【作者】 司徒宝珍；

【导师】 罗陆一；

【作者基本信息】 广州中医药大学 ， 中医内科学， 2010， 博士

【摘要】 冠心病(冠状动脉粥样硬化性心脏病)多发生于中老年人,随着人民生活条件改善与膳食习惯的改变,冠心病的发病率已趋向年轻化。目前,它与脑卒中同为我国致残和死亡率最高的疾病,严重地威胁人们生命和健康。大量研究证实,颈动脉粥样硬化与冠状动脉粥样硬化有着相同的病理基础,两者关系密切,颈动脉粥样硬化性病变是全身动脉粥样硬化性疾病的窗口,因为颈动脉粥样硬化的发生要较冠状动脉粥样硬化为早。早期的冠心病,可以没有任何症状,临床上诊断非常困难,因而患者常常得不到适当和及时治疗。随着近年超声检查仪器和方法的完善,利用无创的颈动脉超声检查预测冠心病,达到早期有效地发现和治疗动脉粥样硬化的目的,对防治冠心病与一系列心脑血管疾病非常重要。中医药治疗冠心病与颈动脉粥样硬化有一定的特色和优势,而补肾活血化痰法更已广泛应用在冠心病心绞痛的治疗和预防之中。本研究拟探讨以“补肾活血化痰汤”治疗冠心病心绞痛患者的同时,观察研究补肾活血化痰法对患者颈动脉粥样硬化斑块的影响,以及其它相关心脑血管病症(如头痛、眩晕、视力下降、记忆力衰退等等)的治疗效果。“补肾活血化痰汤”是我校附属深圳市中医院心血管内科疾病专家、广东省名中医,导师罗陆一教授集四十多年临床经验,既充份考虑到动脉粥样硬化的病理特性,又顾虑其危险因素,并结合中老年人体质多虚的特点,以肾虚为本,瘀血、痰阻为标的机理立论,经多年验证创制而成的纯中药汤剂。是方由熟地黄、补骨脂、制首乌、怀牛膝、制半夏、制南星、石菖蒲、川芎、三七等中药组成。目的：研究中药汤剂“补肾活血化痰汤”对冠心病心绞痛的疗效及对患者颈动脉粥样硬化斑块的影响,从而进一步证实“补肾活血化痰汤”的临床疗效,为中医治疗冠心病心绞痛及颈动脉硬化斑块患者提供有疗效的新方法、新制剂。方法：选取冠心病心绞痛患者共192例,并且符合诊断、纳入标准的患者(颈动脉内中膜厚度IMT≧1mm或是颈动脉粥样硬化斑块患者),采用随机数字表法,按住院号顺序随机分为中药“补肾活血化痰汤”治疗组T、“阿托伐他汀钙”西药对照组A、和基础治疗基础组B。三组均给予基础治疗用药：口服“阿司匹林”每日1片(每片100mg),晚上服用。治疗组T采用补肾活血化痰汤治疗,每日1剂,分早晚两次温服。对照组A给予口服“阿托伐他汀钙”每日1片(每片lOmg),晚上服用。基础组B只给予基础治疗用药。各组均以90天为1个疗程。连续观察2个疗程。比较各组治疗前后颈动脉粥样硬化斑块数量、类型、内中膜厚度IMT、斑块面积、斑块Crouse积分,观察各组治疗前后临床症状、心绞痛症状、心电图、肝肾功能、电解质、血、尿和大便等三大常规指标,血脂总胆固醇TC、甘油三脂TG、高密度脂蛋白胆固醇HDL-C、低密度脂蛋白胆固醇LDL-C、C反应蛋白CRP、与血流变的指标。再作统计学分析,得出结果,完成临床研究。结果：治疗组T补肾活血化痰汤治疗后,在颈动脉粥样硬化疗效上,显效率46.03%,总有效率为83.87%,与对照组A比较则无显著性差异(P>0.05),而与基础组B比较,则有非常显著差异(P<0.01)；各类型斑块数目均明显下降,斑块总数由128个降到89个,有非常显著差异(P<0.01),与对照组A比较则无显著性差异(P>0.05),而与基础组B比较,则有非常显著差异(P<0.01)；治疗组T治疗后内中膜厚度(IMT)、斑块面积、Crouse积分均明显下降,有非常显著差异(P<0.01),但与对照组A、基础组B比较(除基础组B, Crouse积分外)则无显著性差异(P>0.05),治疗组T在Crouse积分比较基础组B,则有非常显著差异(P<0.01)；在心绞痛疗效上,治疗组T痊愈率42.86%,显效率50.79%,总有效率为87.30%；心电图改善显效率52.38%,总有效率为87.30%。心绞痛程度改善、心绞痛临床症状积分改善、心电图疗效、及心绞痛总体疗效均明显优于阿托伐他汀钙对照组A及基础治疗基础组B,有非常显著差异(均P<0.01)；在中医临床症状总体疗效上,治疗组T显效率47.62%,总有效率为85.71%。治疗组T治疗后,各项中医临床症状除记忆力衰退一项外,P=0.000<0.01,有非常显著性差异。中医临床症状总体积分改善、个别症状积分改善(除记忆力衰退、视力下降外)、及中医临床症状总体疗效均明显优于对照组A及基础组B,有非常显著差异(P<0.01)或显著差异(P<0.05)；在调控血脂方面,治疗组T患者治疗后甘油三脂TG、总胆固醇TC、低密度脂蛋白胆固醇LDL-C均得到明显降低,高密度脂蛋白胆固醇HDL-C明显升高,有非常显著差异(均P<0.01),但与对照组A比较则无显著性差异(均P>0.05),而与基础组B比较TG、HDL-C有非常显著差异(均P<0.01),TC、LDL-C则无显著差异(均P>0.05)；在降低炎症因子C反应蛋白值上,治疗组T患者治疗后,CRP值明显下降,有非常显著差异(P<0.01),与对照组A比较则无显著性差异(P>0.05),而与基础组B比较,则有非常显著差异(P<0.01)；在血液流变学指标改善上,治疗组T治疗后,全血粘度(高切)、全血粘度(低切)、红细胞压积、血浆比粘度均明显下降,有非常显著差异(P<0.01),与对照组A、基础组B比较(除血浆比粘度外)则无显著性差异(P>0.05),但血浆比粘度比较则有非常显著性差异(P<0.01)。最后,经直线相关分析,结果显示心绞痛症状积分值和相应的颈动脉内中膜厚度IMT的相关系数为0.819,P=0.000,有统计学意义。可以认为心绞痛症状积分值与颈动脉内中膜厚度呈正相关性。结论：补肾活血化痰汤治疗冠心病心绞痛疗效显著,未发现毒性副作用,安全可靠。除治疗心绞痛外,患者颈动脉粥样硬化症状亦显著得到改善。补肾活血化痰汤且具有调脂、降低炎症因子,改善血液流变学指标作用,能减少或抑制颈动脉粥样硬化斑块的形成,并可改善心脑血管疾病的整体临床症状,从而达到抑制颈动脉、以致整体动脉粥样硬化,顾护心脑血管,防范治疗心肌缺血,脑缺血,预防心脑血管事故的发生。最后,本研究显示心绞痛症状积分值和相应的颈动脉内中膜厚度呈正相关性,可以认为心绞痛与颈动脉粥样硬化关系密切。更多还原

【Abstract】 Coronary Atherosclerotic Heart Disease CAD is mostly happen to middle-aged or older people, with improvement in people’s living condition and c hange of their diet habit, there is a trend of increasingly younger peopl e having CAD. Today CAD and Stroke are two main diseases that lead to hig hest rate of disability and death in China, and continue be a major threa t to peoples’health and lives. A large number of research have concluded that Carotid Arterioles Atherosclerosis CAS and CAD have same dangerous f actors and common mechanism, there are close relationships between the tw o. CAS happens earlier than other Arthroscleroses AS, and thus can be use d as a window to detect CAD. Early stages CAD are normally with no sympto m and very difficult to detect, therefore most patient missed proper and timely treatment. Nowadays with the advancement in ultrasonic technology