潜阳育阴颗粒早期介入延缓高血压认知障碍患者脑白质病变的临床研究

颜习武; 孟婷; 刘金凤; 洪于兴; 亢姣阳; 刘怀峻; 常诚

doi:10.14148/j.issn.1672-0482.2022.0291

潜阳育阴颗粒早期介入延缓高血压认知障碍患者脑白质病变的临床研究

doi: 10.14148/j.issn.1672-0482.2022.0291

1.
南京中医药大学第一临床医学院, 江苏南京 210023
2.
南京中医药大学附属医院, 江苏南京 210029

基金项目:

国家自然科学基金面上项目 81673759

江苏省中医药科技发展重点项目 RC201901

江苏省社会发展项目 BE2017770

江苏省研究生培养创新工程研究生科研与实践创新计划项目 SJCX21_0772

详细信息

作者简介:
颜习武, 男, 博士研究生, E-mail: yxwssg@126.com

通讯作者:
常诚, 男, 教授, 主任中医师, 主要从事中西医结合诊疗脑血管病和认知障碍的研究, E-mail: chch1967@163.com

中图分类号: R259
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- 被引次数: 0
出版历程
- 收稿日期: 2021-11-15
- 网络出版日期: 2022-04-13
- 发布日期: 2022-04-10

Clinical Study on Early Intervention of Qianyang Yuyin Granules to Slow Progression of Leukoencephalopathy in Hypertensive Patients with Cognitive Impairment

1.
The First School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
2.
The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China

摘要

摘要: 目的观察潜阳育阴颗粒治疗高血压认知障碍患者的临床疗效及对脑白质病变体积的影响。方法采用随机对照、多中心入组，将患者分成治疗组64例、对照组33例、多奈哌齐组34例。对照组予以西医常规基础治疗，治疗组在对照组治疗基础上加服潜阳育阴颗粒，多奈哌齐组在对照组治疗基础上加服多奈哌齐，疗程均为6个月，治疗前后比较3组患者血压、脑白质病变体积、简易精神状态检查表(MMSE)、血管性痴呆评估量表(VaDAS-cog)和中医证候积分变化情况。同时观察3组患者血常规、肝肾功能等安全性指标变化。结果治疗后, 3组患者血压均明显下降(P < 0.01)，组间无明显差异(P>0.05);3组中医证候积分均有下降(P < 0.01), 治疗组优于对照组与多奈哌齐组(P < 0.01);3组患者脑白质病变体积均显著增加(P < 0.01), 治疗组的脑白质病变体积增加少于对照组与多奈哌齐组(P < 0.05);治疗组MMSE评分明显增加(P < 0.01)，优于对照组和多奈哌齐组(P < 0.01);治疗组VaDAS-cog评分显著降低(P < 0.01), 优于对照组(P < 0.01)。治疗期间3组患者均未出现明显不良反应。结论潜阳育阴颗粒能显著改善高血压患者认知功能, 延缓脑白质病变进展, 并具有安全性。
- 高血压 /
- 认知障碍 /
- 潜阳育阴颗粒 /
- 脑白质病变
Abstract: OBJECTIVE To observe the clinical efficacy of Qianyang Yuyin Granules in the treatment of hypertensive patients with cognitive impairment and the effect on their leukoencephalopathy volume. METHODS The patients were randomly divided into 64 cases in the treatment group, 33 cases in the control group, and 34 cases in the donepezil group by randomized controlled, multicenter enrollment. In the control group, the patients were treated with conventional western medicine, while in the treatment group and donepezil group, the patients were separately treated with Qianyang Yuyin Granules and donepezil based on the therapies in the control group. The course of the treatment was 6 months.The changes of blood pressure, leukoencephalopathy volume, Mini-Mental State Examination (MMSE), Vascular Dementia Assessment Scale (VaDAS-cog), as well as traditional Chinese medicine (TCM) syndrome score were compared before and after treatment in the three groups. Besides, the changes of safety indexes such as blood routine examination, liver and kidney function were also observed. RESULTS After treatment, blood pressure was lowered significantly in all three groups (P < 0.01), with no significant differences between each groups(P>0.05). The TCM syndrome score were reduced in all three groups (P < 0.01), while the treatment group showed better results than the control group and the donepezil group did (P < 0.01). The leukoencephalopathy volumes were increased significantly in all three groups (P < 0.01), but the increase of leukoencephalopathy volume in the treatment group was less than that in the control group and the donepezil group (P < 0.05). MMSE scores were increased significantly in the treatment group (P < 0.01), whose results were better than those in the control group and the donepezil group (P < 0.01). VaDAS-cog scores were decreased significantly in the treatment group (P < 0.01), whose results were also better than those in the control group (P < 0.01). In addition, no significant adverse reactions were observed in any of the three groups during the treatment period. CONCLUSION The Qianyang Yuyin Granules can notably improve the cognitive function of hypertensive patients, and can evidently slow their progression of leukoencephalopathy with safety.
- hypertension /
- cognitive impairment /
- Qianyang Yuyin Granules /
- leukoencephalopathy

