基于cAMP、cGMP探讨运用“六经欲解时”理论治疗慢性心衰伴失眠的临床研究

Clinical Study on the Treatment of Chronic Heart Failure with Insomnia by the Theory of “Six Channels Trying to Resolve Time” Based on cAMP and cGMP

目的:探讨基于cAMP、cGMP初步建立“六经欲解时”理论支持下慢性心衰伴失眠六经辨证论治体系。方法:将符合慢性心衰伴失眠六经辨证西医诊断标准的患者360例按美国纽约心脏病协会(NYHA)心功能(Ⅱ~Ⅳ级)随机分成对照组采用基础加艾司唑仑片治疗、欲解时治疗组采用欲解时基础加经方治疗、欲作时治疗组采用欲作时基础加经方治疗,观察治疗前后患者脑利钠肽(BNP)水平、匹兹堡睡眠质量指数(PSQI)、慢性心力衰竭生存质量量表(LHFQ)、心功能分级、左室射血分数(LVEF)的变化。并将各经病证组与40例健康人进行对照,观察患者及健康人23时、8时、13时、17时的环核苷酸(cAMP、cGMP)的变化。结果:心衰患者与健康人比较,太阴病证、少阴病证、厥阴病证cGMP升高,cAMP则变化不大;太阳病证、阳明病证、少阳病证cAMP升高,cGMP则变化不大。故慢性心衰可见太阳病证、阳明病证、少阳病证、太阴病证、少阴病证、厥阴病证。慢性心衰伴失眠患者在欲作时三阴经cGMP升高明显,三阳经cAMP升高明显,欲解时有所升高,但与正常组比较差异无显著性。可见慢性心衰患者血浆cAMP、cGMP昼夜节律与其睡眠剥夺有关。依据慢性心衰伴失眠的六经证型,予以基础治疗的同时,基于六经病欲解时治疗上选方较为多样性,但以四逆汤、麻黄细辛附子汤、乌梅丸为主要用方。与加用西药艾司唑仑片单纯镇静安眠、抗焦虑比较,采用六经病欲解时辨证论治,对于治疗前后生存质量、睡眠质量及心功能等指标的改善具有明显优势。结论:慢性心衰伴失眠患者血浆cAMP、cGMP水平与六经欲解时存在一定关系,可作为辨证参考依据。

Objective To discuss the establishment of syndrome differentiation and treatment system of chronic heart failure with insomnia on the basis of the theory of “Six Meridians for resolving time”based on cAMP and cGMP. Methods 360 patients with chronic heart failure(NYHA) and insomnia were randomly divided into three groups according to Nyha(Class II-IV). The Control Group was treated with basic plus Estazolam, the treatment group was treated with basic plus classical prescriptions, and the treatment group was treated with basic plus classical prescriptions, before and after treatment, the level of brain NPPB(BNP),Pittsburgh Sleep Quality Index(PSQI), living with heart failure questionnaire(LHFQ),cardiac function classification and left ventricular ejection fraction(LVEF) were observed. The changes of cyclic nucleotides(cAMP,cGMP) at 23,8,13 and 17 hours in patients and healthy people were observed.Results Compared with healthy people, the cAMP of Taiyin Syndrome, Shaoyin Syndrome and Jue yin Syndrome increased little, but the cAMP of Taiyin Syndrome, Yangming Syndrome and Shaoyang Syndrome increased little. Therefore, chronic heart failure can be seen Taiyang Disease Syndrome, Yangming Disease Syndrome, Shaoyang Disease Syndrome, Taiyin Disease Syndrome, Shaoyin Disease Syndrome, Jueyin Disease Syndrome. In patients with chronic heart failure and insomnia, the cGMP of Sanyin Meridian increased obviously, cAMP of Sanyang Meridian increased obviously, but there was no significant difference compared with normal group. The circadian rhythm of cAMP and cGMP in plasma was related to sleep deprivation in patients with chronic heart failure. According to the Six Meridians Syndrome of chronic heart failure with insomnia, the basic treatment was given, while the treatment based on the Six Meridians disease was more diverse, but Sini decoction, Mahuang Xixin Fuzi decoction and Wumei pill were mainly used. Compared with Estazolam alone, sedation and anti-anxiety, the treatment based on differentiation of symptoms and signs of the Six Meridians is better for the improvement of life quality, sleep quality and heart function before and after treatment. Conclusion The levels of cAMP and cGMP in plasma of patients with chronic heart failure and insomnia are related to the resolution of Six Meridians.