加减薯蓣丸治疗轻、中度阿尔茨海默病的临床观察

目的:探讨加减薯蓣丸对轻、中度阿尔茨海默病(AD)的临床疗效及可能机制。方法:将96例轻、中度AD患者随机分为治疗组(加减薯蓣丸浓缩汤剂,15 m L/次,1日2次)和对照组(盐酸多奈哌齐片,5 mg/次,睡前1次),每组48例,两组疗程均为12周。于治疗前后对患者进行神经心理测验量表及AD证候要素量表(AD-PES-11)评定。另收集同期认知功能正常的老年健康体检者(48例)为正常组。采用实时荧光定量聚合酶链式反应(Real-time PCR)检测两组治疗前后及正常组血清微小核糖核酸(microRNA,miRNA,miR),包括miR-132,miR-34a,miR-9,let-7i水平。采用Spearman相关系数分析法对神经心理测验量表评分,AD-PES-11积分与miRNAs表达之间进行相关性分析。结果:与本组治疗前比较,两组治疗后简易精神状态量表(MMSE)评分明显升高,日常生活能力量表(ADL)评分显著降低(P0.01);与本组治疗前比较,治疗组治疗后量表总积分、肾虚、脾虚、髓减、痰浊、血瘀积分明显降低(P0.05,P0.01),对照组治疗后脾虚积分明显升高(P0.05);与对照组治疗后比较,治疗组量表总积分、肾虚、脾虚、痰浊、血瘀积分显著降低(P0.01);与正常组比较,两组治疗前血清miR-132,miR-34a,let-7i表达明显升高,miR-9表达显著降低(P0.01);与本组治疗前比较,两组治疗后血清miR-132,miR-34a,let-7i表达明显降低,miR-9表达明显升高(P0.05,P0.01)。相关性分析显示,miR-34a表达水平与肾虚、痰浊积分及总积分呈正相关(P0.01),miR-9表达水平与痰浊积分及总积分呈负相关(P0.05,P0.01)。结论:加减薯蓣丸能有效改善AD患者认知功能和日常生活能力,改善中医肾虚、脾虚、髓减、痰浊、血瘀状态,其机制可能与调节血清miR-132,miR-34a,let-7i,miR-9表达有关。

Clinical Observation of Modified Shuyuwan in Treatment of Mild and Moderate Alzheimer's Disease

Objective: To explore the clinical effect and possible mechanism of modified Shuyuwan in treatment of mild and moderate Alzheimer''s disease(AD). Method: Totally 96 patients with mild and moderate AD were randomly divided into treatment group and control group, with 48 patients in each group. Patients in the treatment group took modified Shuyuwan, 15 mL each time, twice a day, while those in control group took Donepezil tablet, 5 mg/time before bedtime. The treatment course was 12 weeks in both groups. The Mini-mental State Examination (MMSE) scale, Activity of Daily Living (ADL) scale as well as Pattern and Element of Syndrome of Alzheimer''s disease (AD-PES-11) Scale were evaluated before and after treatment. Another 48 cases with normal cognitive function were collected as normal group. The serum microRNA-132 (miR-132), miR-34a, miR-9, and let-7i levels of the 3 groups were measured by Real-time PCR both before and after treatment. Spearman correlation coefficient analysis was used to analyze the correlation between the score of neuropsychological test scales, AD-PES-11 scale and miRNAs levels. Result: As compared with those before treatment, the scores of MMSE were increased significantly after treatment, while the scores of ADL were decreased significantly in both groups (P<0.01). As compared with those before treatment, the scores of AD-PES-11 scale, kidney deficiency, spleen deficiency, medullary decrease, phlegm turbidity and blood stasis were significantly decreased after treatment in treatment group (P<0.05, P<0.01), while in control group, the score of spleen deficiency was increased significantly (P<0.05). As compared with control group, the scores of AD-PES-11 scale, kidney deficiency, spleen deficiency, phlegm and blood stasis were decreased significantly in treatment group after treatment (P<0.01). As compared with normal group, the expression levels of serum miR-132, miR-34a, and let-7i were significantly increased in treatment and control groups before treatment, and the expression of miR-9 was significantly decreased (P<0.01). As compared with those before treatment, the expression levels of serum miR-132, miR-34a, and let-7i were significantly decreased after treatment in the 2 groups, and the expression of miR-9 was significantly increased (P<0.05, P<0.01). Correlation analysis showed that miR-34a expression level was positively correlated with kidney deficiency, phlegm turbidity and total scores (P<0.01); miR-9 expression level was negatively correlated with phlegm turbidity and total scores (P<0.05, P<0.01). Conclusion: Modified Shuyuwan can effectively improve the cognitive function and daily life ability of AD patients, improve the status of kidney deficiency, spleen deficiency, medullary decrease, phlegm turbidity and blood stasis, and its mechanism may be related to regulating the levels of serum miR-132, miR-34a, miR-9 and let-7i.