < 0.01). CONCLUSIONS: Donepezil treatment improved AHI and oxygen saturation in patients with Alzheimer disease. Treatment also increased REM sleep duration and reduced ADAS-cog scores. Trial registration: ClinicalTrials.gov Identifier: NCT00480870.     

亲水凝胶骨架材料制备盐酸多奈哌齐缓释片的可行性研究

目的 采用亲水凝胶骨架材料制备盐酸多奈哌齐缓释片,并对其质量进行评价。方法 采用亲水凝胶骨架材料HPMC K100LV和K4M联用通过干法制粒工艺制备盐酸多奈哌齐缓释片,以溶出曲线相似性f2值作为评价指标,通过正交设计进行处方优化,用高效液相色谱法进行含量和杂质检测,通过加速和长期试验考察片剂稳定性。结果 以该方法制备的盐酸多奈哌齐缓释片质量稳定,具有与原研制剂一致的溶出特征。结论 以该方法制备盐酸多奈哌齐缓释片具有可行性。     

中西医结合治疗阿尔茨海默病临床研究

目的:观察中西医结合治疗阿尔茨海默病的临床疗效。方法:120例阿尔茨海默病患者随机平均分为对照组、普通治疗组和综合治疗组。其中对照组给予盐酸多奈哌齐片;普通治疗组给予盐酸多奈哌齐片+补肾益智颗粒+针刺治疗等疗法;综合治疗组给予口服盐酸多奈哌齐片+补肾益智颗粒+针刺治疗+经颅电刺激等疗法。各组分别在治疗前与治疗后4周、8周、12周、16周、20周、24周进行阿尔茨海默病评定(Alzheimer’s disease assessment scale,ADAS-cog)量表、简易精神状态检查(mini-mental state examination,MMSE)量表及日常生活活动能力评定(activities of daily living,ADL)量表评分。结果:对照组、普通治疗组、综合治疗组治疗后MMSE量表评分均升高(P<0.05);3组治疗后ADAS-cog量表及ADL量表评分均降低(P<0.05);综合治疗组治疗24周后ADAS-cog量表及ADL量表评分显著低于普通治疗组和对照组(P<0.05),MMSE量表评分显著高于普通治疗组和对照组(P<0.05)。结论:中西医结合治疗阿尔茨海默病疗效显著。