and method, the ultrasonic scanning of CAS become an effective method of detecting CAD in its early stage, and this is very important to prevent a nd decrease incidences of CAD and most Cardiovascular and Cerebrovascular Diseases CCVD. Traditional Chinese Medicine has its superiority and dist inction in treatment of CAD and CAS diseases, and Bushenhuoxuehuatan meth od has already been widely used in treatment of Angina Pectoris. This res earch is an innovative study; the value is to study the curative effects on Atherosclerotic plaque in Carotid artery when treating patients of Ang ina Pectoris of CAD by Bushenhuoxuehuatan Decoction, and at the same tim e investigate the curative effect on other CCVD symptoms as well. Bushenh uoxuehuatan Decoction is invented by my tutor, Guangdong famous TCM prac titioner, Specialist of Internal medicine Shenzhen Hospital of TCM, Profe ssor LUO Luyi, the decoction is a pure Chinese medicine composition and h as been tested and refined for over forty years of clinical practices tre ating AS diseases. Based on the concept that root cause of AS is kidney i nsufficiency, and the incidental factors are blood stasis, and phlegm-hu mor stagnation, Professor LUO tailored the decoction which mainly compose d of Rehmannia glutinosa, Psoralea corylifolia, Polygonum multiflorum, Ac hyranthes bidentata Blume, Pinellia ternate, Arisaema consanguineum Schot t., Acorus gramineus Soland and Ligusticum chuanxiong Hort.Purpose:Observing the curative effects on Atherosclerotic plaque in Carotid artery when treating Angina Pectoris patients with Bushenhuoxuehuatan Decoction, thus to provide additional research justification for the effectiveness and refinement of the decoction.Methods:192 valid patients were divided into treatment group T, control group A and foundation group B by the simple randomization. All cases for all thr ee groups were given the same foundation treatment:Apsin (one 100mg tabl et at night per day).The treatment group T was treated with Bushenhuoxueh uatan Decoction (one dose per day separately half portion warmly taken mo rning and at night), while control group A was treated by the Atorvastati n calcium (one 10mg tablet at night per day) and foundation group B was t reated only by foundation treatment.90 days would be a course of treatme nt for all three groups, and two courses of treatment were observed. The type and quantities of CAS plaques, intima-media thickness (IMT), plaques area and Crouse scores were detected by Ultrasonic scanning. The patient s’symptoms, Angina Pectoris symptoms, electrocardiogram, hepatic functio n, renal function, electrolytes examination and the three main routine ex aminations before and after the treatment of the three groups were detect ed. And as well as hemo-axungia examination, C-reactive protein measureme nt and hemorheology examination were detected as well. Then, the data woul d be analyzed by statistical analysis to get the results and conclusion.Result:The curative effect of the Bushenhuoxuehuatan Decoction is described as follow:For CAS curative effect, predominant effect rate 46.03%, total effect rate 83.87%, there are no significant difference with Atorvastatin calcium control group A(P>0.05), but there are very significant difference with foundation treatment foundation group B(P<0.01). Treatment group T has significantly reduced the quantities of plaques for all types of CAS plaques, total quantity reduced from 128 to 89, there are very significant difference before and after