Article(id=1322927281815040810, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322926985957221241, articleNumber=null, orderNo=null, doi=10.13193/j.issn.1673-7717.2025.11.040, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=null, receivedDateStr=null, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1793340042785, onlineDateStr=2026-10-30, pubDate=1762704000000, pubDateStr=2025-11-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793340042785, onlineIssueDateStr=2026-10-30, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793340042785, creator=13701087609, updateTime=1793340042785, updator=13701087609, issue=Issue{id=1322926985957221241, tenantId=1146029695717560320, journalId=1255847919539208197, year='2025', volume='43', issue='11', pageStart='1', pageEnd='258', issueExtLink='null', onlineDate='null', pubDate='1762704000000', pubDateStr='2025-11-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1793339972247, creator='13701087609', updateTime=1793340743335, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1322930220201804556, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322926985957221241, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1322930220201804557, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322926985957221241, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=200, endPage=203, ext={EN=ArticleExt(id=1322927282238665515, articleId=1322927281815040810, tenantId=1146029695717560320, journalId=1255847919539208197, language=EN, title=Clinical Efficacy and Safety Observation on Treatment of Insomnia of Heart-Kidney Yang Deficiency Type by Combining Fuzi Decoction(附子汤)and Guizhi Gancao Longgu Muli Decoction(桂枝甘草龙骨牡蛎汤), columnId=1256183365644968140, journalTitle=Chinese Archives of Traditional Chinese Medicine, columnName=Platform of Provincial Project, runingTitle=null, highlight=null, articleAbstract=
Objective

To observe the clinical efficacy and safety of the treatment of insomnia of heart-kidney Yang deficiency type with Fuzi Decoction(附子汤)combined with Guizhi Gancao Longgu Muli Decoction(桂枝甘草龙骨牡蛎汤).

Methods

A total of 114 patients with insomnia due to deficiency of heart and kidney yang were enrolled from January 2022 to December 2023. Simple randomization was performed using a random number table. The Western medicine group(n=57)received zopiclone treatment,while the pattern differentiation group(n=57)received Fuzi Tang combined with Guizhi Gancao Longgu Muli Tang. Both groups underwent continuous treatment for 4 weeks. The following parameters were assessed:Hamilton Anxiety Scale(HAMA)scores,5-hydroxytryptamine(5-HT),glutamate,gamma-aminobutyric acid(GABA),melatonin,Pittsburgh Sleep Quality Index(PSQI)scores,sleep architecture,TCM syndrome scores,and Hamilton Depression Scale(HAMD)scores. Efficacy and safety were statistically analyzed between groups.

Results

Following treatment,both groups exhibited reduced HAMD scores,PSQI scores,TCM syndrome scores,and HAMA scores compared to pre-treatment levels,with the patterndifferentiation group showing lower scores than the Western medicine group(P<0.05). The pattern-differentiation group achieved a total effective rate of 92.98% (53/57 cases),surpassing the Western medicine group's rate of 78.95% (45/57 cases)(P<0.05). Post-treatment levels of serotonin and glutamate decreased in both groups compared to pre-treatment levels,with the pattern-differentiation group showing a greater reduction than the Western medicine group(P<0.05). Post-treatment levels of gamma-aminobutyric acid(GABA)and melatonin increased in both groups compared to pre-treatment levels,with the pattern-differentiation group showing a greater increase than the Western medicine group(P<0.05). After treatment,both groups showed reduced sleep latency(SOL)and wake-up time(WASO)compared to pre-treatment levels,with the pattern-differentiation group exhibiting a greater reduction than the Western medicine group(P<0.05). Following treatment,both groups exhibited increased total sleep time(TST)and sleep efficiency(SE)compared to pre-treatment levels,with the pattern-differentiation group showing greater improvement than the Western medicine group(P<0.05). The overall adverse reaction rate in the pattern-differentiation group was 5.26% (3/57 cases),compared to 7.02% (4/57 cases)in the Western medicine group,with no statistically significant difference(P>0.05).

Conclusion

The treatment of heart-kidney Yang deficiency type of insomnia by Fuzi Decoction combined with Guizhi Gancao Longgu Muli Decoction can regulate the neurotransmitters,improve the sleep structure and enhance the clinical efficacy.

