黄连清降合剂治疗高血压病的临床与实验研究
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摘要
本文是在导师的指导下,通过研究高血压病自身的临床特点及环境因素、情志活动、生活方式、饮食习惯、体质变化与高血压病的关系,旨在探讨高血压病新的发病机制,以寻求治疗高血压病的有效方药。提出了高血压病心肝火旺、热毒内盛的病机假说。以泻肝宁心、清热解毒为治疗大法,精选药物,合理组方,采用科学的制备工艺及质量标准,制成黄连清降合剂,对35例高血压病Ⅰ级、Ⅱ级患者进行了临床观察,与牛黄降压丸的30例患者作对照,并结合动物实验以验证药物的疗效。
     结果表明:试验组降压显效率为62.86%,总有效率为85.71%;症状改善显效率为65.71%,总有效率为91.42%。对照组降压显效率为23.33%,总有效率为70%;症状改善显效率为20%,总有效率为73.33%。经统计学处理,两组有显著性差异(P<0.05)。此外还观察了黄连清降合剂对试验组29例患者24h动态血压的变化。结果表明:本药有良好的改善患者24h动态血压的平均变化,降低患者白昼收缩压及舒张压负荷,夜间收缩压及舒张压负荷,改善谷峰比值,经治疗前后的统计学处理,有显著性差异(P<0.05)。其次尚能降低血脂,改善血液流变学,改善心肌缺血及心律失常,提高心脏的舒张功能,改善眼底的动脉硬化,且无毒、副作用。
     动物实验表明:黄连清降合剂可明显降低自发性高血压大鼠(SHR)的收缩压,呈现明显的时效、量效关系。降低SHR血浆血管紧张素Ⅱ(AngⅡ)浓度,降低SHR血浆内皮素(ET)及去甲肾上腺素(NE)的含量,降低心/体比值、肾/体比值,改善主动脉及肾动脉的“构型”改变,降低肾动脉中膜厚度/管腔半径、中膜面积/管腔面积的比值,在某种程度上具有逆转SHR靶器官损害的作用。
     研究结论:心肝火旺、热毒内盛是导致高血压病的重要病机:泻肝宁心、清热解毒是高血压病的重要治法。黄连清降合剂不仅具有显著的临床疗效,而且具有可靠的实验药效学指标,是治疗高血压病的有效复方。其治疗高血压病的机制可能与RAS、ET、NE有关。本项研究提出了热毒内盛是导致高血压病的病机理论,丰富了中医药对高血压病的治疗学内容,为高血压病的中医药治疗开辟了一条新的途径。
Based on the studies of the hypertension's clinical features and the relationships between this disease and the environmental factors, the emotional activities, the life styles, the diet habits, the physique, this thesis explores the new etiology pathogenesis of the hypertension in order to find a new effective prescription to treat it. The research puts forward the pathogenetic hypothesis, which is the hypertension ascribes in the intense fire in the heart and the liver, excess of evil heat in the interior. The principle of therapy is purging
    the liver and tranquilizing the heart, clearing the heat and detoxify. According to this, herbs are choosed precisely and the prescription is composed rationally, then the HLQJ (Huanglian Qingjiang) mixture is prepared by using modern technology. 35 patients with hypertension I or II were treated by taking HLQJ mixture, with another 30 hypertension patients taking Niuhuang Jiangya pills as the control group. The result of animal experiment is also a proof of its effect.
    As for the HLQJ mixture group, the prominent effective rate in blood pressure reducing is 62.86% and the total effective rate is 85.71%. The effective rate of improving symptoms is 65.71% and the total effective rate is 91.42%. As for the control group: the prominent effective rate in blood pressure reducing is 23.33% and the total effective rate is 70%. The effective rate of improving symptoms is 20% and the total effective rate is 73.33%. There is significant difference between the two groups (P<0.05). In addition, the effect of the HLQJ mixture on the patients' 24-hour dynamic blood pressure was observed. Results show that the HLQJ mixture can improve the
    
    
    averaged change of the 24-hour dynamic blood pressure of the patients. Furthermore, the systolic and diastolic pressure in daytime and night were both lowered. And the ratio between the highest and the lowest can be improved. There is significant difference before and after the therapy (P<0.05). The HLQJ mixture can also lower the lipoprotein in the blood, improve the hemorheology, the myocardial ischemia and the cardiac arrhythmia, enhance the diastolic function of the heart and improve the arteriosclerosis in eyegrounds. And it has no toxicity and side effects.
    The animal experiments show that the HLQJ mixture can obviously lower the systolic pressure of SHR, appearing evident time-effect and dosage-effect. It can lower the content of Angll, ET-1 and NE in SHR's plasma, decrease the ratios between the heart and the body, the kidney and the body, improve the change in the structure of the aorta and kidney artery, and reduce the ratios between the thickness of the artery mesosphere and semi diameter of the vessel, the surface area of mesosphere and the surface area of the vessel. In some degree, it has the ability to deteriorate the damage in the target organ of SHR.
    Intense fire in the heart and the liver and excess of evil heat in the interior are the important mechanism of the hypertension. So purging the liver and tranquilizing the heart, reducing the fire and detoxifying are the important therapies to the hypertension. The HLQJ mixture has not only prominent clinical curative effect, but also substantial pharmacologic and potent fundament. It is an effective compound prescription of treating hypertension. The mechanism of the HLQJ mixture treating hypertension maybe has relationship with RAS, ET and NE. This paper puts forward the pathogenetic theory that the hypertension
    ascribes to evil heat production in the interior. It enriches the therapeutics of TCM treating hypertension and provides a new way for the therapy to the hypertension with TCM.
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