血脂康治疗不同中医证型高脂血症的疗效观察
|
摘要
高脂血症(Hyperlipemia,HLP)作为一种人体脂质代谢异常的亢进“模型”,临床上主要表现为血浆血脂含量高于正常水平,是一种对人体危害极大的心血管系统病症。根据目前世界各国对高脂血症的研究进展,我们已经清楚地认识到高脂血症将极大地促进动脉粥样硬化的发生与发展,由此增加与之关系密切的冠心病、脑卒中、肾动脉硬化、周围血管硬化等重大疾病的发病率,所以对于高脂血症的治疗各国都非常重视,各种药物的开发和临床研究方兴未艾。血脂康胶囊是近十年来临床上广泛应用且被证明具有肯定疗效的纯中药降脂制剂,但临床实践中发现血脂康对高脂血症患者的疗效存在差异性。因此,从中西医两种角度地对血脂康临床治疗不同中医证型高脂血症的疗效进行观察研究,充分探明其疗效的差异性,以求更加科学地指导其临床应用将至关重要,也具有深远的意义。本临床研究对300名服用血脂康的患者进行调脂治疗,对其临床疗效进行观察和分析,旨在探明血脂康对不同中医证型高脂血症的疗效差异,分析其产生的原因,为进一步指导临床合理用药奠定基础。
1.文献研究
本论文详细地介绍了近年来对于高脂血症、调脂治疗和血脂康的中西医文献,主要分为三个大的方面和六个主要部分,分别是:高脂血症病因病机及辨证分型的研究进展、高脂血症的中医药治疗研究进展、高脂血症的发病机制和临床分型研究概况、现代医学对高脂血症的治疗研究进展、血脂康的药理和基础研究概况、血脂康的临床研究进展。纵观这些相关文献,主要有以下一些重要的认识。
中医对病因病机的认识是中医药治疗疾病的理论基础。高脂血症是现代医学的术语,中医学中并无高脂血症一词,尽管目前从事这一方向研究的学者专家非常之多,但是整个中医学界尚未对高脂血症的病理机制和临床辩证分型形成统一的认识。从辨病的角度,医家较多地将其归入“眩晕”、“胸痹”、“中风”、“血瘀”、“痰湿”等病证的范畴中;从辨证的角度,又较多归入痰浊和瘀血证;从脏腑辨证的角度,更多归于肝、脾、肾三脏。中医药治疗高脂血症目前主要有三种方式,分别是自拟方、经典方和中成药。自拟方中常见的中药是:泽泻、山楂、何首乌和丹参;经典方较为常见的是:半夏白术天麻汤、血府逐瘀汤、黄连温胆汤和补阳还五汤;中成药常用的是:血脂康、脂必妥等等。从西医的角度看,高脂血症的发生关键在于脂质代谢的紊乱,目前临床上常规使用的调脂药物主要有六类,分别是胆酸螯合树脂类、烟酸类、氯贝丁脂类、他汀类、贝特类和新作用机制药物。
血脂康主要就含有他汀类的成分-洛伐他汀。相关研究证实其除了良好的调脂作用外,还有全面的调脂外作用,包括:抑制动脉粥样硬化的形成、对血管内皮细胞功能的保护作用、对血管平滑肌细胞增殖迁移的抑制作用、对脂质在肝脏沉积的抑制作用和改善血液流变学的作用。并且通过文献研究确定了本研究的药物试验剂量和疗程。
2.临床研究
2.1病例选择门诊及住院高脂血症患者血脂水平满足以下标准者入选:①沉淀法测定血浆低密度脂蛋白(LDL-C)≥3.12(120mg/dl);②酶法测定血清总胆固醇(TC)≥5.20(200mg/dl);③沉淀法测定血浆高密度脂蛋白(HDL-C)＜0.91(35mg/dl)。
入选病例共300例,均为中国中医科学院望京医院心内科门诊及住院患者,根据《中药新药临床试验指导原则》中对高脂血症的中医证候分型标准分为五组,每组各60例。痰浊阻遏组:男37例,女23例,平均年龄49±11岁;脾肾阳虚组:男33例,女27例,平均年龄52±9岁;肝肾阴虚组:男36例,女24例,平均年龄48±10岁;阴虚阳亢组:男30例,女30例,平均年龄52±11岁;气滞血瘀组:男31例,女29例,平均年龄53±9岁。5组患者年龄、性别及血脂水平在统计学上无显著差异。
2.2方法入选病例口服血脂康胶囊(北大维信生物科技有限公司生产)进行治疗,每次0.6 g,早晚各1次,连续服用8周,治疗期间停用其他降脂药物。
2.3观察指标在正常饮食情况下,禁食12～14小时后抽取清晨静脉血检验。①血脂指标:测定治疗前、后的LDL-C、TC和HDL-C含量,计算总胆固醇/高密度脂蛋白(TC/HDL)比值;②中医辩证指标:根据患者的中医症状及其症状的严重程度确定治疗前后的中医证候积分。③用药安全性指标:测定治疗前后的肝功能、肾功能、肌酸磷酸激酶(CK)等生化指标。
2.4统计学处理各检测指标数据以均数士标准差((?)±s)表示。所有统计过程均用SPSS13.0软件处理,各组治疗前后比较采用t检验,各组组间比较采用F检验及q检验。P＜0.05为显著性差异。
2.5结果
(1)治疗前、后五组LDL-C水平的比较:与治疗前比痰浊阻遏组和气滞血瘀组治疗后指标下降最为显著(P均＜0.01),此两组间无明显差异(P＞0.05),并且明显优于其它三组(P均＜0.05);脾肾阳虚组、肝肾阴虚组和阴虚阳亢组治疗前后指标间亦均具有显著差异性(P均＜0.05),但此三组间比较无明显差异(P＞0.05)。
(2)治疗前、后五组总胆固醇/高密度脂蛋白(TC/HDL)比值的比较:与治疗前比痰浊阻遏组该比值下降最为明显(P＜0.01),并且明显优于其余四组(P均＜0.05);气滞血瘀组、阴虚阳亢组、肝肾阴虚组该比值的下降均具有显著性(P均＜0.05),但此三组间比较无显著差异(P＞0.05);脾肾阳虚组治疗前后该比值无差异(P＞0.05)。
(3)治疗前、后五组中医证候积分的比较:与治疗前比痰浊阻遏组证候积分下降最为显著(P＜0.01),并且明显优于其余四组(P均＜0.05);阴虚阳亢组和气滞血瘀组证候积分也均显著下降(P均＜0.05),这两组间比较差异不显著(P＞0.05);其余肝肾阴虚组、脾肾阳虚组两组的证候积分下降均不明显(P均＞0.05)。
(4)安全性指标:所有入选病例,在8周的治疗中和治疗后,未出现肝功能、肾功能和CK等生化指标异常的情况。
3.讨论
高脂血症(Hyperlipemia,HLP)作为一种人体脂质代谢异常的疾病,它极大地促进动脉粥样硬化的发生与发展,由此增加冠心病、脑卒中、肾动脉硬化、周围血管闭塞等重大疾病的发病率。在血脂指标中,目前研究认为LDL含量和TC/HDL比值是考察高脂血症重大危害性最科学合理的两个项目。因此,将它们作为衡量降脂疗效的考察指标就使本课题更加合理。血脂康是经高产Monacolins的红曲菌通过现代生物技术发酵而得到的特制红曲提取物,其富含羟甲基戊二酰辅酶A(HMG-CoA)还原酶抑制剂(洛伐他汀)、多种不饱和脂肪酸和人体必需氨基酸以及甾醇和少量黄酮等多种有效成分。通过对低密度脂蛋白胆固醇(LDL-C)基因多态性的研究已经明确,具有h1等位基因的高脂血症患者对血脂康的反应较差,而具有h2等位基因的患者对其的反应较好,这就从理论上证明了血脂康具有疗效差异性。同时,作为一种纯中药制剂,它就必然存在中药的性味归经特性,由此,从高脂血症不同中医证候分型的角度对其作用差异性进行研究也就更具有其合理性。目前中医界对高脂血症较为一致的认识是:肝脾肾不足是其发生最本质的病理基础,而痰浊、血瘀等病理产物则是其发生、发展、转归和预后的基本病理环节。而血脂康的主要成分是中药红曲,它具有消痰化瘀、健脾和胃之功效,和该药物中的其他辅助成分相配合,就能做到攻中有补、标本兼顾,从而达到加强健脾消食而使痰瘀不生的目的。本次研究可以看出血脂康对痰浊阻遏组的各项治疗效果均是非常显著的,其次对于气滞血瘀组的综合疗效也是显著的;而相对于脾肾阳虚组疗效是最差的。存在这种证型疗效的差异可能是由于从中医理论上未能达到证法方药的高度统一的结果。联系上述的基因多态性研究,还可以进一步探讨属于中医痰浊阻遏证和气滞血瘀证的患者是否更多具有h2等位基因,而属于脾肾阳虚证的患者则更多具有h1等位基因。
4.结论
血脂康是一种有效成分明确,作用机制清楚,疗效稳定,安全有效,毒副作用小的纯天然中药。运用血脂康进行降脂治疗高脂血症患者,能够显著降低患者血脂水平,但存在证型疗效差异,其中痰浊阻遏组综合疗效最好,而脾肾阳虚组疗效则最不明显。在其临床运用中将它的作用差异性加以考虑,就能够真正做到用药科学合理,临床疗效亦会更加理想。
Hyperlipemia(HLP), as a model of abnormal lipid hypermetabolism of human body, is a kind of cardiovascular system disease which is very harm to human body, and its primary clinical symptom is that the blood fat level of blood plasma is abnormal. Now according to the research on HLP of every country, we have realized that HLP could make artherosclerosis occur early and accelerate its development, and the incidence of some important diseases such as incidence, cerebral apoplexy, renal arterial sclerosis, and peripheral vessels sclerosis which are related to HLP is increasing. So the world attaches importance on treating HLP, then exploitation and clinical research of many kinds of medicine to HLP is in the ascendant. XueZhiKang capsule(XZK) is a kind of pure Chinese drugs preparation which is widespread used, and its positive curative effect to lower blood lipid is to be proved, but in the clinical practice we can see that different patients of HLP who are treated with XZK have different curative effect. So we design this topic to observe the clinical effect of different types of syndromes of traditional Chinese medicine(TCM) in 300 patients of HLP treated with XZK, and full find out the variability of curative effect, then instruct clinical application more scientifically. The research is full of essentiality and signality.