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目的

观察附子汤合桂枝甘草龙骨牡蛎汤治疗心肾阳虚型失眠的临床疗效与安全性。

方法

选取2022年1月—2023年12月收治的心肾阳虚型失眠患者114例,采用随机数字表法进行简单随机分组。西药组57例给予右佐匹克隆治疗,辨证组57例给予附子汤合桂枝甘草龙骨牡蛎汤治疗,连续用药4周。评估两组汉密尔顿焦虑量表(Hamilton anxiety scale,HAMA)评分、5-羟色胺、谷氨酸、γ-氨基丁酸、褪黑素、匹兹堡睡眠质量指数(Pittsburgh sleep quality index,PSQI)评分、睡眠结构、中医证候评分和汉密尔顿抑郁量表(Hamilton depression scale,HAMD)评分变化,统计两组疗效和安全性。

结果

治疗后两组HAMD评分、PSQI评分、中医证候评分、HAMA评分均较治疗前降低,辨证组较西药组更低(P<0.05)。辨证组总有效率为92.98%(53/57),高于西药组的78.95%(45/57)(P<0.05)。治疗后两组5-羟色胺、谷氨酸均较治疗前降低,辨证组较西药组更低(P<0.05);治疗后两组γ-氨基丁酸、褪黑素均较治疗前升高,辨证组较西药组更高(P<0.05)。治疗后两组睡眠潜伏期(Sleep latency,SOL)、觉醒时间(Wake-up time,WASO)均较治疗前降低,辨证组较西药组更低(P<0.05);治疗后两组总睡眠时间(Total sleep time,TST)、睡眠效率(Sleep efficiency,SE)均较治疗前升高,辨证组较西药组更高(P<0.05)。辨证组总不良反应率5.26%(3/57),与西药组7.02%(4/57)比较,差异无统计学意义(P>0.05)。

结论

附子汤合桂枝甘草龙骨牡蛎汤治疗心肾阳虚型失眠可调节神经递质,改善睡眠结构,提高临床疗效。

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朱晓军(1979-),女,福建永安人,副主任中医师,硕士,研究方向:中医内科。

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refAbstract=null), Reference(id=1322927296209892226, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322927281815040810, doi=null, pmid=null, pmcid=null, year=2022, volume=38, issue=7, pageStart=53, pageEnd=55, url=null, language=null, rfNumber=[28], rfOrder=27, authorNames=姜新媛, 张海啸, journalName=中国社区医师, refType=null, unstructuredReference=姜新媛,张海啸. 加味桂枝甘草龙骨牡蛎汤联合艾司唑仑片治疗心胆气虚型失眠的临床研究[J]. 中国社区医师,2022,38(7):53-55., articleTitle=加味桂枝甘草龙骨牡蛎汤联合艾司唑仑片治疗心胆气虚型失眠的临床研究, refAbstract=null), Reference(id=1322927296268612483, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322927281815040810, doi=null, pmid=null, pmcid=null, year=2019, volume=43, issue=8, pageStart=817, pageEnd=819, url=null, language=null, rfNumber=[29], rfOrder=28, authorNames=杨营, 丁泽琳, 王海霞, journalName=浙江中医药大学学报, refType=null, unstructuredReference=杨营,丁泽琳,王海霞. 从“阳虚阴不内守”论桂枝加龙骨牡蛎汤的临床应用[J]. 浙江中医药大学学报,2019,43(8):817-819., articleTitle=从“阳虚阴不内守”论桂枝加龙骨牡蛎汤的临床应用, refAbstract=null), 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组别例数PSQI评分中医证候评分HAMD评分HAMA评分
治疗前治疗后治疗前治疗后治疗前治疗后治疗前治疗后
西药组5714.12±2.989.25±1.45*24.85±2.0412.74±1.56*12.94±2.218.87±1.68*11.76±1.827.96±1.27*
辨证组5713.97±3.027.07±1.88*24.37±2.158.56±1.44*13.01±2.146.24±1.33*11.84±1.795.34±1.03*
t值0.2676.9321.22314.8650.1729.2670.23712.097
P值0.7900.0000.2240.0000.8640.0000.8130.000
), ArticleFig(id=1322927290971206491, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322927281815040810, language=CN, label=表1, caption=

