【作者】 王育徽；

【导师】 林培政；

【作者基本信息】 广州中医药大学 ， 中医临床基础学， 2010， 博士

【摘要】 高脂血症是指由于脂肪代谢或转运异常使血浆中一种或几种脂质高于正常,可表现为高胆固醇血症,高甘油三酯血症,或两者兼有(混合型高脂血症)。近年来,随着人们生活水平的提高,社会老龄化程度的加重,疾病模式也发生了改变,传染病逐渐减少而心脑血管疾病逐年增加,成为当前影响人类健康,危害人类生命最重,发病率最高,死亡率和致残率最高的三大疾病之一。大量研究资料表明,高脂血症是脑卒中、心脏猝死、心肌梗死、冠心病等重要而独立的危险因素,而使用调脂药物纠正血脂异常,已被证实可以改善内皮功能障碍、减慢粥样硬化斑块的进展、降低心肌缺血和急性冠状动脉综合征的发病率及致死率,是心脑血管疾病一级预防和二级预防的有力措施。所以医学界非常重视对高血脂的研究,如何有效的调节血脂水平,对于防治心脑血管疾病有重要的意义。肝脏是血脂代谢的重要场所,调脂药物也主要在肝脏作用,调脂药物的肝脏毒性是妨碍其临床应用的原因之一。中医药对高脂血症的认识有其独特的理论,大量小样本临床研究证实具有较好的疗效。自拟降脂散为纯中药制剂,本研究应用此药物观察其对于血脂异常的作用,希望为临床医生提供一种安全有效的调脂药物。目的观察自拟降脂散治疗高脂血症的临床疗效和安全性,以期为临床应用提供安全性和药效学依据。方法1.病例纳入标准(同时符合以下四条,方可纳入观察病例)(1)符合中医辨证及西医诊断标准。符合上述高脂血症诊断的高脂血症病人。(2)年龄在18-70岁之间。(3)虽服用调脂药物,但已停药两周以上,血脂水平仍符合诊断标准。(4)患者志愿受试并签署知情同意书。2.病例排除标准(符合以下任何1条,不得纳入观察病例)(1)不符合中医辨证及西医诊断标准。不符合上述诊断标准和纳入标准者。(2)半年内患有心肌梗塞、脑血管意外、严重创伤或做过重大手术者。(3)肾病综合症、甲状腺功能减退、急性和慢性肝胆疾病、糖尿病及痛风病人。(4)由药物引起的高脂血症。(5)正在使用肝素、甲状腺治疗药和其他影响血脂代谢药的病人以及近4周内(6)采用其他降血脂措施的病人。(7)孕妇及哺乳期妇女。(8)合并有其他严重器质性病变,医生认为不适合者。(9)过敏体质及精神病病人。3.病例分组全部病例均来源于台湾东肠中医诊所就诊病人60例。西医诊断为高脂血症,中医分型为痰浊阻遏证、脾肾阳虚证、肝肾阴虚证、气滞血瘀证、阴虚阳亢证。采用随机对照试验方法,将合格受试者以1：1的比例分配至治疗组和对照组,每组30例,整个实验过程中无病例脱落。两组病例在人口学资料、一般生命体征、病情资料等方面比较,经统计学分析处理无显著性差异,P>0.05,具有可比性。4.治疗方法(1)治疗组：自拟降脂散,研末装胶囊口服,每次9g,每日3次,疗程60天。(2)对照组：胆固醇清片(制造商：加拿大Omega Inc,规格：240粒／瓶,450mg／粒,准字号：300091)5.观察指标(1)安全性观测①一般体格检查项目(含体重、血压、心率)。②血、尿、粪常规化验。③心电图检查,肝、肾功能检查。以上项目治疗前3天内,疗程结束±3天内各检测1次,共两次。(2)疗效性观测(对观察做相关统计学分析处理)①相关症状与体征：治疗前3天内观察记录1次,治疗过程中每两周察记录1次,直至治疗结束。②体重：治疗前3天内观察记录1次,治疗过程中每周观察记录1次,直至治疗结束。③血脂检测：检测(计算)TC、TG、HDL-c、LDL-c等,治疗前、后3天内各一次。④载脂蛋白apoAI、apoB100测定,治疗前、治疗后3天内各一次。⑤血液流变学测定：检测全血比粘度(高切、低切)、血浆比粘度、血沉、红细胞压积,治疗前、治疗后3天内各一次。结果1.对两组治疗前后临床综合症状总疗效比较,差异有统计学意义(秩和检验,P<0.01),其中两组总有效率的比较经卡方检验差异亦有统计学意义,可认为治疗组疗效高于对照组。2.对两组中医单项症状疗效比较,头晕症状、腹胀纳呆症状、头痛症状、肢麻沉重症状、心悸症状、失眠症状、胸闷痛症状、二便异常症状两组改善程度,差异有统计学意义(秩和检验,P<0.05),可认为治疗组中医单项症状的改善优于对照组。3.对两组治疗后中医单项症状消失率比较,在头晕、头痛、肢麻沉重、失眠、胸闷痛、二便异常症状消失率比较上,差异有统计学意义(卡方检验,P<0.05),可认为治疗组单项症状的消失率高于对照组。4.对两组治疗前后舌象、脉象变化比较,舌淡胖、苔滑腻、脉弦滑消失率比较,差异有统计学意义(卡方检验,P<0.05),可认为治疗组消失率高于对照组。5.对治疗前后血脂指标(TC、TG、HDL-C、LDL-C、Lp(a))变化,两组组内比较,差异有统计学意义(配对t检验,P<0.05),提示经治疗后两组病例的高血脂状态得到明显改善；两组组间比较,两组治疗后TC、HDL-C的比较,差异有统计学意义(成组t检验,P<0.05)。6.对治疗前后载脂蛋白(apoAI、apoB100)变化,两组组内比较,差异有统计学意义(配对t检验,P<0.05),提示经治疗后两组病例的该类指标改善明显；两组治疗后组间比较,提示组间比较差异无统计学意义(成组t检验,P>0.05)。7.对治疗前后血流变指标(全血粘度高切、全血粘度低切、血浆比粘度、)变化,两组组内比较,差异有统计学意义(配对t检验,P<0.05),提示经治疗后两组病例的该类指标均改善明显；两组治疗后组间比较,两组治疗后全血粘度低切、血浆比粘度、血沉、红细胞压积、纤维蛋白原比较,差异有统计学意义(成组t检验,P<0.05)。结论本次临床研究表明,自拟降脂散能有效地降低各项相关实验室指,改善证候症状,治疗高脂血症。在服药过程当中,对肝、肾功能、血常规关安全性指标没有明显影响,是一种安全有效的用药途径,发挥了中医药势,为临床的推广使用提供了有利的理论依据。更多还原

【Abstract】 ObjectiveHyperlipidemia is due to abnormal fat metabolism or abnormal transport which causing one or more kind of lipid in plasma became higher than normal, can be reflected as hypercholesterolemia、hypertriglyceridemia, or both (mixed high lipemia). In recent years, with the development of people’s living standards、the aging of societ have became worse and worse and the changed mode of the disease, contagious disease has tapered while cerebrovascular diseases has increased year by year, which become one of the three diseases of hightest effection on affecting human health, harming to human life, attacking rate, death rate and mutilation rate. A lot of research data was showed that hyperlipidemia was one of the independent risk factor of sudden cardiac death, myocardial infarction, coronary heart disease and so on, using lipid lowering drugs to correct dyslipidemia was a good powerful measure to the first-level prevention and the second-level prevention of cerebrovascular diseases by improving endothelial dysfunction, slowing porridge the progress of atherosclerotic plaque and reducing myocardial ischemia and acute coronary syndrome and mortality rates. Medical science community paid more attention on the research of the hyperlipemia which has important significance of preventing cardiovascular disease. The liver is an important site for blood-fat metabolism and adjusting cholesterol. The hepatotoxicity was a main reason for obstruct its clinical application. Traditional