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图 1 脑白质缺血灶标注图示

注: A.脑白质缺血病灶位置图; B.横断面病灶标记示例图; C.矢状面病灶标记示例图; D.标注完成的脑白质缺血灶3D图

Figure 1. Labeled graph of ischemic foci in the white matter of the brain

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表 1 各单位病例完成情况

Table 1. Case completion in each unit

单位	入组	剔除	脱落	完成试验
江苏省中医院	76	0	7	69
止马营卫生服务中心	8	0	2	6
朝天宫卫生服务中心	7	0	0	7
夫子庙卫生服务中心	8	0	0	8
中华门卫生服务中心	15	0	1	14
溧阳市中医院	17	0	1	16
总计	131	0	11	120

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表 2 3组患者基线资料比较(x±s)

Table 2. Comparison of baseline information of patients in the three groups (x±s)

组别	男	女	年龄/岁	体质量/kg	身高/cm	心率/min^-1	收缩压/mmHg	舒张压/mmHg
治疗组	22	42	66.95±6.55	61.00±11.05	163.07±5.88	76.34±7.01	149.91±10.83	85.08±10.41
对照组	14	19	66.69±4.09	64.42±8.60	164.00±7.94	75.91±6.98	145.64±12.12	85.01±9.93
多奈哌齐组	9	25	68.10±7.37	61.85±10.85	161.70±7.55	76.65±6.69	144.44±13.74	86.18±9.72

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表 3 中医证候积分评分标准

Table 3. Evaluation standard of TCM syndrome score

症状		0级	1级	2级	3级
主症	记忆减退	0分: 无症状	2分: 轻微减退, 易忘近事	4分: 介于两者之间	6分: 记忆减退, 不识熟人
	头晕头痛	0分: 无症状	2分: 偶尔头晕头痛	4分: 介于两者之间	6分: 经常头晕头痛
	腰膝酸软	0分: 无症状	2分: 晨起腰酸, 捶打可止	4分: 介于两者之间	6分: 腰膝酸软, 不能缓解
次症	口干口苦	0分: 无症状	1分: 晨起口干口苦	2分: 介于两者之间	3分: 口干口苦持续不解
	心悸失眠	0分: 无症状	1分: 活动后心悸, 睡眠差	2分: 介于两者之间	3分: 静息心悸, 难以入眠
	便秘	0分: 无症状	1分: 大便3日一行	2分: 介于两者之间	3分: 大便7日以上一行
	耳鸣	0分: 无症状	1分: 轻微耳鸣	2分: 介于两者之间	3分: 耳鸣不止, 听力减退

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表 4 3组患者治疗前后血压比较(x±s, mmHg)

Table 4. Comparison of blood pressure of patients in the three groups before and after treatment (x±s, mmHg)

组别	时间	收缩压	舒张压
治疗组	治疗前	149.91±10.83	85.08±10.41
(n=64)	治疗后	138.38±9.90^**	84.02±7.85^**
对照组	治疗前	145.64±12.12	85.01±9.93
(n=33)	治疗后	135.24±11.92^**	83.12±5.31^**
多奈哌齐组	治疗前	144.44±13.74	86.18±9.72
(n=34)	治疗后	137.76±12.31^**	83.11±6.78^**
注: 组内比较, ^{* *}P < 0.01。

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表 5 3组患者治疗前后MMSE、VaDAS-cog比较(x±s)

Table 5. Comparison of MMSE and VaDAS-cog before and after treatment in the three groups (x±s)