两组心肾阳虚型失眠患者相关评分比较(±s)

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组别例数PSQI评分中医证候评分HAMD评分HAMA评分
治疗前治疗后治疗前治疗后治疗前治疗后治疗前治疗后
西药组5714.12±2.989.25±1.45*24.85±2.0412.74±1.56*12.94±2.218.87±1.68*11.76±1.827.96±1.27*
辨证组5713.97±3.027.07±1.88*24.37±2.158.56±1.44*13.01±2.146.24±1.33*11.84±1.795.34±1.03*
t值0.2676.9321.22314.8650.1729.2670.23712.097
P值0.7900.0000.2240.0000.8640.0000.8130.000
), ArticleFig(id=1322927291042509660, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322927281815040810, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别例数临床治愈显效有效无效总有效
西药组5715(26.32)17(29.82)13(22.81)12(21.05)45(78.95)
辨证组5726(45.61)18(31.58)9(15.79)4(7.02)53(92.98)
χ2值4.653
P值0.031
), ArticleFig(id=1322927291134784349, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322927281815040810, language=CN, label=表2, caption=

两组心肾阳虚型失眠患者疗效比较

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组别例数临床治愈显效有效无效总有效
西药组5715(26.32)17(29.82)13(22.81)12(21.05)45(78.95)
辨证组5726(45.61)18(31.58)9(15.79)4(7.02)53(92.98)
χ2值4.653
P值0.031
), ArticleFig(id=1322927291310945118, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322927281815040810, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别例数5-羟色胺/(μmol/L)谷氨酸/(μmol/L)γ-氨基丁酸/(mg/mL)褪黑素/(pg/mL)
治疗前治疗后治疗前治疗后治疗前治疗后治疗前治疗后
西药组570.55±0.210.27±0.10*71.43±21.4351.14±15.63*6.58±2.119.05±1.76*40.14±6.7747.98±5.78*
辨证组570.54±0.230.21±0.08*70.54±24.3644.72±12.57*6.47±2.0811.41±2.08*39.75±7.0556.71±6.82*
t值0.2423.5370.2072.4170.2806.5390.3017.373
P值0.8090.0010.8360.0170.7800.0000.7640.000
), ArticleFig(id=1322927291407414112, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322927281815040810, language=CN, label=表3, caption=

两组心肾阳虚型失眠患者5-羟色胺、谷氨酸、γ-氨基丁酸、褪黑素比较(±s)

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组别例数5-羟色胺/(μmol/L)谷氨酸/(μmol/L)γ-氨基丁酸/(mg/mL)褪黑素/(pg/mL)
治疗前治疗后治疗前治疗后治疗前治疗后治疗前治疗后
西药组570.55±0.210.27±0.10*71.43±21.4351.14±15.63*6.58±2.119.05±1.76*40.14±6.7747.98±5.78*
辨证组570.54±0.230.21±0.08*70.54±24.3644.72±12.57*6.47±2.0811.41±2.08*39.75±7.0556.71±6.82*
t值0.2423.5370.2072.4170.2806.5390.3017.373
P值0.8090.0010.8360.0170.7800.0000.7640.000
), ArticleFig(id=1322927291491300193, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322927281815040810, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别例数TST/(min)SOL/(min)WASO/(min)SE/(%)
治疗前治疗后治疗前治疗后治疗前治疗后治疗前治疗后
西药组57352.23±41.58405.52±43.36*38.95±15.6324.25±10.34*75.56±18.4126.86±9.11*75.53±12.6579.45±14.47*
辨证组57348.96±45.17434.74±48.01*39.11±13.7420.08±8.17*74.19±20.2720.01±7.74*74.91±14.0888.52±16.35*
t值0.4023.4100.0582.3890.3784.3260.2473.136
P值0.6880.0010.9540.0190.7060.0000.8050.002
), ArticleFig(id=1322927291818455906, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322927281815040810, language=CN, label=表4, caption=