Documents research
The rationale of TCM treating disease is the recognition of etiology and pathology. In TCM there is no disease called HLP, which is a modern medicinal terminology. At present many experts are researching on HLP, but there is no common knowledge about HLP on pathomechanism and syndrome differentiation in TCM.
From the point of view on disease differentiation, many doctors classify HLP to some diseases such as vertigo, thoracic obstruction, apoplexy, blood stasis, phlegmatic hygrosis, and so on. And from the point of view on syndrome differentiation, HLP belongs to Sputum stasis syndrome or blood stasis syndrome. Then from the point of view on differentiation of syndrome according to Zang-fu organs, HLP belongs to liver, spleen and kidney.
At present there are three kinds of methods on treating HLP. They are self working out prescription, classical prescription and Chinese patent medicine. Self working out prescription always contains alisma rhizome, hawthorn, fleeceflower root and salvia miltiorrhiza. And classical prescription may be Banxia Baizhu Tianma decoction, XueFuZhuYu decoction, Huanglian WenDan decoction and BuYangHuanWu decoction. Then Chinese patent medicine are always XZK and ZhiBiTuo.
Modern medicine thinks the key of pathogenesis in HLP is lipid metabolic disorder. Now there are 6 kinds of drugs which are common used clinically to regulate blood fat. They are cholic acid chelating resin, nicotinic acid, clofibrate, statins, fibrate and some drugs of new mechanism of action.
XZK contains a kind of statins calles lovastatin. And some related researches have proved that XZK could regulate blood fat, then it has all-sided functions except that such as inhibiting atherosclerotic to shape, protecting vascular endothelial cell function, inhibiting vascular smooth muscle cell to proliferate, inhibiting lipid deposite in liver, and improving hemorheological effect so on. So according to these documents we make a decision on this research on the test doses and course of treatment about XZK.
Clinical research
Cases selection:
The HLP patients who accepted clinic service or be in hospital whose blood fat levels were satisfied those standards could be selected. The standards contained:①blood plasma low density lipoprotein (LDL-C)≥3.12(120mg/dl) by precipitation;②blood serumtotal cholesterol(TC)≥5.20(200mg/dl) by enzymic method;③high density lipoprotein (HDL-C)< 0.91(35mg/dl) by precipitation。
According to the TCM syndrome differentiation of the book clinical research guide to new Chinese patent medicine, 2002 edition 300 patients of HLP were divided 5 groups, every groups have 60 patients. The five groups were the Sputum stasis syndrome group(37men, 23women, mean age 49±11), the Qi-stagnation induced Blood-stasis syndrome group(31men, 29women, mean age53±9), the Yin-deficiency and Yang-excessive group(30men, 30women, mean age52±11), the Hepatic and Renal Yin deficiency syndrome group(36men, 24women, mean age48±10) and Spleen-Yang deficiency and Kidney-Yang deficiency syndrome group(33men, 27women, mean age52±9). The five groups showed no significant difference in ages, sex and the level of blood fat.
Methods: All patients were treated with XZK. The dose was 0.6g at a time, Bid, n&m. The course of treatment was 8 weeks. During the course all drugs to lower blood fat should be prohibited. Changes of index of blood fat and TCM syndrome integral were observed after treatment.
Observed index:At the normal diet condition, abstract early morning venous blood venous blood after empty stomach for 12～14 hours.①Test the level of LDL-C, TC and HDL-C and the ratio of TC/HDL before and after treatment.②According to the levels of symptoms in TCM before and after treatment, account the TCM syndrome integral.③Observe biochemical indicators before and after treatment, such as liver function, renal function and CK.
Study methods:All data of the observed indexs was showed by x±s. During the statistical course, use t-check before and after treatment in the group, use F-check or q-check groupcomparison. And all of these was treated statistically by SPSS13.0 software. At P < 0.05, itshowed significant difference.
Results:
(1) After 8 weeks, the LDL-C of all groups were lower than before treatment(P<0.01, P<0.05).And the groups of Sputum stasis syndrome and Qi-stagnation induced Blood-stasis syndromewere superior to the three others(P <0.01), and the two groups showed on significant difference.
(2)The TC/HDL-C of Sputum stasis syndrome group was lowest in all groups (P<0.01)andsuperior to other groups (P<0.05); the Qi-stagnation induced Blood-stasis, Yin-deficiency andYang-excessive and Hepatic and Renal Yin deficiency syndrome group showed significantdifference in TC/HDL-C (P<0.05); and the Spleen-Yang Deficiency and Kidney-YangDeficiency syndrome group had no significant difference (P>0.05).
(3)The TCM syndrome integral of sputum stasis, yin-deficiency and yang-excessive, andqi-stagnation induced blood-stasis syndrome group were lower than before treatment (P<0.01,P<0.05), but the two other groups showed no significant difference (P>0.05), and the sputumstasis syndrome group was superior to the four other groups (P<0.05).
(4)During the treating course, all patients were no abnormal in liver function, renal function andCK.
Discussion
HLP, as a kind of abnormal lipid hypermetabolism disease, could make artherosclerosis occur early and accelerate its development, and the incidence of some important diseases such as incidence, cerebral apoplexy, renal arterial sclerosis and peripheral vessels sclerosis which are related to HLP is increasing. Now many experts think that two scientific and rational indexes for observing the great hazardness of HLP are the level of LDL and ratio of TC/HDL. So in this research the two indexes were used to weigh the fact about regulating blood fat.
XZK is an extract from productive monascus fermentation used by modern biotechnology, its active ingredients are full of HMG-CoA reducing enzyme inhibitor(lovastatin), many kinds of unsaturated fatty acid and unsaturated fatty acid for human body, some unsaturated fatty acid and a little of anthoxanthin. From the research on gene polymorphism of LDL-C, it was showed that the patients of HLP who had the h1 polymorphism were responded badly to XZK, but who had h1 polymorphism were well responded to it. In the research it showed that the curative effect variability was exacted.
As a pure Chinese drugs preparation, XZK has characteristics of nature and flavour and meridian distribution about Chinese drugs. It is rational to do this research on effective variability about XZK from the point of view on TCM syndrome differentiation.
At present the common knowledge about HLP is that the most essential patho-base is liver, spleen and kidney deficiency, and patho-products like sputum, and blood stasis are patho-links about occurring, development, turnover and prognosis.
The essential component of XZK is red rice, which has the function of eliminating blood stasis and phlegm and fortifying spleen and harmonizing stomach. When combined with the helper constituents, XZK could play the role of attacking and invigorating or dealing with both symptoms and body resistance, so it could fortify spleen and harmonize stomach, then eliminate blood stasis and phlegm.
In the research, XZK could regulate the level of blood fat, but the differentiation of syndrome types had existed. After treatment, the Sputum stasis syndrome group had the best effect, the Qi-stagnation induced Blood-stasis group had good effect, but the Spleen-Yang Deficiency and Kidney-Yang Deficiency syndrome type had no significant difference. Maybe the reason was that the syndrome didn't unified the methods from TCM theory. From the gene polymorphism research, maybe the reason was that the Sputum stasis syndrome group and the Qi-stagnation induced Blood-stasis group had h2 polymorphism, but the Spleen-Yang
Deficiency and Kidney-Yang Deficiency syndrome group had h1 polymorphism.
Conclusions :To sum up, XZK is a pure natural traditional Chinese drug, it has clear active ingredient, certain mechanism of action, stable curative effect, safe and effective, little toxic action and fewer side effects. After treatment there are best effect on the Sputum stasis syndrome group, then the he Spleen-Yang Deficiency and Kidney-Yang Deficiency syndrome type has no significant difference. If take its effect variability into account in clinic, you can really use medicine scientifically and rationally, then clinical curative effect can be more perfect.