组别	时间	MMSE	VaDAS-cog
治疗组	治疗前	25.41±1.11	13.43±7.41
(n=64)	治疗后	28.03±1.00^**##△△	9.92±6.22^**##
对照组	治疗前	25.62±0.59	14.27±6.29
(n=33)	治疗后	24.75±0.68	16.00±6.83
多奈哌齐组	治疗前	24.08±2.19	15.05±7.76
(n=34)	治疗后	25.08±1.82	13.09±7.79
注: 组内比较, ^{* *}P < 0.01;与对照组比较, ^##P < 0.01;与多奈哌齐组比较, ^△△P < 0.01。

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表 6 3组患者治疗前后脑白质病变体积变化比较[M(IQR), cm³]

Table 6. Comparison of the changes in leukoencephalopathy volumes before and after treatment in the three groups [M(IQR), cm³]

组别	例数	治疗前	治疗后	治疗后脑白质病变体积增加
治疗组	64	14.46 (16.82)	18.19 (16.76)^**	2.08 (2.98)^#△
对照组	33	12.69 (9.94)	18.20 (12.85)^**	3.20 (4.21)
多奈哌齐组	34	10.09 (11.20)	13.57 (11.58)^**	2.29 (2.54)
注: 组内比较, ^{* *}P < 0.01;与对照组比较, ^#P < 0.05;与多奈哌齐组比较, ^△P < 0.05。

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表 7 3组患者治疗前后中医证候积分比较(x±s)

Table 7. Comparison of TCM syndrome scores before and after treatment in the three groups (x±s)

组别	时间	记忆减退	头晕头痛	腰膝酸软	口干口苦
治疗组	治疗前	2.56±0.91	3.56±1.21	1.61±1.77	1.44±0.77
(n=64)	治疗后	0.60±0.87^**##△△	1.75±1.04^**	1.10±0.75	0.53±0.87^**
对照组	治疗前	2.72±0.98	4.12±1.09	2.65±1.81	1.09±0.97
(n=33)	治疗后	2.35±0.77	1.69±1.25^**	1.49±1.12^**	0.53±0.93^**
多奈哌齐组	治疗前	2.59±0.92	3.88±1.22	1.63±1.83	1.72±0.94
(n=34)	治疗后	1.39±0.93^**##	1.94±1.27^**	1.13±0.91	0.61±1.03^**

组别	时间	心悸失眠	便秘	耳鸣	总积分
治疗组	治疗前	2.55±0.69	1.15±1.01	0.66±0.83	13.11±3.66
(n=64)	治疗后	1.55±1.11^**	0.35±0.53^**	0.12±0.45^**	5.45±2.40^**##△△
对照组	治疗前	1.59±1.31	1.26±0.83	0.67±1.11	13.91±3.59
(n=33)	治疗后	1.32±1.09	0.50±0.75^**	0.13±0.17^**	7.32±2.72^**
多奈哌齐组	治疗前	2.15±0.87	1.12±0.86	0.65±0.92	13.94±3.89
(n=34)	治疗后	1.55±1.12^*	0.42±0.71^**	0.18±0.63^**	6.87±2.10^**##
注: 组内比较, ^P < 0.05, ^{ *}P < 0.01;与对照组比较, ^##P < 0.01;与多奈哌齐组比较, ^△△P < 0.01。

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表 8 3组患者治疗前后安全性指标比较(x±s)

Table 8. Comparison of safety indexes before and after treatment in the three groups (x±s)

组别	时间	Hb/(g·L^-1)	PLT/(×10⁹·L^-1)	ALT/(U·L^-1)	AST/(U·L^-1)	BUN/(mmol·L^-1)	Cr/(μmol·L^-1)
治疗组	治疗前	128.83±17.63	195.28±47.85	26.61±9.39	30.31±8.36	6.43±3.28	59.33±12.71
(n=64)	治疗后	129.03±12.62	198.05±45.08	25.14±8.67	28.54±9.04	6.89±3.77	63.14±18.17
对照组	治疗前	128.20±16.63	195.73±43.62	26.46±10.58	22.99±7.82	5.80±2.38	58.43±13.24
(n=33)	治疗后	129.16±12.55	197.67±46.45	29.38±12.63	23.76±10.10	5.72±2.53	58.36±15.37
多奈哌齐组	治疗前	131.22±14.52	196.53±51.11	31.32±7.86	26.33±9.62	4.96±3.22	65.62±16.22
(n=34)	治疗后	130.78±15.37	192.77±56.97	27.84±10.35	27.81±11.31	5.62±2.74	61.32±17.27
注：Hb.血红蛋白; PLT.血小板; ALT.谷丙转氨酶; AST.谷草转氨酶; BUN.尿素氮; Cr.肌酐。

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