Chinese Medicine has its unique understanding on hyperlipoidemia which has been confirmed has the better curative effect on a large number of small sample size clinical research. The study that used Ziningjiangzhi powder (ZNP) was to observe the abnormal effect of blood-fat hoping to provide a safe and effective lipid lowering drugs for clinic. Literature review:Studied the Chinese medicine on the pathogenesis of hyperlipidemia and the information of determination of treatment based in pathogenesis obtained through differentiation of symptom and sign, we had a more comprehensive understanding of high blood lipids and overview of the development of recent drug using in disease, and summed up summary and statement. From the western medicine, provided comprehensive overview on the concept of hyperlipidemia、classification and diagnosis, also summed up the progress of drug therapy of lowering fat and got the review evaluation from clinical trials in recent years.MethodsTo observe the efficacy and safety of Ziningjiangzhi powder for treated Hyperlipidemia in order to provide the pharmacodynamic and safety basis for clinical application. Methods1. Cases internalized criteria (also subject to the following four titles)(1) Meeting the diagnostic criteria of TCM and western medicine and consisting with the diagnosis of hyperlipidemia hyperlipidemia.(2) During 18 to70 years old.(3) Although taken lipid lowering drugs, stopped using more than two weeks, the level of blood fat still met the diagnostic criteria.(4) Subjects were volunteers and signed informed consent.2. Cases exclusion criteria (in accordance with any of the following one)(1) Not meet the diagnostic criteria of TCM and western medicine, and do not meet these diagnostic criteria and inclusion standards.(2)Suffered from myocardial infarction、cerebrovascular accidents、major trauma or major surgery during six months.(3) Nephrotic syndrome, thyroid dysfunction, acute and chronic liver and gallbladder disease, diabetes and gout patients.(4)Hyperlipemia induced by drugs.(5)Patients were used heparin and other drug that treating thyroid or effecting blood-fat metabolism for nearly 4 weeks(6) Patients were used other lipid-lowering measures.(7) Pregnant and lactating women.(8)The people that were associated with other serious organic disease and doctors diagnosed as incompetence(9) Patients who had allergies and mental disease. 3. Case divided60 patients were all collected in Taiwan Dongyang clinic in TCM and diagnosed as hyperlipidemia in western medicine with typed of repression for the sputum、asdthenic splenonephro-yang、hepatic and renal yin deficiency、qi-stagnancy and blood stasis、asthenic yin causing predominant yang in TCM. The qualified patients were randomly divided at 1:1 ratio into 2 groups:the treatment group and the control group, each group was 30 cases and no cases of absence. Two groups of patients in demographics、general life signs、the condition data and so on have no significant difference(P> 0.05).4. Treatment methods:(1) The treatment group:given ZNP in caps orally,9g for each time,3 times a day,60days as a course of treatment.(2) The control group:given cholesterol clearing pellet (Manufacturer:Canada Omega Inc, Specification:240/bottle,450mg/tablets, quasi-number:300091)5. Observation of index1. Safety tested:(1) General physical examination items (including weight, blood pressure, heart rate).(2) Blood, urine, stool routine tests.(3) Electrocardiogram test, liver and kidney function tests. Before treatment, above 3 days, at the end of treatment±3 days, once at each test, two times in total.2. Observation of effect (do statistical analysis related observation)(1) Symptoms and signs:to observe and record one time in 3 days before treatment, and record symptoms and signs one time in every two weeks during the treatment, till the end.(2) Weight:to observe and record one time in 3 days before treatment, and record one time in every two weeks during the treatment, till the end.