1.文献研究
本论文详细地介绍了近年来对于高脂血症、调脂治疗和血脂康的中西医文献,主要分为三个大的方面和六个主要部分,分别是:高脂血症病因病机及辨证分型的研究进展、高脂血症的中医药治疗研究进展、高脂血症的发病机制和临床分型研究概况、现代医学对高脂血症的治疗研究进展、血脂康的药理和基础研究概况、血脂康的临床研究进展。纵观这些相关文献,主要有以下一些重要的认识。
中医对病因病机的认识是中医药治疗疾病的理论基础。高脂血症是现代医学的术语,中医学中并无高脂血症一词,尽管目前从事这一方向研究的学者专家非常之多,但是整个中医学界尚未对高脂血症的病理机制和临床辩证分型形成统一的认识。从辨病的角度,医家较多地将其归入“眩晕”、“胸痹”、“中风”、“血瘀”、“痰湿”等病证的范畴中;从辨证的角度,又较多归入痰浊和瘀血证;从脏腑辨证的角度,更多归于肝、脾、肾三脏。中医药治疗高脂血症目前主要有三种方式,分别是自拟方、经典方和中成药。自拟方中常见的中药是:泽泻、山楂、何首乌和丹参;经典方较为常见的是:半夏白术天麻汤、血府逐瘀汤、黄连温胆汤和补阳还五汤;中成药常用的是:血脂康、脂必妥等等。从西医的角度看,高脂血症的发生关键在于脂质代谢的紊乱,目前临床上常规使用的调脂药物主要有六类,分别是胆酸螯合树脂类、烟酸类、氯贝丁脂类、他汀类、贝特类和新作用机制药物。
血脂康主要就含有他汀类的成分-洛伐他汀。相关研究证实其除了良好的调脂作用外,还有全面的调脂外作用,包括:抑制动脉粥样硬化的形成、对血管内皮细胞功能的保护作用、对血管平滑肌细胞增殖迁移的抑制作用、对脂质在肝脏沉积的抑制作用和改善血液流变学的作用。并且通过文献研究确定了本研究的药物试验剂量和疗程。
2.临床研究
2.1病例选择门诊及住院高脂血症患者血脂水平满足以下标准者入选:①沉淀法测定血浆低密度脂蛋白(LDL-C)≥3.12(120mg/dl);②酶法测定血清总胆固醇(TC)≥5.20(200mg/dl);③沉淀法测定血浆高密度脂蛋白(HDL-C)＜0.91(35mg/dl)。
入选病例共300例,均为中国中医科学院望京医院心内科门诊及住院患者,根据《中药新药临床试验指导原则》中对高脂血症的中医证候分型标准分为五组,每组各60例。痰浊阻遏组:男37例,女23例,平均年龄49±11岁;脾肾阳虚组:男33例,女27例,平均年龄52±9岁;肝肾阴虚组:男36例,女24例,平均年龄48±10岁;阴虚阳亢组:男30例,女30例,平均年龄52±11岁;气滞血瘀组:男31例,女29例,平均年龄53±9岁。5组患者年龄、性别及血脂水平在统计学上无显著差异。
2.2方法入选病例口服血脂康胶囊(北大维信生物科技有限公司生产)进行治疗,每次0.6 g,早晚各1次,连续服用8周,治疗期间停用其他降脂药物。
2.3观察指标在正常饮食情况下,禁食12～14小时后抽取清晨静脉血检验。①血脂指标:测定治疗前、后的LDL-C、TC和HDL-C含量,计算总胆固醇/高密度脂蛋白(TC/HDL)比值;②中医辩证指标:根据患者的中医症状及其症状的严重程度确定治疗前后的中医证候积分。③用药安全性指标:测定治疗前后的肝功能、肾功能、肌酸磷酸激酶(CK)等生化指标。
2.4统计学处理各检测指标数据以均数士标准差((?)±s)表示。所有统计过程均用SPSS13.0软件处理,各组治疗前后比较采用t检验,各组组间比较采用F检验及q检验。P＜0.05为显著性差异。
2.5结果
(1)治疗前、后五组LDL-C水平的比较:与治疗前比痰浊阻遏组和气滞血瘀组治疗后指标下降最为显著(P均＜0.01),此两组间无明显差异(P＞0.05),并且明显优于其它三组(P均＜0.05);脾肾阳虚组、肝肾阴虚组和阴虚阳亢组治疗前后指标间亦均具有显著差异性(P均＜0.05),但此三组间比较无明显差异(P＞0.05)。
(2)治疗前、后五组总胆固醇/高密度脂蛋白(TC/HDL)比值的比较:与治疗前比痰浊阻遏组该比值下降最为明显(P＜0.01),并且明显优于其余四组(P均＜0.05);气滞血瘀组、阴虚阳亢组、肝肾阴虚组该比值的下降均具有显著性(P均＜0.05),但此三组间比较无显著差异(P＞0.05);脾肾阳虚组治疗前后该比值无差异(P＞0.05)。
(3)治疗前、后五组中医证候积分的比较:与治疗前比痰浊阻遏组证候积分下降最为显著(P＜0.01),并且明显优于其余四组(P均＜0.05);阴虚阳亢组和气滞血瘀组证候积分也均显著下降(P均＜0.05),这两组间比较差异不显著(P＞0.05);其余肝肾阴虚组、脾肾阳虚组两组的证候积分下降均不明显(P均＞0.05)。
(4)安全性指标:所有入选病例,在8周的治疗中和治疗后,未出现肝功能、肾功能和CK等生化指标异常的情况。
3.讨论
高脂血症(Hyperlipemia,HLP)作为一种人体脂质代谢异常的疾病,它极大地促进动脉粥样硬化的发生与发展,由此增加冠心病、脑卒中、肾动脉硬化、周围血管闭塞等重大疾病的发病率。在血脂指标中,目前研究认为LDL含量和TC/HDL比值是考察高脂血症重大危害性最科学合理的两个项目。因此,将它们作为衡量降脂疗效的考察指标就使本课题更加合理。血脂康是经高产Monacolins的红曲菌通过现代生物技术发酵而得到的特制红曲提取物,其富含羟甲基戊二酰辅酶A(HMG-CoA)还原酶抑制剂(洛伐他汀)、多种不饱和脂肪酸和人体必需氨基酸以及甾醇和少量黄酮等多种有效成分。通过对低密度脂蛋白胆固醇(LDL-C)基因多态性的研究已经明确,具有h1等位基因的高脂血症患者对血脂康的反应较差,而具有h2等位基因的患者对其的反应较好,这就从理论上证明了血脂康具有疗效差异性。同时,作为一种纯中药制剂,它就必然存在中药的性味归经特性,由此,从高脂血症不同中医证候分型的角度对其作用差异性进行研究也就更具有其合理性。目前中医界对高脂血症较为一致的认识是:肝脾肾不足是其发生最本质的病理基础,而痰浊、血瘀等病理产物则是其发生、发展、转归和预后的基本病理环节。而血脂康的主要成分是中药红曲,它具有消痰化瘀、健脾和胃之功效,和该药物中的其他辅助成分相配合,就能做到攻中有补、标本兼顾,从而达到加强健脾消食而使痰瘀不生的目的。本次研究可以看出血脂康对痰浊阻遏组的各项治疗效果均是非常显著的,其次对于气滞血瘀组的综合疗效也是显著的;而相对于脾肾阳虚组疗效是最差的。存在这种证型疗效的差异可能是由于从中医理论上未能达到证法方药的高度统一的结果。联系上述的基因多态性研究,还可以进一步探讨属于中医痰浊阻遏证和气滞血瘀证的患者是否更多具有h2等位基因,而属于脾肾阳虚证的患者则更多具有h1等位基因。
4.结论
血脂康是一种有效成分明确,作用机制清楚,疗效稳定,安全有效,毒副作用小的纯天然中药。运用血脂康进行降脂治疗高脂血症患者,能够显著降低患者血脂水平,但存在证型疗效差异,其中痰浊阻遏组综合疗效最好,而脾肾阳虚组疗效则最不明显。在其临床运用中将它的作用差异性加以考虑,就能够真正做到用药科学合理,临床疗效亦会更加理想。
Hyperlipemia(HLP), as a model of abnormal lipid hypermetabolism of human body, is a kind of cardiovascular system disease which is very harm to human body, and its primary clinical symptom is that the blood fat level of blood plasma is abnormal. Now according to the research on HLP of every country, we have realized that HLP could make artherosclerosis occur early and accelerate its development, and the incidence of some important diseases such as incidence, cerebral apoplexy, renal arterial sclerosis, and peripheral vessels sclerosis which are related to HLP is increasing. So the world attaches importance on treating HLP, then exploitation and clinical research of many kinds of medicine to HLP is in the ascendant. XueZhiKang capsule(XZK) is a kind of pure Chinese drugs preparation which is widespread used, and its positive curative effect to lower blood lipid is to be proved, but in the clinical practice we can see that different patients of HLP who are treated with XZK have different curative effect. So we design this topic to observe the clinical effect of different types of syndromes of traditional Chinese medicine(TCM) in 300 patients of HLP treated with XZK, and full find out the variability of curative effect, then instruct clinical application more scientifically. The research is full of essentiality and signality.
Documents research
The rationale of TCM treating disease is the recognition of etiology and pathology. In TCM there is no disease called HLP, which is a modern medicinal terminology. At present many experts are researching on HLP, but there is no common knowledge about HLP on pathomechanism and syndrome differentiation in TCM.
From the point of view on disease differentiation, many doctors classify HLP to some diseases such as vertigo, thoracic obstruction, apoplexy, blood stasis, phlegmatic hygrosis, and so on. And from the point of view on syndrome differentiation, HLP belongs to Sputum stasis syndrome or blood stasis syndrome. Then from the point of view on differentiation of syndrome according to Zang-fu organs, HLP belongs to liver, spleen and kidney.
At present there are three kinds of methods on treating HLP. They are self working out prescription, classical prescription and Chinese patent medicine. Self working out prescription always contains alisma rhizome, hawthorn, fleeceflower root and salvia miltiorrhiza. And classical prescription may be Banxia Baizhu Tianma decoction, XueFuZhuYu decoction, Huanglian WenDan decoction and BuYangHuanWu decoction. Then Chinese patent medicine are always XZK and ZhiBiTuo.
Modern medicine thinks the key of pathogenesis in HLP is lipid metabolic disorder. Now there are 6 kinds of drugs which are common used clinically to regulate blood fat. They are cholic acid chelating resin, nicotinic acid, clofibrate, statins, fibrate and some drugs of new mechanism of action.
XZK contains a kind of statins calles lovastatin. And some related researches have proved that XZK could regulate blood fat, then it has all-sided functions except that such as inhibiting atherosclerotic to shape, protecting vascular endothelial cell function, inhibiting vascular smooth muscle cell to proliferate, inhibiting lipid deposite in liver, and improving hemorheological effect so on. So according to these documents we make a decision on this research on the test doses and course of treatment about XZK.
Clinical research
Cases selection:
The HLP patients who accepted clinic service or be in hospital whose blood fat levels were satisfied those standards could be selected. The standards contained:①blood plasma low density lipoprotein (LDL-C)≥3.12(120mg/dl) by precipitation;②blood serumtotal cholesterol(TC)≥5.20(200mg/dl) by enzymic method;③high density lipoprotein (HDL-C)< 0.91(35mg/dl) by precipitation。
According to the TCM syndrome differentiation of the book clinical research guide to new Chinese patent medicine, 2002 edition 300 patients of HLP were divided 5 groups, every groups have 60 patients. The five groups were the Sputum stasis syndrome group(37men, 23women, mean age 49±11), the Qi-stagnation induced Blood-stasis syndrome group(31men, 29women, mean age53±9), the Yin-deficiency and Yang-excessive group(30men, 30women, mean age52±11), the Hepatic and Renal Yin deficiency syndrome group(36men, 24women, mean age48±10) and Spleen-Yang deficiency and Kidney-Yang deficiency syndrome group(33men, 27women, mean age52±9). The five groups showed no significant difference in ages, sex and the level of blood fat.
