摘要
目的观察温肾益心方加减辅助治疗冠心病合并甲状腺功能减退症(甲减)脾肾阳虚证的临床疗效及可能的作用机制。方法135例冠心病合并甲减脾肾阳虚证患者依照患者服用中药的意愿分为对照组67例和治疗组68例。对照组予以常规西药治疗,治疗组在对照组基础上加用温肾益心方加减口服,每日1剂,两组均治疗8周。比较两组患者治疗前后中医证候积分、心绞痛积分、简明生活质量量表(SF-36)评分、甲状腺功能指标[包括促甲状腺激素(TSH)、甲状腺素(T4)、三碘甲状腺原氨酸(T3)]及血清环磷酸腺苷(cAMP)、环磷酸鸟苷(cGMP)、单核细胞趋化因子配体2(CCL2)、肿瘤坏死因子相关激活蛋白(CD40L)水平,比较两组患者治疗后甲状腺激素制剂用药量及减停率,评价中医证候疗效及心绞痛疗效,并进行安全性评价。结果通过倾向性评分匹配法调整偏倚,最终纳入统计分析102例,两组各51例。治疗组与对照组中医证候疗效总有效率[94.12%(48/51)与64.71%(33/51)]、心绞痛疗效总有效率[80.39%(41/51)与62.75%(32/51)]、甲状腺激素制剂减停率[39.21%(20/51)与5.88%(3/51)]比较,治疗组均高于对照组(P<0.05或P<0.01)。与本组治疗前比较,两组治疗后中医证候总积分、各项主症单项评分、主症积分、次症积分以及心绞痛积分、TSH水平均降低(P<0.01),SF-36各维度评分、T4、T3、cAMP水平均升高(P<0.05或P<0.01);治疗组治疗后甲状腺激素制剂用药量及血清cGMP、CCL2、CD40L水平较治疗前降低(P<0.01)。治疗后治疗组中医证候总积分,主症积分,主症中胸闷、胸痛、畏寒、四肢不温、腰膝酸软单项评分,次症积分以及心绞痛积分,以及TSH、cGMP、CCL2、CD40L水平均低于对照组(P<0.05或P<0.01),而SF-36各维度评分、T4、T3、cAMP水平均高于对照组(P<0.01)。治疗期间共发生不良事件3例,经判断均与本研究治疗用药无关。结论温肾益心方加减辅助治疗冠心病合并甲减脾肾阳虚证可显著改善患者中医证候、心绞痛症状、生活质量及甲状腺功能,并可促进甲状腺激素制剂的减停,其机制可能与调节cAMP/cGMP平衡及下丘脑-垂体-甲状腺(HPT)轴,从而降低免疫炎症水平有关。
Objective To observe the clinical efficacy and relative mechanism of the Modified Wenshen Yixin Formula(温肾益心方加减,MWYF)as an auxiliary treatment of coronary heart disease(CHD)complicated with hypo⁃thyroidism of spleen-kidney yang deficiency.Methods A total of 135 CHD patients complicated with hypothyroidism and spleen-kidney yang deficiency were included and divided into control group(67 cases)and experimental group(68 cases)according to the patients'wishes of herbal medicine administration.The control group was given conven⁃tional western medicine,while the treatment group was additionally given MWYF,1 dose per day;both groups were treated for 8 weeks.The traditional Chinese medicine(TCM)syndrome scores,angina scores,SF-36 scores,thyroid function indicators including thyroid stimulating hormone(TSH),thyroxine(T4)and triiodothyronine(T3),as well as serum cyclic adenosine monophosphate(cAMP),cyclic guanosine monophosphate(cGMP),monocyte chemoat⁃tractant ligand 2(CCL2),and tumor necrosis factor-related activator protein(CD40L)levels before and after treat⁃ment were compared between the two groups.The dosage and reduction and discontinuation rate of thyroid hormone preparations after treatment were compared between the two groups.The effectiveness regarding TCM syndrome and angina pectoris was evaluated,and the safety was assessed.Results Bias was adjusted by matching on propensity score,and 102 cases were finally included in the statistical analysis,with 51 cases in each group.The total effective rate regarding TCM syndrome[94.12%(48/51)versus 64.71%(33/51)],the total effective rate regarding angina pectoris[80.39%(41/51)versus 62.75%(32/51)],and the reduction and discontinuation rate of thyroid hormone preparation[39.21%(20/51)versus 5.88%(3/51)]were significantly higher in the experimental group than those in the control group(P<0.05 or P<0.01).After treatment,the total TCM syndrome score,individual scores of major symptoms,the major symptoms score,the secondary symptoms score,angina pectoris score,and TSH level were significantly reduced(P<0.01),while all dimensions of SF-36 scores,T4,T3,and cAMP levels significantly increased in both groups(P<0.05 or P<0.01).The dosage of thyroid hormone preparations and the levels of cGMP,CCL2,and CD40L in the experimental group significantly decreased after treatment(P<0.01).When com⁃pared between the two groups after treatment,the total TCM syndrome score,the major symptoms score,the scores of individual major symptom(chest tightness,chest pain,fear of cold,cold limbs,waist and kness soreness and weakness),the secondary symptoms score,angina pectoris score,TSH,cGMP,CCL2,and CD40L levels of the experimental group were significantly lower than those of the control group(P<0.05 or P<0.01),while all dimension scores of SF-36,T4,T3,and cAMP levels were significantly higher(P<0.01).A total of three adverse events occurred during treatment,none of which were judged to be related to the interventions of this study.Conclusion MWYF can significantly ameliorate the TCM syndrome,angina pectoris,quality of life and thyroid function in CHD patients complicated with hypothyroidism and spleen-kidney yang deficiency,and can promote the reduction and discontinuation of thyroid hormone preparations.The mechanism may be related to the regulation of cAMP/cGMP balance,the regulation of hypothalamic-pituitary-thyroid metabolic axis and the reduction of immune inflammation.
作者
李澳琳
严志鹏
廉璐
张倩倩
张弛
朱波宇
魏蕾
杨智涵
张军平
LI Aolin;YAN Zhipeng;LIAN Lu;ZHANG Qianqian;ZHANG Chi;ZHU Boyu;WEI Lei;YANG Zhihan;ZHANG Junping(First Teaching Hospital of Tianjin University of Traditional Chinese Medicine/National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion,Tianjin,300381;Graduate School of Tianjin University of Traditional Chinese Medicine)
出处
《中医杂志》
CSCD
北大核心
2024年第20期2116-2125,共10页
Journal of Traditional Chinese Medicine
基金
国家自然科学基金(81774232)
国家中医药管理局2021年岐黄学者支持项目(国中医药人教函〔2022〕6号)
天津市卫生健康委员会天津市名中医(津卫中〔2020〕732号)。
关键词
冠心病
甲状腺功能减退症
脾肾阳虚
温肾益心方
下丘脑-垂体-甲状腺轴
免疫炎症
coronary heart disease
hypothyroidism
Wenshen Yixin Formula(温肾益心方)
spleen-kidney yang deficiency
hypothalamic-pituitary-thyroid axis
immunoinflammation