两组心肾阳虚型失眠患者睡眠结构比较

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组别例数TST/(min)SOL/(min)WASO/(min)SE/(%)
治疗前治疗后治疗前治疗后治疗前治疗后治疗前治疗后
西药组57352.23±41.58405.52±43.36*38.95±15.6324.25±10.34*75.56±18.4126.86±9.11*75.53±12.6579.45±14.47*
辨证组57348.96±45.17434.74±48.01*39.11±13.7420.08±8.17*74.19±20.2720.01±7.74*74.91±14.0888.52±16.35*
t值0.4023.4100.0582.3890.3784.3260.2473.136
P值0.6880.0010.9540.0190.7060.0000.8050.002
), ArticleFig(id=1322927291914924899, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322927281815040810, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别例数胃肠道不适口苦乏力嗜睡总不良反应
西药组570(0.00)1(17.54)1(17.54)2(3.51)4(7.02)
辨证组572(3.51)1(17.54)0(0.00)0(0.00)3(5.26)
矫正统计值0.000
P值1.000
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两组心肾阳虚型失眠患者安全性比较

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组别例数胃肠道不适口苦乏力嗜睡总不良反应
西药组570(0.00)1(17.54)1(17.54)2(3.51)4(7.02)
辨证组572(3.51)1(17.54)0(0.00)0(0.00)3(5.26)
矫正统计值0.000
P值1.000
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附子汤合桂枝甘草龙骨牡蛎汤治疗心肾阳虚型失眠临床疗效观察
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朱晓军 , 曾华龙 , 朱淑清 , 郑碧榕
中华中医药学刊 | 省级项目平台 2025,43(11): 200-203
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中华中医药学刊 |省级项目平台 2025 , 43 (11) : 200 -203
附子汤合桂枝甘草龙骨牡蛎汤治疗心肾阳虚型失眠临床疗效观察
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朱晓军, 曾华龙, 朱淑清, 郑碧榕
作者信息
  • 三明市第一医院,福建 三明 365000
作者简介:

朱晓军(1979-),女,福建永安人,副主任中医师,硕士,研究方向:中医内科。

Clinical Efficacy and Safety Observation on Treatment of Insomnia of Heart-Kidney Yang Deficiency Type by Combining Fuzi Decoction(附子汤)and Guizhi Gancao Longgu Muli Decoction(桂枝甘草龙骨牡蛎汤)
Xiaojun ZHU, Hualong ZENG, Shuqing ZHU, Birong ZHENG
Affiliations
  • Traditional Chinese Medicine Department,Sanming First Hospital,Sanming 365000,Fujian,China
出版时间: 2025-11-10 doi: 10.13193/j.issn.1673-7717.2025.11.040
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目的

观察附子汤合桂枝甘草龙骨牡蛎汤治疗心肾阳虚型失眠的临床疗效与安全性。

方法

选取2022年1月—2023年12月收治的心肾阳虚型失眠患者114例,采用随机数字表法进行简单随机分组。西药组57例给予右佐匹克隆治疗,辨证组57例给予附子汤合桂枝甘草龙骨牡蛎汤治疗,连续用药4周。评估两组汉密尔顿焦虑量表(Hamilton anxiety scale,HAMA)评分、5-羟色胺、谷氨酸、γ-氨基丁酸、褪黑素、匹兹堡睡眠质量指数(Pittsburgh sleep quality index,PSQI)评分、睡眠结构、中医证候评分和汉密尔顿抑郁量表(Hamilton depression scale,HAMD)评分变化,统计两组疗效和安全性。

结果

治疗后两组HAMD评分、PSQI评分、中医证候评分、HAMA评分均较治疗前降低,辨证组较西药组更低(P<0.05)。辨证组总有效率为92.98%(53/57),高于西药组的78.95%(45/57)(P<0.05)。治疗后两组5-羟色胺、谷氨酸均较治疗前降低,辨证组较西药组更低(P<0.05);治疗后两组γ-氨基丁酸、褪黑素均较治疗前升高,辨证组较西药组更高(P<0.05)。治疗后两组睡眠潜伏期(Sleep latency,SOL)、觉醒时间(Wake-up time,WASO)均较治疗前降低,辨证组较西药组更低(P<0.05);治疗后两组总睡眠时间(Total sleep time,TST)、睡眠效率(Sleep efficiency,SE)均较治疗前升高,辨证组较西药组更高(P<0.05)。辨证组总不良反应率5.26%(3/57),与西药组7.02%(4/57)比较,差异无统计学意义(P>0.05)。

结论

附子汤合桂枝甘草龙骨牡蛎汤治疗心肾阳虚型失眠可调节神经递质,改善睡眠结构,提高临床疗效。

附子汤合桂枝甘草龙骨牡蛎汤  /  心肾阳虚型  /  失眠  /  神经递质  /  睡眠结构  /  疗效
Objective

To observe the clinical efficacy and safety of the treatment of insomnia of heart-kidney Yang deficiency type with Fuzi Decoction(附子汤)combined with Guizhi Gancao Longgu Muli Decoction(桂枝甘草龙骨牡蛎汤).