Methods: All patients were treated with XZK. The dose was 0.6g at a time, Bid, n&m. The course of treatment was 8 weeks. During the course all drugs to lower blood fat should be prohibited. Changes of index of blood fat and TCM syndrome integral were observed after treatment.
Observed index:At the normal diet condition, abstract early morning venous blood venous blood after empty stomach for 12～14 hours.①Test the level of LDL-C, TC and HDL-C and the ratio of TC/HDL before and after treatment.②According to the levels of symptoms in TCM before and after treatment, account the TCM syndrome integral.③Observe biochemical indicators before and after treatment, such as liver function, renal function and CK.
Study methods:All data of the observed indexs was showed by x±s. During the statistical course, use t-check before and after treatment in the group, use F-check or q-check groupcomparison. And all of these was treated statistically by SPSS13.0 software. At P < 0.05, itshowed significant difference.
Results:
(1) After 8 weeks, the LDL-C of all groups were lower than before treatment(P<0.01, P<0.05).And the groups of Sputum stasis syndrome and Qi-stagnation induced Blood-stasis syndromewere superior to the three others(P <0.01), and the two groups showed on significant difference.
(2)The TC/HDL-C of Sputum stasis syndrome group was lowest in all groups (P<0.01)andsuperior to other groups (P<0.05); the Qi-stagnation induced Blood-stasis, Yin-deficiency andYang-excessive and Hepatic and Renal Yin deficiency syndrome group showed significantdifference in TC/HDL-C (P<0.05); and the Spleen-Yang Deficiency and Kidney-YangDeficiency syndrome group had no significant difference (P>0.05).
(3)The TCM syndrome integral of sputum stasis, yin-deficiency and yang-excessive, andqi-stagnation induced blood-stasis syndrome group were lower than before treatment (P<0.01,P<0.05), but the two other groups showed no significant difference (P>0.05), and the sputumstasis syndrome group was superior to the four other groups (P<0.05).
(4)During the treating course, all patients were no abnormal in liver function, renal function andCK.
Discussion
HLP, as a kind of abnormal lipid hypermetabolism disease, could make artherosclerosis occur early and accelerate its development, and the incidence of some important diseases such as incidence, cerebral apoplexy, renal arterial sclerosis and peripheral vessels sclerosis which are related to HLP is increasing. Now many experts think that two scientific and rational indexes for observing the great hazardness of HLP are the level of LDL and ratio of TC/HDL. So in this research the two indexes were used to weigh the fact about regulating blood fat.
XZK is an extract from productive monascus fermentation used by modern biotechnology, its active ingredients are full of HMG-CoA reducing enzyme inhibitor(lovastatin), many kinds of unsaturated fatty acid and unsaturated fatty acid for human body, some unsaturated fatty acid and a little of anthoxanthin. From the research on gene polymorphism of LDL-C, it was showed that the patients of HLP who had the h1 polymorphism were responded badly to XZK, but who had h1 polymorphism were well responded to it. In the research it showed that the curative effect variability was exacted.
As a pure Chinese drugs preparation, XZK has characteristics of nature and flavour and meridian distribution about Chinese drugs. It is rational to do this research on effective variability about XZK from the point of view on TCM syndrome differentiation.
At present the common knowledge about HLP is that the most essential patho-base is liver, spleen and kidney deficiency, and patho-products like sputum, and blood stasis are patho-links about occurring, development, turnover and prognosis.
The essential component of XZK is red rice, which has the function of eliminating blood stasis and phlegm and fortifying spleen and harmonizing stomach. When combined with the helper constituents, XZK could play the role of attacking and invigorating or dealing with both symptoms and body resistance, so it could fortify spleen and harmonize stomach, then eliminate blood stasis and phlegm.
In the research, XZK could regulate the level of blood fat, but the differentiation of syndrome types had existed. After treatment, the Sputum stasis syndrome group had the best effect, the Qi-stagnation induced Blood-stasis group had good effect, but the Spleen-Yang Deficiency and Kidney-Yang Deficiency syndrome type had no significant difference. Maybe the reason was that the syndrome didn't unified the methods from TCM theory. From the gene polymorphism research, maybe the reason was that the Sputum stasis syndrome group and the Qi-stagnation induced Blood-stasis group had h2 polymorphism, but the Spleen-Yang
Deficiency and Kidney-Yang Deficiency syndrome group had h1 polymorphism.
Conclusions :To sum up, XZK is a pure natural traditional Chinese drug, it has clear active ingredient, certain mechanism of action, stable curative effect, safe and effective, little toxic action and fewer side effects. After treatment there are best effect on the Sputum stasis syndrome group, then the he Spleen-Yang Deficiency and Kidney-Yang Deficiency syndrome type has no significant difference. If take its effect variability into account in clinic, you can really use medicine scientifically and rationally, then clinical curative effect can be more perfect.
引文
1.赵水平主编.临床血脂学[M].第三版.长沙:湖南科学技术出版社,1997:7-9
2.孙丽英,焦亚斌,康广盛.高脂血症的病因病机研究进展[J].中医药学报,2004,32(2):70-71
3.孙天福,马仁生.袁海波教授治疗高脂血症学术思想及经验[J].中医研究,2004,17(2):41-44
4.佟丽娟.高脂血症的病因病机及辨证分型治疗[J].中医药学刊,2002,20(2):244-244
5.叶任高,陆再英.内科学[M].第五版.北京:人民卫生出版社,2001:832-840
6.陈灏珠.实用内科学[M].第10版.北京:人民卫生出版社,1997:878-879
7.金永娟,李宏妹.高血脂对血细胞和血管内皮细胞的损伤[J].中国微循环,2002,2(6):221
8.寇文镕.血脂康基础与临床研究概述[J].中华内科杂志,1998,37(6):364-366