treatment(P<0.01), and there are no significant difference with control group A(P>0.05), but there are very significant difference with foundation group B(P<0.01). Treatment group T has very significantly reduced the intima-media thickness (IMT), very significantly reduced plaques area and very significantly reduced Crouse scores, there are very significant difference (P<0.01). However there are no significant difference between treatment group T and control group A & foundation group B (P>0.05), except on Crouse scores that Treatment group T and foundation group B has very significant difference(P<0.01); Angina Pectoris cure rate 42.86%, predominant effect rate 50.79%, total effect rate 87.3%. Electrocardiogram predominant effect rate 52.38%, total effect rate 87.3%. For curative effect on the extend of Angina Pectoris attacks, Angina Pectoris symptoms, Electrocardiogram cure rate, and the total Angina Pectoris cure rate, Bushenhuoxuehuatan Decoction treatment group is more effective than Atorvastatin calcium control group A and foundation treatment foundation group B, there is very significant difference between treatment group T and the two other groups (P<0.01); Total TCM Symptom Integral predominant effect rate 47.62%, total effect rate 85.71%. All individual TCM Symptom are improved after treatment except memory improvement, (P<0.01), there is very significant difference. Treatment group is more effective than two other groups except memory and eyesight improvements, there are very significant and significant difference between the groups (P<0.01 or P<0.05); In hemo-axungia examination, treatment group T has significant curative effect in lowering TG, TC, LDL-C, while rising HDL-C values, there are very significant difference (P<0.01) after treatment. However there are no significant difference with control group A (P>0.05), and no significant difference with foundation group B (P>0.05)on TC, LDL-C, but has very significant difference with foundation group B (P<0.01) on TG, HDL-C; After treatment, treatment group T has significant reduced C-reactive protein (CRP) value, there are very significant difference (P<0.01). Compared to control groups, there are no significant difference with control group A (P>0.05), but has very significant difference with foundation group B (P<0.01); In hemorheology examination, treatment group has significantly reduced blood viscosity (high and low cut), plasma viscosity, and hematocrit, there are very significant difference (P<0.01). However there are no significant difference between treatment and two other groups (P>0.05) except for plasma viscosity there are very significant difference between treatment and control groups (P<0.01). Finally after straight line correlation analysis, Angina Pectoris symptom scores and IMT has shown direct positive relationship, correlation factor 0.819, P=0.000<0.01, has very significant statistical meaning.Conclusions:The Bushenhuoxuehuatan Decoction has outstanding curative effect on Angina Pectoris of Coronary Heart Disease, and at the same time all CAS symptoms of the patient were significantly improved, in the entire course of treatment no adverse drug reaction was observed. Bushenhuoxuehuatan Decoction, with its functions of adjusting the hemo-axungia, reduce C-reactive protein and improving hemorheology, could hinder and defer CAS plaque development, improve symptoms of CCVD, protect and cure CAS and AS diseases, and ultimately prevent and decrease incidences of CAD and most CCVD Diseases更多还原