Methods

A total of 114 patients with insomnia due to deficiency of heart and kidney yang were enrolled from January 2022 to December 2023. Simple randomization was performed using a random number table. The Western medicine group(n=57)received zopiclone treatment,while the pattern differentiation group(n=57)received Fuzi Tang combined with Guizhi Gancao Longgu Muli Tang. Both groups underwent continuous treatment for 4 weeks. The following parameters were assessed:Hamilton Anxiety Scale(HAMA)scores,5-hydroxytryptamine(5-HT),glutamate,gamma-aminobutyric acid(GABA),melatonin,Pittsburgh Sleep Quality Index(PSQI)scores,sleep architecture,TCM syndrome scores,and Hamilton Depression Scale(HAMD)scores. Efficacy and safety were statistically analyzed between groups.

Results

Following treatment,both groups exhibited reduced HAMD scores,PSQI scores,TCM syndrome scores,and HAMA scores compared to pre-treatment levels,with the patterndifferentiation group showing lower scores than the Western medicine group(P<0.05). The pattern-differentiation group achieved a total effective rate of 92.98% (53/57 cases),surpassing the Western medicine group's rate of 78.95% (45/57 cases)(P<0.05). Post-treatment levels of serotonin and glutamate decreased in both groups compared to pre-treatment levels,with the pattern-differentiation group showing a greater reduction than the Western medicine group(P<0.05). Post-treatment levels of gamma-aminobutyric acid(GABA)and melatonin increased in both groups compared to pre-treatment levels,with the pattern-differentiation group showing a greater increase than the Western medicine group(P<0.05). After treatment,both groups showed reduced sleep latency(SOL)and wake-up time(WASO)compared to pre-treatment levels,with the pattern-differentiation group exhibiting a greater reduction than the Western medicine group(P<0.05). Following treatment,both groups exhibited increased total sleep time(TST)and sleep efficiency(SE)compared to pre-treatment levels,with the pattern-differentiation group showing greater improvement than the Western medicine group(P<0.05). The overall adverse reaction rate in the pattern-differentiation group was 5.26% (3/57 cases),compared to 7.02% (4/57 cases)in the Western medicine group,with no statistically significant difference(P>0.05).

Conclusion

The treatment of heart-kidney Yang deficiency type of insomnia by Fuzi Decoction combined with Guizhi Gancao Longgu Muli Decoction can regulate the neurotransmitters,improve the sleep structure and enhance the clinical efficacy.

