藏药七十味珍珠丸对阿尔茨海默病患者血清β淀粉样蛋白和炎性细胞因子的影响

摘要

Objective To study the effect of ratanasampil (RNSP) which is Traditional Tibetan Medicine on the levels of serum β-amyloid protein, interleukin and tumor necrosis factor alpha (TNF-α) in patients with mild to moderate Alzheimer's disease (AD). Methods One hundred AD patients were divided into two groups in randomized controlled study, including treatment group (RNSP 1 g/d) and control group (piracetam 2.4 g/d). The treatment lasted 12 weeks. The Mini Mental State Examination (MMSE), Alzheimer' s disease Assessment Scale-cognitive subscale (ADAS-cog) and Activity of Daily Living Scale (ADLs) were taken to evaluate the efficacy. Serum levels of amyloid peptides (Aβ40 and Aβ42 ) were measured by ELISA assay. The radioimmunologic assay was used to determine the serum levels of IL-1β, IL-2, IL-6, IL-8 and TNF-α. Results The scores of MMSE, ADAS-cog and ADL significantly improved at 12 weeks after RNSP treatment (P＜0.01, 0.01, 0.05, respectively), while had no significant changes in piracetam group (P＜0.05).The levels of TNF-α, IL-1β, IL-6 and Aβ42 were significantly lower in RNSP group than in Piracetam group (P＜0.01). There was a decrease trend of the Aβ42/Aβ40 ratio at 12 weeks after RNSP treatment (P＜0. 05, P＜0.01 ). The serum Aβ42 level had strong correlations with TNF-α, IL-1 β and IL-6. There were no significant differences in Aβ40 and IL-8 between RNSP group and piracetam group. No obvious drug side effect happened on the groups. Conclusions The reductions of serum TNF-α, IL-1β and IL-6 levels after RNSP treatment may lead to decrease of Aβ42 production in AD patients. RNSP may decrease the Aβ42/Aβ40 ratio and slow down the progress of AD. It may improve the learning and memory ability in treating patients with mild to moderate AD and is well tolerated and safe.%目的 观察藏药七十味珍珠丸(RNSP)对轻中度阿尔茨海默病(AD)患者血清β淀粉样蛋白(Aβ)和炎性细胞因子的影响,探讨RNSP防治AD可能的机制.方法 100例AD患者分为治疗组和对照组.采用随机、单盲、药物对照的试验设计方法.治疗组RNSP口服1 g/d,对照组吡拉西坦口服2.4 g/d.疗程均为12周.采用简易精神状态量表(MMSE)、阿尔茨海默病评估量表的认知分量表(ADAS-cog)和日常生活活动量表(ADL)问卷调查.受试患者血清(Aβ40和Aβ42)采用酶标免疫吸附法(ELISA)进行测定.白介素(IL)-18、IL2、IL6、IL-8和肿瘤坏死因子(TNF-α)测定采用放射免疫法.结果 RNSP治疗AD患者4周后,MMSE总分、ADAS-cog和ADL有改善,12周时,MMSE评分显著增高,ADAS-cog评分进一步降低,ADL评分中生活自理能力和使用工具能力均有明显改善.而吡拉西坦组的各个项目评分无明显改善(P＞0.05).RNSP能够减少AD患者血清TNF-α、IL-1β、IL-6和Aβ42水平,尤其治疗12周后更加明显.Aβ42/Aβ40比值在治疗12周后有逐渐下降趋势(P＜0.05和P＜0.01).直线相关分析发现,血清中Aβ42水平与TNF-α,IL-1β和IL-6有相关性.RNSP对AD患者血清Aβ40和IL-8的表达无明显的影响.结论 RNSP可能通过下调炎性细胞因子TNF-α,IL-1β和IL-6水平使Aβ42/Aβ40比值下降,减缓了AD的进程,从而改善AD患者认知功能,提高了社会活动和日常生活的能力.