多奈哌齐治疗阿尔茨海默病对患者血小板α和β分泌酶活性的影响

Effects of donepezil treatment on platelets a and β secretase activities in Alzheimer＇s disease patients

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5mg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d和母分泌酶的活性，并用Western印迹检测血小板d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（1．74-1．6）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），13分泌酶活性（119％±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％4-12％）（P〈0．001），多奈哌齐治疗组12周sAPPoL含量（64％4-14％）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。

Objective To explore the effects of donepezil on the activities of platelet ct andβ secretases in Alzheimer＇s disease （AD） patients. Methods During the period of 2007 - 2010, a total of 76 AD patients received either regular treatment alone or in combination with donepezil （5 rag/d） for aβ-week period. And their effects on ADAS-Cog （Alzheimer＇s disease assessment scale-coguitive subseale） total and ADL （ activity of daily living） scores were measured. The effects of donepezil on ot and β secretase activities and sAPPot （soluble amyloid precursor protein α） secretion in AD patients and non-demented patients were detected by fluorescence and Western blot respectively. Results After the donepezil treatment, the ADAS- Cog 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 ct secretase increased markedly while that of 13 secretase decreased markedly versus the controls [（91%±9%） vs （64% ±8%）, P〈O. O1; （119% ±11%） vs （178%±17%）, P〈0.0O1] . Both had significant statistical differences with those of pre-treatment （ both P 〈 0. O1 ）. As compared with thenon-demented group （100% ± 12%, P 〈0. 001 ）, the sAPPct 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 ct 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.