Fuzi Decoction(附子汤)combined with Guizhi Gancao Longgu Muli Decoction(桂枝甘草龙骨牡蛎汤)  /  heart and kidney Yang deficiency type  /  insomnia  /  neurotransmitters  /  sleep structure  /  therapeutic efficacy
朱晓军, 曾华龙, 朱淑清, 郑碧榕. 附子汤合桂枝甘草龙骨牡蛎汤治疗心肾阳虚型失眠临床疗效观察. 中华中医药学刊, 2025 , 43 (11) : 200 -203 . DOI: 10.13193/j.issn.1673-7717.2025.11.040
Xiaojun ZHU, Hualong ZENG, Shuqing ZHU, Birong ZHENG. Clinical Efficacy and Safety Observation on Treatment of Insomnia of Heart-Kidney Yang Deficiency Type by Combining Fuzi Decoction(附子汤)and Guizhi Gancao Longgu Muli Decoction(桂枝甘草龙骨牡蛎汤)[J]. Chinese Archives of Traditional Chinese Medicine, 2025 , 43 (11) : 200 -203 . DOI: 10.13193/j.issn.1673-7717.2025.11.040
失眠症是临床常见的睡眠问题,临床表现为入睡困难、多梦、易醒、早醒、醒后难以再次入睡、醒后疲劳乏力、头晕不适等。有调查发现,30%~40%的成人曾出现失眠,其中约9%~15%会演变成慢性失眠[1]。睡眠质量的下降可增加心脑血管疾病风险,诱发负性情绪。目前西医临床一般采用短、中效苯二氮卓类受体激动剂治疗,其短期疗效确切,可有效缓解失眠相关症状,但长期服用可引起依赖性[2]。中医学理论将失眠症归纳于“不寐”“卧不安”等范畴,情志失常、饮食不节、外邪侵袭、劳逸失度、年老体衰等均可导致气血失调、营卫失和而致不寐。心肾阳虚是其较为常见的证型。治则以扶阳补肾为法[3]。附子汤出自《伤寒论》,善复阳补肾,散寒除湿[4]。桂枝甘草龙骨牡蛎汤亦出自《伤寒论》,善温阳、安神定悸[5]。本研究将此二经方化裁,观察附子汤合桂枝甘草龙骨牡蛎汤治疗心肾阳虚型失眠的临床疗效与安全性。
失眠症参考《中国精神障碍分类与诊断标准》[6]中标准:临床以失眠为主要症状,因过度在意睡眠状态失眠已引起社会功能受损,发作频率≥3次/周,同时排除继发性失眠。中医参考《中医病证诊断疗效标准》[7]中心肾阳虚型标准。
纳入标准:(1)符合失眠症标准;(2)1周内未接受中西医相关治疗;(3)年龄18~75周岁;(4)匹兹堡睡眠质量指数(Pittsburgh sleep quality index,PSQI)评分>7分;(5)中医属于心肾阳虚型标准;(6)入组前同意加入本研究。
排除标准:(1)合并严重器质性疾病;(2)酗酒、滥用药物或存在药物依赖性;(3)孕妇或哺乳期患者;(4)对右佐匹克隆或附子汤合桂枝甘草龙骨牡蛎汤过敏;(5)合并精神疾病。
选取2022年1月—2023年12月收治的114例心肾阳虚型失眠患者,采用随机数字表法进行简单随机分组。西药组57例给予右佐匹克隆治疗,男25例,女32例;年龄27~75岁,平均(56.77±9.36)岁;病程2~19个月,平均(8.47±4.55)个月;基础疾病:高血压病14例,冠心病27例,糖尿病11例。辨证组57例给予附子汤合桂枝甘草龙骨牡蛎汤治疗,男27例,女30例;年龄25~75岁,平均(57.96±9.01)岁;病程2~21个月,平均(8.52±4.88)个月;基础疾病:高血压病10例,冠心病28例,糖尿病13例。两组病程、基础疾病等比较,差异均无统计学意义(P>0.05)。本研究经医院伦理委员会批准。
西药组给予右佐匹克隆片(成都康弘生物科技有限公司,规格:1mg,国药准字H20100074)治疗,每晚临睡前单次口服右佐匹克隆3 mg,60岁以上减量为2 mg。
