脉通君安汤治疗气虚血瘀型冠心病心绞痛的临床疗效及转录组学研究

Clinical Efficacy and Transcriptomic Study on the Treatment of Coronary Heart Disease Angina of Qi Deficiency and Blood Stasis Type with Maitong Jun'an Decoction

  • 摘要:
      目的  观察脉通君安汤治疗气虚血瘀型冠心病心绞痛的临床疗效, 并通过转录组学方法初步阐明其可能的作用机制。
      方法  将符合纳入标准的140例气虚血瘀型冠心病心绞痛患者依据随机数字法分为治疗组、对照组各70例, 治疗期间对照组脱落3例。对照组予冠心病二级预防西医基础治疗, 治疗组在对照组治疗基础上加服脉通君安汤, 2组疗程均为8周。治疗前后评估2组患者中医证候积分、加拿大心血管学会(Canadian cardiovascular society, CCS)心绞痛分级、西雅图量表(Seattle angina questionnaire, SAQ)评分、焦虑自评量表(Self-rating anxiety scale, SAS)评分、抑郁自评量表(Self-rating depression scale, SDS)评分及不良反应, 并基于性别、年龄、病程相匹配原则选取9例患者治疗前后外周血进行转录组学测序。
      结果  治疗后, 2组患者中医证候积分均明显下降(P < 0.01), 治疗组在改善胸痛、胸闷、气短、神倦乏力及总分方面优于对照组(P < 0.05,P < 0.01);治疗组CCS心绞痛分级总改善率优于对照组(P < 0.05);2组治疗前后SAQ、SAS及SDS评分均显著改善(P < 0.01), 治疗组SAQ评分改善优于对照组(P < 0.05, P < 0.01)。转录组学结果显示, 治疗前后具有显著差异表达的mRNA有862个, 包括509个上调, 353个下调;GO分析结果显示差异表达的mRNA生物学过程有666条, 主要包括病毒基因表达、翻译启动、RNA分解代谢过程等,细胞组分112条, 主要包括黏着斑、核糖体亚基、核斑点等;分子功能有94条, 主要包括双链RNA结合、钙黏蛋白结合、转录共调节因子活性等;KEGG分析结果显示差异mRNA富集信号通路包括20条, 主要包括甘油磷脂代谢通路、单磷酸腺苷激活的蛋白激酶(AMP-activated protein kinase,AMPK)信号通路、核糖体通路等。
      结论  脉通君安汤能够改善气虚血瘀型冠心病心绞痛患者临床症状,其作用机制为多靶点多通路,可能与甘油磷脂代谢通路、AMPK信号通路、核糖体通路的调节相关。

     

    Abstract:
      OBJECTIVE  To observe the clinical efficacy of Maitong Jun'an Decoction in treating coronary heart disease (CHD) angina of qi deficiency and blood stasis type, and preliminarily elucidate its possible mechanism of action through transcriptomics methods.
      METHODS  A total of 140 patients with CHD angina of qi deficiency and blood stasis type were included and randomly divided into a treatment group and a control group, with 70 cases in each group. During the treatment period, 3 patients in the control group dropped out. The control group received basic Western medicine treatment for secondary prevention of CHD, while the treatment group received Maitong Jun'an Decoction in addition to the treatment in the control group. The treatment period for both groups was 8 weeks. Before and after treatment, the patients in both groups were evaluated for the TCM syndrome score, Canadian Cardiovascular Society (CCS) angina grading, Seattle angina questionnaire (SAQ) score, self-rating anxiety scale (SAS), self-rating depression scale (SDS) score, and adverse reactions. The peripheral blood of 9 patients before and after treatment was selected for transcriptomic sequencing based on the principle of gender, age, and disease duration matching.
      RESULTS  After treatment, the TCM syndrome scores and total scores of the 2 groups were significantly reduced(P < 0.01). The treatment group was better than the control group in improving chest pain, chest tightness, shortness of breath, fatigue and total score (P < 0.05, P < 0.01); the overall improvement rate of CCS angina grading in the treatment group was better than that in the control group (P < 0.05); the SAQ, SAS and SDS scores of the 2 groups were significantly reduced before and after treatment (P < 0.01), and the SAQ score of the treatment group was improved better than that of the control group (P < 0.05, P < 0.01). The transcriptomics results showed that there were 862 significantly different mRNAs before and after treatment, including 509 up-regulated and 353 down-regulated. GO analysis showed that there were 666 biological processes in the differentially expressed mRNAs, mainly including viral gene expression, translation initiation, RNA catabolism, etc. There were 112 cell components, mainly including focal adhesion, ribosome subunit, nuclear spot, etc. There were 94 molecular functions, mainly including double-stranded RNA binding, cadherin binding, transcription co-regulatory factor activity, etc. KEGG analysis showed that the differentially expressed mRNAs enriched in 20 signaling pathways, mainly including glycerophospholipid metabolism pathway, AMPK signaling pathway, ribosome pathway, etc.
      CONCLUSION  Maitong Jun'an Decoction can improve clinical symptoms in patients with CHD angina of qi deficiency and blood stasis type. Its mechanism of action is multi-target and multi pathway, mainly related to the regulation of glycerophospholipid metabolism pathway, AMPK signaling pathway, ribosome pathway.

     

/

返回文章
返回