9.秦树存,王士雯.低密度脂蛋白受体基因多态性对血脂康调脂疗效的影响[J].解放军医学杂志,1999,24(4):271
10.林来胜.中医对高脂血症的认识及治疗探讨[J].陕西中医,2001,22(2):94-95
11.熊文生,曾益宏,刘友章,等.理脾化痰降脂片治疗老年高脂血症140例疗效观察[J].新中医,2000,32(7):16-18
12.屈松柏主编.实用中医心血管病学[M].第1版.北京:科学技术文献出版社,1993:291
13.徐育珊.论高脂血症的标本兼治[J].江苏中医,1997,18(11):11
14.韩淑亚,张笑峥.高脂血症病因病机研究进展[J].甘肃中医,2001,14(3):88-90
15.庞剑,杜文斌,周学文.高脂血症的中西医研究集析[J].中医药学刊,2003,21(12):2124-2125
16.关宝莲,齐红羽.高脂血症的中医辨证分型研究[J].山西中医,2005,21(1):41-42
17.宋晓芳.辨证分型治疗高脂血症82例疗效分析[J].中医药学刊,2001,19(5):478-479
18.屠浩明.高脂血症血脂水平与中医辨证分型的相关性研究[J].福建中医药,2003,34(6):3-4
19.唐荣德,罗治华.高脂血症血脂和凝血因子与脏腑及气血津液证型的关系探讨[J].中西医结合心脑血管病杂志,2005,3(3):193-195
20.刘明,魏丹霞.急性心肌梗死患者血脂水平变化与中医辨证分型的临床研究[J].中国中西医结合急救杂志,2001,8(1):29-30
21.雷义举.中医辨证治疗高脂血症82例[J].陕西中医,2002,23(6):507-508
22.任勇才.辨证分型治疗高脂血症38例报告[J].右江民族医学院学报,2004,26(4):602
23.黄承才,高旭让,范玉坤,等.化脂灵治疗高脂血症的临床研究[J].实用中西医杂志,1998,11(2):101-103
24.孙立,陈利国,郑仕副,等.益寿调脂片对原发性高脂血症患者脂质调节及中医辨证分型的影响[J].山东中医杂志,2003,22(2):77-80
25.邱李华,郝建军,关朝红.红曲制剂治疗高脂血症112例观察[J].中国民间疗法,1997,6:34
26.于克娇月旨必妥治疗中医不同证型高脂血症的临床观察.福建中医学院2001年硕士论文,2001:17
27.邹春阳.106例冠脉造影患者血脂及血液流变学指标分析[J].临床内科学杂志,1996,16(4):31
28.牛丽丽.冠心病患者血管内皮细胞损伤血管活性物质失衡对冠脉的调控作用[J].解放军医学杂志,1996,21(4):283
29.费宇行.冠心病、高血压病人血脂及载脂蛋白的临床研究[J].解放军医学杂志,1996.21(5):368
30.赵水平.降脂药物临床运用评价[J].CHINA MEDICAL NEWS,2006,21(8):22
31.李建军.他汀类药物治疗急性冠脉综合征的抗炎机制[J].临床杂志,2006,23(1):8-11
32.胡大一.ACC2006热点报道[J].CHINA MEDICAL NEWS,2006,21(8):5
33.胡大一.美国心脏协会学术年会2005热点报道[J].中华心血管病杂志,2006,34(2):184-186
34.赵水平.降血脂药物国外研发的现状[J].中国医药技术与场,2006,6(2):54-56
35.寇文镕血脂康基础与临床研究概述[J].中华内科杂志,1998,37(6):364-366
36.张传海,苏美庆.血脂康的药理与临床研究进展[J].河北医药,2004,26(11):911-912
37.寇文镕.血脂康基础与临床研究现况概述[J].中国处方药,2005,62(6):62
38.周玉芳,张茂良.特制医用调脂红曲的制备和药用价值[J].中国中医基础医学杂志,2000,6(3):37-38
39.徐艳春,魏璐雪.红曲及其制剂血脂康中磷脂酰胆碱的含量测定[J].中国中药杂志,2000,25(12):720-721
40.李鹏,陈兰英.血脂康抑制猪肝HMGCoA还原酶的能力[J].基础医学与临床,2003,23(5):531-534
41.王晓静,曾定尹,丁峰等.血脂康对实验性家兔动脉粥样硬化形成及其脂质过氧化损伤的影响[J].中国循环杂志,1998,13(5):305-307
42.王丽.红曲提取物对肾病综合征血清脂谱和肾小球硬化的影响[J].中国中西医结合肾病志,2000,1(3):154-156
43.张鹏华.血脂康在体外对巨噬细胞分泌基质金属蛋白酶-2的抑制作用[J].中华心血管病杂志,2001,29(8):497-499
44.徐伯平.血脂康及氧化低密度脂蛋白对牛血管平滑肌细胞增殖的影响[J].中华老年医学杂志,2001,20(5):384-385
45.徐伯平.血脂康对鼠巨噬细胞摄取氧化低密度脂蛋白能力的影响[J].世界医学杂志,2000,(6):131
46.王银叶.特种红曲对鹌鹑实验性脂肪肝的治疗作用[J].中国临床药理学与治疗学,2002,7(4):293-295
47.齐国先.血脂康对家兔血管成形术后内膜增殖及内皮功能的影响[J].中国循环杂志,1999,14增刊:231
48.齐国先.血脂康对家兔血管成形术后内膜增殖及C-myc基因表达的影响[J].中华内科杂志,1999,38(8):514-516
49.吴伟.血脂康对血脂和血管内皮细胞活性物质的影响[J].中国动脉硬化杂志,2003,11(5):419-423
50.郑广娟,张文高,孔岩玲等.血脂康对载脂蛋白E基因敲除小鼠动脉粥样硬化的影响[J].中国动脉硬化杂志,2003,11(5):408-410
51.孔岩玲,张文高,郑广娟.血脂康胶囊调节血管内皮分泌功能的临床与实验研究[J].新疆中医药,2006,24(2):38-40
52.张曼,佟英,郑晓伟,等.血脂康对家兔血脂及脂肪肝形成的影响[J].中华肝脏病杂志,2001,9(7增刊):341
53.徐伯平.血脂康对低密度脂蛋白体外氧化修饰的影响[J].中华内科杂志,1999,38(8):520-522
54.李正斌.血脂康对高脂血症德脂质过氧化作用的影响[J].首都医药,2000,7(3):42
55.俞虹,崔燕玲,吴永健,等.血脂康对冠心病并发高脂血症患者纤溶功能的影响[J].中国煤炭工业医学杂志,2002,5(1):61-62
56.吴永健,俞虹,崔燕玲.不同类型高脂血症小而密低密度脂蛋白的水平及调血脂治疗对其影响[J].中国循环杂志,2002,17(6):431-433
57.Shui-Ping Zhao,Ling Liu,et al.Effect of xuezhikang,a cholestin extract,on reflecting postprandial triglyceridemia after a high-fat meal in patients with coronary heart disease[J].Atherosclerosis,2003,168:375-380
58.王蔚.血脂康对颈动脉斑块的影响[J].中国临床药学杂志,2002,11(5):263-265
59.吴济荫.血脂康降低高脂血症患者血清可溶性粘附分子含量的观察[J].兰州医学院学报,2003,26(4):10-12
60.王锋,朱川.血脂康对血脂异常患者C-反应蛋白的影响[J].广州医药,2003,33(5)5:32-33
61.Ling Liu,Shui-Ping Zhao,et al.Xuezhikang decreases serum lipoprotein(a) and C-reactive protein concentrations in patients with coronary heart diease[J].Clinical Chemistry,2003,49(8):1347-1352
62.蔡树霞,孙薇.血脂康对高脂血症患者血小板活性及纤溶活性的影响[J].山东医药,2003,43(28):6-8
63.吕春华.血脂康对2型糖尿病糖、脂代谢及血小板活化功能的影响[J].广西医学,2003,25(1):16-18
64.江劲波.血脂康对高脂血症患者血脂谱的作用和对血栓素A2与前列环素的影响[J].中华内科杂志,1999,38(8):517
65.王曦云,盛莉.洛伐他汀治疗冠心病高胆固醇血症对血管内皮功能微循环及胰岛素敏感性的影响[J].中国实用内科杂志,2003,23(11):660-662
66.赵志明,王毅.血脂康对正常胆固醇水平不稳定性心绞痛患者血管内皮依赖性舒张功能的影响[J].中国中西医结合杂志,1999,19(11):38-40
67.程训民,余宗梅.血脂康对高脂血症患者血管内皮功能的影响[J].中国动脉硬化杂志,2001,9(3):235-237
68.杨海波,唐元升.血脂康对高脂血症患者内皮功能及血中一氧化氮与内皮素水平的影响[J].中国中西医结合杂志,2003,23(1):13-15
69.魏炜,李仁立.血浆高甘油三酯对老年人血管内皮功能的损害及血脂康的修复作用[J].临床心血管病杂志,2002,18(7):336-337
70.吴永健,俞虹.血脂康对冠心病合并高脂血症患者血管内皮细胞的保护作用[J].中华老年心脑血管病杂志,2002,4(5):319-321
71.程艳春,赵水平.调脂治疗对冠心病患者餐后血管内皮功能的影响[J].中华心血管病杂志,2004, 32(2):114-117
72.陈建国,徐伯平.血脂康对老年陈旧性心肌梗塞患者氧化修饰低密度脂蛋白及血管内皮功能的影响[J].南京医科大学学报,2001,21(4):322-324
73.李国平,欧阳淼.血脂康降脂作用与血清一氧化氮关系的研究[J].临床心血管病杂志,2002,18(4):169-170
74.王曦云,盛莉.洛伐他汀治疗冠心病高胆固醇血症对血管内皮功能微循环及胰岛素敏感性的影响[J].中国实用内科杂志,2003,23(11):660-662
75.曾祥义,潘婕.血脂康对2型糖尿病合并高脂血症血管内皮细胞保护作用的临床观察[J].第三军医大学学报,2001,23(6):726-728
76.王景明,吕秀云.血脂康对高血压病患者左室功能及重构的影响[J].临床荟萃,2000,15(14):645-646
77.周宁,朱丽琼.血脂康对糖尿病甲皱微循环及血液流变学的影响[J].中华实用医学,2001,3(1):56-57
78.郑华,丹笑颖.血脂康改善血流变学及临床疗效观察[J].河北医学,2001,7(1):46-48
79.徐轶,魏群.血脂康胶囊治疗原发性高脂血症伴高粘血症50例疗效观察[J].河北中医,2000,22(7):525-526
80.张东翔,袁俊强,李玉杰.血脂康治疗高脂血症临床疗效观察[J].中华内科杂志,1998,37(6):4021
81.秦树存,张维强,赵美玲,等.随机双盲对照试验观察血脂康对老年高脂血症患者的临床功效[J].中华内科杂志,1998,37(6):4011
82.梁敬芝,伍春凤,姚盛思.血脂康治疗53例高脂血症临床分析[J].广西医学,2006,28(1):123
83.戴小华,卓秀珍.血脂康胶囊对不稳定性心绞痛患者血脂异常的影响[J].中药新药与临床药理,1999,10(4):68-69
84.邓洁,雷芸,彭春花.血脂康治疗急性心肌梗死伴高脂血症临床观察[J].首都医药,2000,7(1):42-43
85.王伟华,章辉喻,艳林葛,等.血脂康对不同血脂水平的急性冠状动脉综合征患者的干预作用[J].中国中西医结合杂志,2004,24(12):1073-1076
86.张戈,杨瑞丰,阮志敏,等.不同剂量血脂康调脂疗效的临床观察[J].中国实用内科杂志,2002,22(5):304-305
87.熊辉,胡琴,夏玲玲.不同剂量血脂康调脂疗效的研究[J].现代中西医结合杂志,2003,12(5):1577-1578
88.曾群英,麦炜颐,高修仁,等.2种剂量血脂康胶囊治疗高脂血症的临床研究[J].中国新药杂志,2002,11(3):229-232
89.Wang M,Shen JJ,Huang SE,et al.To compare the effects of different do Xuezhikang with prova statin on blood lipids and inflammatory factors in patients with acute coronary syndrome[J].Prey Treat Cardio Cereb Vasc Dis 2005,5(5):14-16
90.王文宏.血脂康和阿托伐他汀治疗高胆固醇血症的疗效比较[J].实用中医内科杂志,2006,20(3):305
91.LIU Zhi-gao,YU Xi-yong.Effects of Xuezhikang Capsule on Blood Lipids,Platelet Activation and Coagulation-Fibrinolysis Activity in Patients with Hyperlipidemia[J].C JIM,2004,10(4):257-262
92.王素如.血脂康与洛伐他汀治疗高脂血症的疗效比较[J].中国新药与临床杂志,2000,19(4):249-251.
93.张海,张言镇.血脂康和洛托伐他汀治疗原发性高脂血症对比研究[J].实用新医学,2002,(6):481-482.
94.席蓓莉.血脂康与辛伐他汀治疗老年原发性高脂血症疗效比较[J].上海第二医科大学学报,2002,22(3):285-286.