辨证组给予附子汤合桂枝甘草龙骨牡蛎汤治疗,组方:党参30 g,茯神10 g,白芍15 g,炮附子6 g,桂枝15 g,炙甘草6 g,生龙骨(先煎)30 g,生牡蛎(先煎)30 g,砂仁(后下)9g。伴湿盛者加茯苓15 g、炒白术15 g;伴气滞者加紫苏叶9 g;伴血瘀者加当归15 g,丹参15 g;伴烦躁者加柴胡9 g,炒栀子9 g。畏冷、疲乏、夜尿甚者加巴戟天15 g、淫羊藿15 g。上药1剂/d,水煎取汁400 mL,早晚各温服200 mL。两组连续用药4周。
PSQI评分[8]:由19个自评与5个他评条目构成,涵盖7个维度,总分21分,分值与患者失眠程度成正比。中医证候评分[7]:包括入眠困难、神疲倦怠、畏寒怕冷3项主症,以患者严重程度量化评分,共分为4个等级,对应0、2、4和6分。其中手足不温、心悸、面色白、小便清长、夜尿频多5项次症,共分为4个等级,对应0、1、2和3分。舌脉正常不计分,异常计1分。汉密尔顿焦虑量表(Hamilton anxiety scale,HAMA)和汉密尔顿抑郁量表(Hamilton depression scale,HAMD)评分[9]评估不良情绪,其中前者14条,分值0~56分,后者17条,分值0~68分,两项均为分值越高不良情绪越多。
临床治愈:入睡时间≤30 min,夜间睡眠≥8 h,早醒、疲劳、记忆力减退等失眠引发症状消失;显效:入睡时间≤30 min,夜间睡眠6~8 h,失眠引发症状显著减轻;好转:入睡时间≤30 min,夜间睡眠4~6 h,失眠引发症状有所减轻;无效:入睡和夜间睡眠时间均未改善,甚至加重。
于治疗前、治疗4周后抽取两组患者外周血5 mL左右,室温放置0.5 h后离心处理,转速3000 r/min。离心时间10 min,离心半径12.5 cm。吸取血清采用美国Waters公司ACQUITY UPLC超高效液相色谱-串联质谱联用仪检测5-羟色胺、谷氨酸、γ-氨基丁酸、褪黑素。
于治疗前、治疗4周后采用美国飞利浦伟康公司Alice 5型多导睡眠监测系统对两组患者进行多导睡眠监测,记录睡眠潜伏期(Sleep latency,SOL)、觉醒时间(Wakeup time,WASO)、总睡眠时间(Total sleep time,TST)、睡眠效率(Sleep efficiency,SE)。
记录两组胃肠道不适、口苦、乏力、嗜睡的发生率。
数据采用SPSS26.0处理,计数资料用例(%)描述,比较用χ2检验或连续矫正检验,ShaPiro-Wilk检验已证实5-羟色胺、谷氨酸、褪黑素等计量指标均服从正态分布以()表示,比较用t检验,P<0.05表示差异有统计学意义。
治疗后两组HAMD评分、PSQI评分、中医证候评分、HAMA评分均较治疗前降低,辨证组较西药组更低(P<0.05)。见表1。
辨证组总有效率为92.98%,高于西药组的78.95%,差异有统计学意义(P<0.05)。见表2。
治疗后两组5-羟色胺、谷氨酸均较治疗前降低,辨证组较西药组更低(P<0.05);治疗后两组γ-氨基丁酸、褪黑素均较治疗前升高,辨证组较西药组更高(P<0.05)。见表3。
治疗后两组TST、SE均较治疗前升高,辨证组较西药组更高(P<0.05);治疗后两组SOL、WASO均较治疗前降低,辨证组较西药组更低(P<0.05)。见表4。
辨证组总不良反应率5.26%,与西药组7.02%比较,差异无统计学意义(P>0.05)。见表5。
失眠的发生机制比较复杂,已有的研究认为,神经递质分泌紊乱、下丘脑-垂体-肾上腺轴功能紊乱、褪黑素及其受体作用紊乱、细胞因子异常分泌、精神心理因素等均可能参与失眠过程[10]。失眠好发于老年人、女性、有家族史、合并焦虑、性格敏感、慢性疾病患者等人群[11]。右佐匹克隆是临床治疗失眠的常用药物,属于非苯二氮卓类药物,可作用于与苯二氮卓受体偶联的GABA受体复合物而发挥催眠作用。但其可引起嗜睡、头晕头痛、胃肠道不适等不良反应,并引起依赖性[12]。
中医学理论认为,心为神之舍,为阳中之阳,心阳不足则失于温煦,神明不能内守于心,神不安其舍,使卧而不寐。肾中阴阳为一身之根,肾阳不足则心、肝、脾三脏失于温养,脏腑失调则睡眠不安。肾阳虚弱无法启真阴上济于心,导致心肾不交而致失眠。《证治要诀》有云:“年高人阳衰不寐”,指出老年人由于阳虚而更易发生失眠[13]。附子汤合桂枝甘草龙骨牡蛎汤中附子、党参共为君药,功擅温补心肾阳气,附子还可引浮阳入阴分;桂枝温经散寒、助阳化气为臣药。佐以茯神宁心安神、利水消肿;白芍敛阴平肝,有助于阴血回归心脉以养心神;生龙骨、生牡蛎摄纳浮越之阳、潜镇安神;砂仁有助于理气和胃,与附子配伍,有助于摄纳浮阳。炙甘草益气复脉,兼为使药,调和药性。伴湿盛者加茯苓、炒白术以健脾祛湿;伴气滞者加紫苏叶以理气行滞;伴血瘀者加当归、丹参以活血化瘀;伴烦躁者加柴炒栀子以安神解郁。畏冷、疲乏、夜尿甚者加巴戟天、淫羊藿以固精缩尿。诸药共奏扶阳补肾、安神助眠之功效[14-15]。
