CAJ | 학술논문

目的研究胆碱酯酶抑制剂多奈哌齐对阿尔茨海默病(AD)患者的血小板α和β分泌酶活性的影响.方法选取2007年8月至2010年10月在河南省人民医院神经内科诊治的76例AD患者,随机数字表法分为多奈哌齐治疗组和对照治疗组,每组38例.多奈哌齐治疗组给予多奈哌齐,每晚5 mg口服；对照治疗组给予常规改善脑代谢药物.另设本院同期非痴呆疾病组40例,分别给予相应的治疗.12周后分别测定两组AD患者的AD评定量表认知分量表(ADAS-Cog)、日常生活能力评定量表(ADL)；分别测定非痴呆疾病组和两组AD患者血小板中α和β分泌酶的活性,并用Western印迹检测血小板α分泌酶的产物sAPPα的含量.结果多奈哌齐治疗组降低ADAS-Cog评分(5.3±4.4)分,与对照治疗组的(1.7±1.6)分相比,差异有统计学意义(P＜0.01)；12周后多奈哌齐治组的ADL评分(41±7)分明显低于对照治疗组(48±6)分,差异有统计学意义(P＜0.05)；与治疗前(50±6)分相比,差异有统计学意义(P＜0.05).12周后多奈哌齐治疗组的α分泌酶活性(91％±9％)明显高于对照治疗组(64％±8％,P＜0.01),β分泌酶活性(1 19％±11％)明显低于对照治疗组(178％±17％,P＜0.01)；与治疗前相比差异均有统计学意义(均P＜0.01).对照治疗组血小板sAPPα含量(26％±8％)明显低于非痴呆疾病组(100％±12％) (P ＜0.001),多奈哌齐治疗组12周sAPPα含量(64％±14％)明显高于对照治疗组(P＜0.01).结论多奈哌齐治疗显著提高了AD患者的认知功能和日常生活能力,表现为降低ADAS-Cog和ADL评分；多奈哌齐治疗提高了AD患者血小板α分泌酶活性并降低了β分泌酶的活性；多奈哌齐对AD患者的认知功能的改善可能与其对血小板分泌酶的活性调节有关.
목적 연구담감지매억제제다내고제대아이자해묵병(AD)환자적혈소판α화β분비매활성적영향.방법 선취2007년8월지2010년10월재하남성인민의원신경내과진치적76례AD환자,수궤수자표법분위다내고제치료조화대조치료조,매조38례.다내고제치료조급여다내고제,매만5 mg구복；대조치료조급여상규개선뇌대사약물.령설본원동기비치태질병조40례,분별급여상응적치료.12주후분별측정량조AD환자적AD평정량표인지분량표(ADAS-Cog)、일상생활능력평정량표(ADL)；분별측정비치태질병조화량조AD환자혈소판중α화β분비매적활성,병용Western인적검측혈소판α분비매적산물sAPPα적함량.결과 다내고제치료조강저ADAS-Cog평분(5.3±4.4)분,여대조치료조적(1.7±1.6)분상비,차이유통계학의의(P＜0.01)；12주후다내고제치조적ADL평분(41±7)분명현저우대조치료조(48±6)분,차이유통계학의의(P＜0.05)；여치료전(50±6)분상비,차이유통계학의의(P＜0.05).12주후다내고제치료조적α분비매활성(91％±9％)명현고우대조치료조(64％±8％,P＜0.01),β분비매활성(1 19％±11％)명현저우대조치료조(178％±17％,P＜0.01)；여치료전상비차이균유통계학의의(균P＜0.01).대조치료조혈소판sAPPα함량(26％±8％)명현저우비치태질병조(100％±12％) (P ＜0.001),다내고제치료조12주sAPPα함량(64％±14％)명현고우대조치료조(P＜0.01).결론 다내고제치료현저제고료AD환자적인지공능화일상생활능력,표현위강저ADAS-Cog화ADL평분；다내고제치료제고료AD환자혈소판α분비매활성병강저료β분비매적활성；다내고제대AD환자적인지공능적개선가능여기대혈소판분비매적활성조절유관.
Objective To explore the effects of donepezil on the activities of platelet α and β secretases in Alzheimer's disease (AD) patients.Methods During the period of 2007 -2010,a total of 76AD patients received either regular treatment alone or in combination with donepezil (5 mg/d) for a 12-week period.And their effects on ADAS-Cog (Alzheimer's disease assessment scale-cognitive subscale) total and ADL (activity of daily living) scores were measured.The effects of donepezil on α and β secretase activities and sAPPα (soluble amyloid precursor protein α) secretion in AD patients and non-demented patients were detected by fluorescence and Western blot respectively.Results Mter the donepezil treatment,the ADASCog scores of the treatment group decreased versus the control [ ( 5.3 ± 4.4 ) vs ( 1.7 ± 1.6 ) ].And the differences were statistically significant ( P ＜ 0.01 ).And the ADL scores of the treatment group decreased versus the control [ (41 ±7) vs.(48 ±6) ].And the differences were statistically significant (P ＜0.05).As compared with that of pre-treatment (50 ± 6),the differences were statistically significant (P ＜0.05 ).The activity of α secretase increased markedly while that of β secretase decreased markedly versus the controls [(91％ ±9％) vs (64％ ±8％),P＜0.01; (119％ ±11％) vs (178％ ±17％),P＜0.01].Both had significant statistical differences with those of pre-treatment ( both P ＜ 0.01 ).As compared with the non-demented group ( 100％ ± 12％,P ＜0.001 ),the sAPPα contents of treatment and control groups were (64％ ±14％,P＜0.01) and (26％ ±8％,P＜0.001) respectively.Conclusion The administration of donepezil in AD patients improves cognitive functions and daily activities as indicated by the decreased ADAS-Cog total scores and ADL scores through the increased activity of α secretase and the decreased activity of β secretase.The clinical efficacy of donepezil may be attributed to its pharmacological effects on the regulation of platelet secretase activities.