95.郑英,罗希芝,王树玲,等.血脂康与辛伐他汀临床疗效的对照研究[J].中国药学杂志,2001,36(10):715
96.孙瑞华.血脂康与辛伐他汀治疗高脂血症的比较[J].中国药学杂志,2001,36(10):715
97.陈凌,秦永文.血脂康胶囊治疗高胆固醇的临床效果[J].药学服务与研究,2002,2(1):39-40
98.李玉珊,雷华芝.血脂康治疗老年高脂血症41例临床观察[J].中国全科医学,2003,6(2):163
99.殷玲,张桂清,王淑芳.血脂康治疗高脂血症的临床观察[J].现代中西医结合杂志,2000,9(7):599-601
100.高雷山,廖勇.血脂康、来适可调节冠心病患者血脂疗效观察[J].现代中西医结合杂志,2003,12(23):25-28
101.申明月.血脂康和阿托伐他汀治疗高脂血症的疗效比较[J].中华医学实践杂志,2003,2(5):439-440
102.陆国平,霍淑钦,沈永初,等.血脂康和辛伐他汀对高胆固醇血症调脂作用的比较[J].中华内科杂志,1998,37(6):3711
103.金炜,杨红,张承,等.血脂康和美百乐镇对照治疗原发性高脂血症[J].中国新药杂志,1997,6(4):2651
104.金智敏,赵晓薇.血脂康与非诺贝特对高血压高危患者高脂血症的疗效对比研究[J].上海医药,2002,23(4):171-172
105.傅蓉蓉,李群血脂康治疗高脂血症[J].中国临床药学杂志,2000,9(4):243-244
106.王卫霞,陈可冀.血脂康胶囊治疗高脂血症有效性和安全性的系统评价[J].Chin J Evid-based Med,2006,Vol.6(5):352-358
107.王健,肖明英.血脂康联合小剂量阿司匹林治疗冠心病并高脂血症65例的长期疗效观察[J].新医学,2000,31(10):596-597
108.王爱娥,白根明.血脂康治疗冠心病心绞痛疗效观察[J].山西职工医学院学报,2003,13(1):23-24
109.陶钦洪,贾连旺.血脂康对老年冠心病患者血脂及血液流变学影响的观察[J].浙江临床医学,2005,7(12):1295-1296
110.薛连喜,藤雅轩.血脂康对冠心病并发高脂血症病人血管内皮功能及C反应蛋白的影响[J].中西医结合心脑血管病杂志,2006,4(6:477-478
111.XU Zhi-min.Effects of Xuezhikang Cap sule on High Risk Population in Chinese Coronary Secondary Prevention Study(CCSPS) and the Enlightenment from It[J].Chin J Integr Med,2006,12(2):87-89
112.方咏红,李卫.血脂康对2型糖尿病患者脂代谢及胰岛B细胞功能影响的研究[J].首都医药,2000, 7(2):44
113.王彩玲,李曙远,张伟.血脂康对2型糖尿病人胰岛素敏感性的影响[J].中国糖尿病杂志,2001,9(3):171-173
114.戴小华,薛晓阳,汪玲,等.血脂康对高血压病合并血脂异常胰岛素敏感性的影响[J].中国中西医结合杂志,2000年,20(9):692-693
115.王景明,崔群,吕秀云,等.血脂康治疗胰岛素抵抗的疗效观察[J].潍坊医学院学报,2002,24(1):50-51
116.林永丽,左晶,王虹,等.血脂康治疗2型糖尿病合并高脂血症80例临床观察[J].中国老年医学杂志,2000,20(4):243-244
117.周黎,邬玲.血脂康治疗糖尿病合并血脂异常的疗效观察[J].ACMP,2002,30(5):40
118.彭卫华,曲强,陈健.血脂康对合并高脂血症的非胰岛素依赖型糖尿病患者微量白蛋白尿的影响[J].中国中西医结合肾病杂志,2001,(21):46-47
119.姚颖,刘晓城.血脂康治疗肾病综合征30例疗效观察[J].中国全科医学,2002,5(3):244-245
120.王学彬,刘玉夏.血脂康治疗慢性肾功能衰竭腹膜透析病人高脂血症[J].滨州医学院学报,2003,26(6):430-431
121.香瑶英,霍丽娟.血脂康治疗脂肪肝临床疗效观察[J].中国肝脏病杂志,200l,9(增刊):92-93
122.刘娅,赵经川,刘虹.血脂康治疗276例脂肪肝B超声像图变化[J].中华内科杂志,1999,38(8):554-555
123.陈丽娟,徐薇.联合血脂康治疗脂肪肝的临床观察[J].中华临床医药,2003,4(10):24-25
124.毕迅.血脂康治疗脑梗塞伴高脂血症疗效观察[J].首都医药,2000,7(4):35
125.孙惠华.血脂康对高脂血症患者颈动脉内2中膜厚度的影响[J].中国基层医药,2006,13(2):339
126.田沈,王溪原,窦文波,等.血脂康治疗60例高脂血症并颈动脉斑块临床观察[J].临床内科杂志,2005,22(10):713
127.郝兵.血脂康治疗颈动脉粥样硬化疗效观察[J].辽宁中医杂志,2006,33(5):558
128.Kannel WB,Castelli WP,Gordon T.Cholesterol in the prediction of atherosclerotic disease.New perspectives based on the Framingham study.Ann Intern Med.1979,90:85-91
129.Hunninghake D,LaRosa JC,Bush D,et al.The cholesterol facts.A joint statement by the American Heart Association and the National Heart,Lung,and Blood institute[J].American Heart Association Circulation,1990,81:1721-1733
130.Wakugami K,Iseki K,Kimura Y,et al.Relationship between serum cholesterol and the risk of acute myocardial infarction in a screened cohort in Okinawa[J],Japan Jpn Circ J,1998,62:7-14
131.Chen Z,Peto R,Collins R,et al.Serum cholesterol concentration and coronary heart disease in population with low cholesterol concentration[J].BMJ,1991,3(3):267-282
132.Pearson TA,Laurora I,Chu H,et al.The lipid treatment assessment project(L-TAP):a-multicenter survey to evaluate the percentages of dyslipidemic patients receiving lipid-lowing therapy and achieving lowdensity lipoprotein cholesterol goals[J].Arch Intern Med,2000,160:459-467
133.Freuhauf S,Veldwijk MR,Kramer A,et al.Baseline serum cholesterol and treatment effect in the Scandinavian Simvastatin Survial Sutdy(4S)[J].Lancet,1995,345(89):1274-1275
134.Sacks FM,Pfeffer MA,Moye LA,et al.The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels[J].New England Med.1996,335:1001-1009
135.Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels.The Long-Term Intervention with Pravastatin in Ischaemic Disease(LIPID) Study Group[J].New England Med,1998,339:1349-1357
136.West of Scotland Coronary Prevention Study:implication for clinical practice.The WOSCOPS Study Group[J].Europe Heart 1996,17:163-164
137.Downs JR,Clearfield M,Weis S,et al.Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels:results of AFCAPS/TexCAPS.Air Force/Texas Coronary Atherosclerosis Prevention Study[J].JAMA,1998,279:1615-1622
138.杨宝峰,苏定冯.药理学[S].第六版.北京:人民卫生出版社,2003:282-283
139.Goldman,Bennett.Cecil Textbook of Medicine,21th edition.[M].北京:世界图书社,2003:16-17
140.Lea AP,Mc Tavish D.Atorvastatin,a review of its pharmacology and therapeutic potential in the management of hyperlipidaemias[J].Drugs,1997,53:828-847
141.Dean G.Compafison of efficacy and safety of atorvastatin and simvastatin in patients with dyslipidemia with and without coronary disease[J].Am J Cardio,2002,89:667-671
142.Dresser GK,Spence JD,Bailey DG,et al.Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition[J].Clin Pharmacolinet,2000,38(1):41
143.Foley KA,Massing MW,Simpson RJ,et al.The cholesterol ester transfer protein TaqlB gene polymorphism predicts clinical benefit of statin therapy in patients with significant coronary artery disease[J].Am Heart J 2003,146:1007-1014
144.陆纪宏.试论中医辨治高脂血症[J].辽宁中医杂志,1991,2:2
145.简亚平.高脂血症中医药研究近况述评[J].湖南中医学院学报,1999,19(1):62
146.吴松鹰,林求诚,杨持.老年脂质代谢紊乱中医医患因素临床调查[J].中国中西医结合杂志,1993,13(5):273
147.张继东,高洪春,李长华主编.心血管病当代中医治疗[M].第一版.济南:济南出版社,1996:115
148.宋剑南,刘东远,牛晓红,等.高脂血症与中医痰浊关系的实验研究[J].中国中医基础医学杂志,1995,1(1):49
149.俞亚琴,郭兮华.从血液流变学探讨高脂血症的痰湿改变[J].辽宁中医杂志,1995,22(6):241
2.孙丽英,焦亚斌,康广盛.高脂血症的病因病机研究进展[J].中医药学报,2004,32(2):70-71
3.孙天福,马仁生.袁海波教授治疗高脂血症学术思想及经验[J].中医研究,2004,17(2):41-44
4.佟丽娟.高脂血症的病因病机及辨证分型治疗[J].中医药学刊,2002,20(2):244-244
5.叶任高,陆再英.内科学[M].第五版.北京:人民卫生出版社,2001:832-840
6.陈灏珠.实用内科学[M].第10版.北京:人民卫生出版社,1997:878-879
7.金永娟,李宏妹.高血脂对血细胞和血管内皮细胞的损伤[J].中国微循环,2002,2(6):221
8.寇文镕.血脂康基础与临床研究概述[J].中华内科杂志,1998,37(6):364-366
9.秦树存,王士雯.低密度脂蛋白受体基因多态性对血脂康调脂疗效的影响[J].解放军医学杂志,1999,24(4):271