本研究发现,治疗后两组PSQI评分、中医证候评分、HAMD评分、HAMA评分均降低,辨证组较西药组更低。辨证组总有效率高于西药组。这一结果提示,附子汤合桂枝甘草龙骨牡蛎汤治疗心肾阳虚型失眠具有更好的临床疗效,有助于改善睡眠质量、减轻负性情绪。这是由于党参中的多糖、皂苷可调节下丘脑-垂体-肾上腺轴功能,降低应激激素水平而产生镇静作用,并能增加脑内神经递质γ-氨基丁酸含量,抑制中枢神经系统兴奋性而帮助睡眠[16]。茯神所含的多糖具有镇静、调节中枢神经元兴奋性的作用[17]。白芍中的芍药苷可作用于中枢神经系统,抑制神经系统兴奋,具有镇静、抗焦虑作用,有助于改善睡眠质量[18]。柴胡所含的皂苷可调节下丘脑-垂体-肾上腺轴功能,影响单胺类神经递质释放,减轻焦虑、抑郁等不良情绪,从而改善睡眠质量[19]。
5-羟色胺是一种吲哚类衍生物,5-HT1受体活动增加诱导快速眼球运动期睡眠,5-HT2受体的活动增加产生慢波睡眠[20]。谷氨酸是一种兴奋性氨基酸,谷氨酸能神经元的激活导致觉醒增强[21]。γ-氨基丁酸是一种具有抑制性作用的氨基酸类神经递质,低表达时可导致觉醒神经元激发,产生持久性兴奋而致失眠[22]。褪黑素是一种胺类激素,其分泌受到松果体调控,可诱导睡眠规律,其低表达时可致失眠[23]。本研究发现,治疗后两组5-羟色胺、谷氨酸均较治疗前降低,辨证组较西药组更低;治疗后两组γ-氨基丁酸、褪黑素均较治疗前升高,辨证组较西药组更高。这一结果提示,附子汤合桂枝甘草龙骨牡蛎汤治疗心肾阳虚型失眠可调节神经递质水平。这是其治疗失眠的重要机制。这是由于生龙骨、生牡蛎所含的氨基酸、多糖、矿物质等成分可调节中枢神经系统兴奋性神经递质和抑制性神经递质的合成,从而改善睡眠质量[24-25]。
多导睡眠图是反映睡眠结构和睡眠质量的重要检测方法[26-27]。本研究发现,治疗后两组SOL、WASO均较治疗前降低,辨证组较西药组更低;治疗后两组TST、SE均较治疗前升高,辨证组较西药组更高。这一结果提示,附子汤合桂枝甘草龙骨牡蛎汤治疗心肾阳虚型失眠可改善睡眠结构,这也从另一个角度证实了附子汤合桂枝甘草龙骨牡蛎汤治疗心肾阳虚型失眠的疗效优越性[28-29]。
本研究还发现,辨证组总不良反应率与西药组相仿。这一结果提示,附子汤合桂枝甘草龙骨牡蛎汤治疗心肾阳虚型失眠的安全性良好,并未增加不良反应风险[30]。
综上所述,附子汤合桂枝甘草龙骨牡蛎汤治疗心肾阳虚型失眠可调节神经递质,改善睡眠结构,提高临床疗效。
  • 福建省卫生健康青年科研项目(2019174)
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2025年第43卷第11期
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doi: 10.13193/j.issn.1673-7717.2025.11.040
  • 首发时间:2026-10-30
  • 出版时间:2025-11-10
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福建省卫生健康青年科研项目(2019174)
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    三明市第一医院,福建 三明 365000
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2种不同金属材料的力学参数
科
Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)
属
Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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