(3) Blood-fat test:detection (calculated) TC, TG, HDL-c, LDL-c, etc., one time respectively in before and end of 3 days of the treatment time.(4) To measure the apolipoprotein apoAI, apoB100 one time in before and end of 3 days of the treatment time respectively.(5) Hemorrheology:detection of whole blood viscosity (high shear, low shear), plasma viscosity, erythrocyte sedimentation rate and hematocrit one time respectively in before and end of 3 days of the treatment time. Results1. There was significant differences between two groups of before and after treatment by the using rank sum test (P<0.01), and the total curative effect effective comparison of two groups by chi-square test was statistically significant. It was considered that the curative effect in the treatment group was higher than that of in the control group.2. Using rank sum test to compare the treatment group with the control group in efficacy of individual symptoms of Traditional Chinese Medicine, there was statistically significance between than two groups in dizziness, abdominal distension and anorexia symptoms, headache, heavy limbs numbness symptoms, palpitation, insomnia, chest pain symptoms, urine and stool abnormal symptoms (P<0.05). It was considered the treatment group of efficacy of individual symptoms of Traditional Chinese Medicine improved individual symptoms better than that of the control group.3. Using chi square test to compare one group with the other group in the disappearance rate of efficacy of individual symptoms of Traditional Chinese Medicine after treatment, shows that in dizziness, headache, heavy limbs numbness, insomnia, chest pain, abnormal symptoms in the urine and stool, we compare the rate of%, the difference was statistically significance (P<0.05), can be considered individual symptoms in the treatment group rate was higher.4. There was statistical significance compared before treatment with after treatment in tongue demonstration and pulse tracings,in which tongue pale, creamy fur, slippery pulse rate% loss of comparison by using chi square test to two group(P<0.05). It was considered the disappearance rate of the treatment group was higher.5. There was statistical significance compared with the lipid parameters (TC, TG, HDL-C, LDL-C, Lp (a)) changes before and after treatment in both group by using paired t-test(P<0.05). It was showed that two cases of high blood lipid status had significantly improved. There was statistical significance between the two groups by t-test on the difference of TC> HDL-C. (P<0.05)6. There was statistical significance between two groups using paired t test on the change of apolipoprotein (apoAI, apoB100) before and after treatment (P<0.05). It was showed that the two groups were remarkable improvements after treatment. The difference between groups had not statistical significance compared with two groups after treatment by using group t-test. (P>0.05). 7. There was significant difference between two groups of changes before and after treatment on the Hemorheological indexes (whole blood viscosity, high shear, low shear whole blood viscosity, plasma viscosity) by using paired t-test (P<0.05). It was showed that the two groups of such case indicators were improving significantly after treatment. The difference of plasma viscosity, erythrocyte sedimentation rate, hematocrit product, fibrinogen had statistical significance compared within groups after treatment by using paired t-test. (P<0.05)ConclusionThe clinical study had shown that Jiang ZNP could effectively reduce the bulk lipid of the relevant laboratory index and could improve the syndrome symptoms and treatment of hyperlipidemia. In the process of taken medication, there was not significantly difference on the liver-kidney function, blood routine test, It was a safe and effective treatment medicine promoting the advantage of TCM and provided the theoretical basis for the further clinical application.更多还原