10.林来胜.中医对高脂血症的认识及治疗探讨[J].陕西中医,2001,22(2):94-95
11.熊文生,曾益宏,刘友章,等.理脾化痰降脂片治疗老年高脂血症140例疗效观察[J].新中医,2000,32(7):16-18
12.屈松柏主编.实用中医心血管病学[M].第1版.北京:科学技术文献出版社,1993:291
13.徐育珊.论高脂血症的标本兼治[J].江苏中医,1997,18(11):11
14.韩淑亚,张笑峥.高脂血症病因病机研究进展[J].甘肃中医,2001,14(3):88-90
15.庞剑,杜文斌,周学文.高脂血症的中西医研究集析[J].中医药学刊,2003,21(12):2124-2125
16.关宝莲,齐红羽.高脂血症的中医辨证分型研究[J].山西中医,2005,21(1):41-42
17.宋晓芳.辨证分型治疗高脂血症82例疗效分析[J].中医药学刊,2001,19(5):478-479
18.屠浩明.高脂血症血脂水平与中医辨证分型的相关性研究[J].福建中医药,2003,34(6):3-4
19.唐荣德,罗治华.高脂血症血脂和凝血因子与脏腑及气血津液证型的关系探讨[J].中西医结合心脑血管病杂志,2005,3(3):193-195
20.刘明,魏丹霞.急性心肌梗死患者血脂水平变化与中医辨证分型的临床研究[J].中国中西医结合急救杂志,2001,8(1):29-30
21.雷义举.中医辨证治疗高脂血症82例[J].陕西中医,2002,23(6):507-508
22.任勇才.辨证分型治疗高脂血症38例报告[J].右江民族医学院学报,2004,26(4):602
23.黄承才,高旭让,范玉坤,等.化脂灵治疗高脂血症的临床研究[J].实用中西医杂志,1998,11(2):101-103
24.孙立,陈利国,郑仕副,等.益寿调脂片对原发性高脂血症患者脂质调节及中医辨证分型的影响[J].山东中医杂志,2003,22(2):77-80
25.邱李华,郝建军,关朝红.红曲制剂治疗高脂血症112例观察[J].中国民间疗法,1997,6:34
26.于克娇月旨必妥治疗中医不同证型高脂血症的临床观察.福建中医学院2001年硕士论文,2001:17
27.邹春阳.106例冠脉造影患者血脂及血液流变学指标分析[J].临床内科学杂志,1996,16(4):31
28.牛丽丽.冠心病患者血管内皮细胞损伤血管活性物质失衡对冠脉的调控作用[J].解放军医学杂志,1996,21(4):283
29.费宇行.冠心病、高血压病人血脂及载脂蛋白的临床研究[J].解放军医学杂志,1996.21(5):368
30.赵水平.降脂药物临床运用评价[J].CHINA MEDICAL NEWS,2006,21(8):22
31.李建军.他汀类药物治疗急性冠脉综合征的抗炎机制[J].临床杂志,2006,23(1):8-11
32.胡大一.ACC2006热点报道[J].CHINA MEDICAL NEWS,2006,21(8):5
33.胡大一.美国心脏协会学术年会2005热点报道[J].中华心血管病杂志,2006,34(2):184-186
34.赵水平.降血脂药物国外研发的现状[J].中国医药技术与场,2006,6(2):54-56
35.寇文镕血脂康基础与临床研究概述[J].中华内科杂志,1998,37(6):364-366
36.张传海,苏美庆.血脂康的药理与临床研究进展[J].河北医药,2004,26(11):911-912
37.寇文镕.血脂康基础与临床研究现况概述[J].中国处方药,2005,62(6):62
38.周玉芳,张茂良.特制医用调脂红曲的制备和药用价值[J].中国中医基础医学杂志,2000,6(3):37-38
39.徐艳春,魏璐雪.红曲及其制剂血脂康中磷脂酰胆碱的含量测定[J].中国中药杂志,2000,25(12):720-721
40.李鹏,陈兰英.血脂康抑制猪肝HMGCoA还原酶的能力[J].基础医学与临床,2003,23(5):531-534
41.王晓静,曾定尹,丁峰等.血脂康对实验性家兔动脉粥样硬化形成及其脂质过氧化损伤的影响[J].中国循环杂志,1998,13(5):305-307
42.王丽.红曲提取物对肾病综合征血清脂谱和肾小球硬化的影响[J].中国中西医结合肾病志,2000,1(3):154-156
43.张鹏华.血脂康在体外对巨噬细胞分泌基质金属蛋白酶-2的抑制作用[J].中华心血管病杂志,2001,29(8):497-499
44.徐伯平.血脂康及氧化低密度脂蛋白对牛血管平滑肌细胞增殖的影响[J].中华老年医学杂志,2001,20(5):384-385
45.徐伯平.血脂康对鼠巨噬细胞摄取氧化低密度脂蛋白能力的影响[J].世界医学杂志,2000,(6):131
46.王银叶.特种红曲对鹌鹑实验性脂肪肝的治疗作用[J].中国临床药理学与治疗学,2002,7(4):293-295
47.齐国先.血脂康对家兔血管成形术后内膜增殖及内皮功能的影响[J].中国循环杂志,1999,14增刊:231
48.齐国先.血脂康对家兔血管成形术后内膜增殖及C-myc基因表达的影响[J].中华内科杂志,1999,38(8):514-516
49.吴伟.血脂康对血脂和血管内皮细胞活性物质的影响[J].中国动脉硬化杂志,2003,11(5):419-423
50.郑广娟,张文高,孔岩玲等.血脂康对载脂蛋白E基因敲除小鼠动脉粥样硬化的影响[J].中国动脉硬化杂志,2003,11(5):408-410
51.孔岩玲,张文高,郑广娟.血脂康胶囊调节血管内皮分泌功能的临床与实验研究[J].新疆中医药,2006,24(2):38-40
52.张曼,佟英,郑晓伟,等.血脂康对家兔血脂及脂肪肝形成的影响[J].中华肝脏病杂志,2001,9(7增刊):341
53.徐伯平.血脂康对低密度脂蛋白体外氧化修饰的影响[J].中华内科杂志,1999,38(8):520-522
54.李正斌.血脂康对高脂血症德脂质过氧化作用的影响[J].首都医药,2000,7(3):42
55.俞虹,崔燕玲,吴永健,等.血脂康对冠心病并发高脂血症患者纤溶功能的影响[J].中国煤炭工业医学杂志,2002,5(1):61-62
56.吴永健,俞虹,崔燕玲.不同类型高脂血症小而密低密度脂蛋白的水平及调血脂治疗对其影响[J].中国循环杂志,2002,17(6):431-433
57.Shui-Ping Zhao,Ling Liu,et al.Effect of xuezhikang,a cholestin extract,on reflecting postprandial triglyceridemia after a high-fat meal in patients with coronary heart disease[J].Atherosclerosis,2003,168:375-380
58.王蔚.血脂康对颈动脉斑块的影响[J].中国临床药学杂志,2002,11(5):263-265
59.吴济荫.血脂康降低高脂血症患者血清可溶性粘附分子含量的观察[J].兰州医学院学报,2003,26(4):10-12
60.王锋,朱川.血脂康对血脂异常患者C-反应蛋白的影响[J].广州医药,2003,33(5)5:32-33
61.Ling Liu,Shui-Ping Zhao,et al.Xuezhikang decreases serum lipoprotein(a) and C-reactive protein concentrations in patients with coronary heart diease[J].Clinical Chemistry,2003,49(8):1347-1352
62.蔡树霞,孙薇.血脂康对高脂血症患者血小板活性及纤溶活性的影响[J].山东医药,2003,43(28):6-8
63.吕春华.血脂康对2型糖尿病糖、脂代谢及血小板活化功能的影响[J].广西医学,2003,25(1):16-18
64.江劲波.血脂康对高脂血症患者血脂谱的作用和对血栓素A2与前列环素的影响[J].中华内科杂志,1999,38(8):517
65.王曦云,盛莉.洛伐他汀治疗冠心病高胆固醇血症对血管内皮功能微循环及胰岛素敏感性的影响[J].中国实用内科杂志,2003,23(11):660-662
66.赵志明,王毅.血脂康对正常胆固醇水平不稳定性心绞痛患者血管内皮依赖性舒张功能的影响[J].中国中西医结合杂志,1999,19(11):38-40
67.程训民,余宗梅.血脂康对高脂血症患者血管内皮功能的影响[J].中国动脉硬化杂志,2001,9(3):235-237
68.杨海波,唐元升.血脂康对高脂血症患者内皮功能及血中一氧化氮与内皮素水平的影响[J].中国中西医结合杂志,2003,23(1):13-15
69.魏炜,李仁立.血浆高甘油三酯对老年人血管内皮功能的损害及血脂康的修复作用[J].临床心血管病杂志,2002,18(7):336-337
70.吴永健,俞虹.血脂康对冠心病合并高脂血症患者血管内皮细胞的保护作用[J].中华老年心脑血管病杂志,2002,4(5):319-321
71.程艳春,赵水平.调脂治疗对冠心病患者餐后血管内皮功能的影响[J].中华心血管病杂志,2004, 32(2):114-117
72.陈建国,徐伯平.血脂康对老年陈旧性心肌梗塞患者氧化修饰低密度脂蛋白及血管内皮功能的影响[J].南京医科大学学报,2001,21(4):322-324
73.李国平,欧阳淼.血脂康降脂作用与血清一氧化氮关系的研究[J].临床心血管病杂志,2002,18(4):169-170
74.王曦云,盛莉.洛伐他汀治疗冠心病高胆固醇血症对血管内皮功能微循环及胰岛素敏感性的影响[J].中国实用内科杂志,2003,23(11):660-662
75.曾祥义,潘婕.血脂康对2型糖尿病合并高脂血症血管内皮细胞保护作用的临床观察[J].第三军医大学学报,2001,23(6):726-728
76.王景明,吕秀云.血脂康对高血压病患者左室功能及重构的影响[J].临床荟萃,2000,15(14):645-646
77.周宁,朱丽琼.血脂康对糖尿病甲皱微循环及血液流变学的影响[J].中华实用医学,2001,3(1):56-57
78.郑华,丹笑颖.血脂康改善血流变学及临床疗效观察[J].河北医学,2001,7(1):46-48
79.徐轶,魏群.血脂康胶囊治疗原发性高脂血症伴高粘血症50例疗效观察[J].河北中医,2000,22(7):525-526
80.张东翔,袁俊强,李玉杰.血脂康治疗高脂血症临床疗效观察[J].中华内科杂志,1998,37(6):4021
81.秦树存,张维强,赵美玲,等.随机双盲对照试验观察血脂康对老年高脂血症患者的临床功效[J].中华内科杂志,1998,37(6):4011
82.梁敬芝,伍春凤,姚盛思.血脂康治疗53例高脂血症临床分析[J].广西医学,2006,28(1):123
83.戴小华,卓秀珍.血脂康胶囊对不稳定性心绞痛患者血脂异常的影响[J].中药新药与临床药理,1999,10(4):68-69
84.邓洁,雷芸,彭春花.血脂康治疗急性心肌梗死伴高脂血症临床观察[J].首都医药,2000,7(1):42-43
85.王伟华,章辉喻,艳林葛,等.血脂康对不同血脂水平的急性冠状动脉综合征患者的干预作用[J].中国中西医结合杂志,2004,24(12):1073-1076
86.张戈,杨瑞丰,阮志敏,等.不同剂量血脂康调脂疗效的临床观察[J].中国实用内科杂志,2002,22(5):304-305
87.熊辉,胡琴,夏玲玲.不同剂量血脂康调脂疗效的研究[J].现代中西医结合杂志,2003,12(5):1577-1578
88.曾群英,麦炜颐,高修仁,等.2种剂量血脂康胶囊治疗高脂血症的临床研究[J].中国新药杂志,2002,11(3):229-232
89.Wang M,Shen JJ,Huang SE,et al.To compare the effects of different do Xuezhikang with prova statin on blood lipids and inflammatory factors in patients with acute coronary syndrome[J].Prey Treat Cardio Cereb Vasc Dis 2005,5(5):14-16
90.王文宏.血脂康和阿托伐他汀治疗高胆固醇血症的疗效比较[J].实用中医内科杂志,2006,20(3):305
91.LIU Zhi-gao,YU Xi-yong.Effects of Xuezhikang Capsule on Blood Lipids,Platelet Activation and Coagulation-Fibrinolysis Activity in Patients with Hyperlipidemia[J].C JIM,2004,10(4):257-262
92.王素如.血脂康与洛伐他汀治疗高脂血症的疗效比较[J].中国新药与临床杂志,2000,19(4):249-251.
93.张海,张言镇.血脂康和洛托伐他汀治疗原发性高脂血症对比研究[J].实用新医学,2002,(6):481-482.
94.席蓓莉.血脂康与辛伐他汀治疗老年原发性高脂血症疗效比较[J].上海第二医科大学学报,2002,22(3):285-286.
95.郑英,罗希芝,王树玲,等.血脂康与辛伐他汀临床疗效的对照研究[J].中国药学杂志,2001,36(10):715
96.孙瑞华.血脂康与辛伐他汀治疗高脂血症的比较[J].中国药学杂志,2001,36(10):715
97.陈凌,秦永文.血脂康胶囊治疗高胆固醇的临床效果[J].药学服务与研究,2002,2(1):39-40
98.李玉珊,雷华芝.血脂康治疗老年高脂血症41例临床观察[J].中国全科医学,2003,6(2):163
99.殷玲,张桂清,王淑芳.血脂康治疗高脂血症的临床观察[J].现代中西医结合杂志,2000,9(7):599-601
100.高雷山,廖勇.血脂康、来适可调节冠心病患者血脂疗效观察[J].现代中西医结合杂志,2003,12(23):25-28
101.申明月.血脂康和阿托伐他汀治疗高脂血症的疗效比较[J].中华医学实践杂志,2003,2(5):439-440
102.陆国平,霍淑钦,沈永初,等.血脂康和辛伐他汀对高胆固醇血症调脂作用的比较[J].中华内科杂志,1998,37(6):3711
103.金炜,杨红,张承,等.血脂康和美百乐镇对照治疗原发性高脂血症[J].中国新药杂志,1997,6(4):2651
104.金智敏,赵晓薇.血脂康与非诺贝特对高血压高危患者高脂血症的疗效对比研究[J].上海医药,2002,23(4):171-172
105.傅蓉蓉,李群血脂康治疗高脂血症[J].中国临床药学杂志,2000,9(4):243-244
106.王卫霞,陈可冀.血脂康胶囊治疗高脂血症有效性和安全性的系统评价[J].Chin J Evid-based Med,2006,Vol.6(5):352-358
107.王健,肖明英.血脂康联合小剂量阿司匹林治疗冠心病并高脂血症65例的长期疗效观察[J].新医学,2000,31(10):596-597
108.王爱娥,白根明.血脂康治疗冠心病心绞痛疗效观察[J].山西职工医学院学报,2003,13(1):23-24
109.陶钦洪,贾连旺.血脂康对老年冠心病患者血脂及血液流变学影响的观察[J].浙江临床医学,2005,7(12):1295-1296
110.薛连喜,藤雅轩.血脂康对冠心病并发高脂血症病人血管内皮功能及C反应蛋白的影响[J].中西医结合心脑血管病杂志,2006,4(6:477-478
111.XU Zhi-min.Effects of Xuezhikang Cap sule on High Risk Population in Chinese Coronary Secondary Prevention Study(CCSPS) and the Enlightenment from It[J].Chin J Integr Med,2006,12(2):87-89
112.方咏红,李卫.血脂康对2型糖尿病患者脂代谢及胰岛B细胞功能影响的研究[J].首都医药,2000, 7(2):44
113.王彩玲,李曙远,张伟.血脂康对2型糖尿病人胰岛素敏感性的影响[J].中国糖尿病杂志,2001,9(3):171-173
114.戴小华,薛晓阳,汪玲,等.血脂康对高血压病合并血脂异常胰岛素敏感性的影响[J].中国中西医结合杂志,2000年,20(9):692-693
115.王景明,崔群,吕秀云,等.血脂康治疗胰岛素抵抗的疗效观察[J].潍坊医学院学报,2002,24(1):50-51
116.林永丽,左晶,王虹,等.血脂康治疗2型糖尿病合并高脂血症80例临床观察[J].中国老年医学杂志,2000,20(4):243-244
117.周黎,邬玲.血脂康治疗糖尿病合并血脂异常的疗效观察[J].ACMP,2002,30(5):40
118.彭卫华,曲强,陈健.血脂康对合并高脂血症的非胰岛素依赖型糖尿病患者微量白蛋白尿的影响[J].中国中西医结合肾病杂志,2001,(21):46-47
119.姚颖,刘晓城.血脂康治疗肾病综合征30例疗效观察[J].中国全科医学,2002,5(3):244-245
120.王学彬,刘玉夏.血脂康治疗慢性肾功能衰竭腹膜透析病人高脂血症[J].滨州医学院学报,2003,26(6):430-431
121.香瑶英,霍丽娟.血脂康治疗脂肪肝临床疗效观察[J].中国肝脏病杂志,200l,9(增刊):92-93
122.刘娅,赵经川,刘虹.血脂康治疗276例脂肪肝B超声像图变化[J].中华内科杂志,1999,38(8):554-555
123.陈丽娟,徐薇.联合血脂康治疗脂肪肝的临床观察[J].中华临床医药,2003,4(10):24-25
124.毕迅.血脂康治疗脑梗塞伴高脂血症疗效观察[J].首都医药,2000,7(4):35
125.孙惠华.血脂康对高脂血症患者颈动脉内2中膜厚度的影响[J].中国基层医药,2006,13(2):339
126.田沈,王溪原,窦文波,等.血脂康治疗60例高脂血症并颈动脉斑块临床观察[J].临床内科杂志,2005,22(10):713
127.郝兵.血脂康治疗颈动脉粥样硬化疗效观察[J].辽宁中医杂志,2006,33(5):558
128.Kannel WB,Castelli WP,Gordon T.Cholesterol in the prediction of atherosclerotic disease.New perspectives based on the Framingham study.Ann Intern Med.1979,90:85-91
129.Hunninghake D,LaRosa JC,Bush D,et al.The cholesterol facts.A joint statement by the American Heart Association and the National Heart,Lung,and Blood institute[J].American Heart Association Circulation,1990,81:1721-1733
130.Wakugami K,Iseki K,Kimura Y,et al.Relationship between serum cholesterol and the risk of acute myocardial infarction in a screened cohort in Okinawa[J],Japan Jpn Circ J,1998,62:7-14
131.Chen Z,Peto R,Collins R,et al.Serum cholesterol concentration and coronary heart disease in population with low cholesterol concentration[J].BMJ,1991,3(3):267-282
132.Pearson TA,Laurora I,Chu H,et al.The lipid treatment assessment project(L-TAP):a-multicenter survey to evaluate the percentages of dyslipidemic patients receiving lipid-lowing therapy and achieving lowdensity lipoprotein cholesterol goals[J].Arch Intern Med,2000,160:459-467
133.Freuhauf S,Veldwijk MR,Kramer A,et al.Baseline serum cholesterol and treatment effect in the Scandinavian Simvastatin Survial Sutdy(4S)[J].Lancet,1995,345(89):1274-1275
134.Sacks FM,Pfeffer MA,Moye LA,et al.The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels[J].New England Med.1996,335:1001-1009
135.Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels.The Long-Term Intervention with Pravastatin in Ischaemic Disease(LIPID) Study Group[J].New England Med,1998,339:1349-1357
136.West of Scotland Coronary Prevention Study:implication for clinical practice.The WOSCOPS Study Group[J].Europe Heart 1996,17:163-164
137.Downs JR,Clearfield M,Weis S,et al.Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels:results of AFCAPS/TexCAPS.Air Force/Texas Coronary Atherosclerosis Prevention Study[J].JAMA,1998,279:1615-1622
138.杨宝峰,苏定冯.药理学[S].第六版.北京:人民卫生出版社,2003:282-283
139.Goldman,Bennett.Cecil Textbook of Medicine,21th edition.[M].北京:世界图书社,2003:16-17
140.Lea AP,Mc Tavish D.Atorvastatin,a review of its pharmacology and therapeutic potential in the management of hyperlipidaemias[J].Drugs,1997,53:828-847
141.Dean G.Compafison of efficacy and safety of atorvastatin and simvastatin in patients with dyslipidemia with and without coronary disease[J].Am J Cardio,2002,89:667-671
142.Dresser GK,Spence JD,Bailey DG,et al.Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition[J].Clin Pharmacolinet,2000,38(1):41
143.Foley KA,Massing MW,Simpson RJ,et al.The cholesterol ester transfer protein TaqlB gene polymorphism predicts clinical benefit of statin therapy in patients with significant coronary artery disease[J].Am Heart J 2003,146:1007-1014
144.陆纪宏.试论中医辨治高脂血症[J].辽宁中医杂志,1991,2:2
145.简亚平.高脂血症中医药研究近况述评[J].湖南中医学院学报,1999,19(1):62
146.吴松鹰,林求诚,杨持.老年脂质代谢紊乱中医医患因素临床调查[J].中国中西医结合杂志,1993,13(5):273
147.张继东,高洪春,李长华主编.心血管病当代中医治疗[M].第一版.济南:济南出版社,1996:115
148.宋剑南,刘东远,牛晓红,等.高脂血症与中医痰浊关系的实验研究[J].中国中医基础医学杂志,1995,1(1):49
149.俞亚琴,郭兮华.从血液流变学探讨高脂血症的痰湿改变[J].辽宁中医杂志,1995,22(6):241