降脂红曲微粉对高脂血症临床疗效的对比研究
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摘要
目的：观察不同剂量降脂红曲微粉对高脂血症的临床疗效和安全性，为降脂红曲的临床应用和开发提供科学依据。方法：80例高脂血症患者随机分为4个组，A组(降脂红曲微粉1／2剂量组)，B组(降脂红曲微粉组)，C组(降脂红曲粗粉组)和D组(血脂康组)。观察治疗前后临床症状、血脂与抗氧化、血管内皮分泌功能及肱动脉内皮依赖性舒张功能等指标变化。结果：4组用药50天后，临床症状均明显改善，A、B两组临床症状总疗效的显效率及乏力症状改善的总有效率明显优于C、D两组。各组血清总胆固醇非常显著降低，其他实验室指标亦有不同程度的改善；A、D两组降脂总有效率显著优于C组；A组甘油三酯含量显著降低，降钙素基因相关肽显著升高；A、D两组肱动脉内皮依赖性舒张功能显著改善，内皮素／降钙素基因相关肽显著降低，后4项指标其他组未见显著改变。结论：降脂红曲微粉降脂与缓解临床症状疗效肯定，安全有效，且具有抗氧化，保护血管内皮等作用，剂量可以较常规粉碎者减半，值得推广应用。
Objective: To observe the therapeutic effect and security on treatment of
hyperlipemia with different doses of micro-powder of lipid-reducing Hongqu(MLH),
and provide scientific proof for its clinical application and development. Methods:
80 cases of hyperlipemia patients were divided randomly into 4 groups: 21 cases in
Group A (MLH of 1/2 dose group), 20 cases in Group B(MLH of full dose group),19 cases in
Group C(rough-powder of lipid-reducing Hongqu group) and 20 cases in group D(Xuezhikang group).
To observe the changes of clinical symptoms, blood lipid , anti-oxidation, secretion function
of vascular endothelium and endothelium-dependent relaxing function of brachial artery. Results: After 50 days of treatment,
clinical symptoms improved in all groups, and the significant effective rate and total effective
rate to tiredness of A and B groups were superior to those of C and D groups. TC in all groups reduced remarkably, and other
laboratory indexes improved with different extent in each group. Total effective rate of A and B groups in reducing
lipid was superior to that of C group. TG reduced and CGRP elevated in group A. Endothelium-dependent diastolic
function of brachial artery improved and ET/CGRP reduced in A and D groups. Conclusion: MLH had such merits:
confirmative lipid-reducing effect, relieving clinical symptoms remarkably and safely,
anti-oxidation and protecting vascular endothelium. Its dose was half of the normal, and, deserved to be spread and
applied.
Objective: To observe the therapeutic effect and security on treatment of
hyperlipemia with different doses of micro-powder of lipid-reducing Hongqu(MLH),
and provide scientific proof for its clinical application and development. Methods:
80 cases of hyperlipemia patients were divided randomly into 4 groups: 21 cases in
Group A (MLH of 1/2 dose group), 20 cases in Group B(MLH of full dose group),19 cases in
Group C(rough-powder of lipid-reducing Hongqu group) and 20 cases in group D(Xuezhikang group).
To observe the changes of clinical symptoms, blood lipid , anti-oxidation, secretion function
of vascular endothelium and endothelium-dependent relaxing function of brachial artery. Results: After 50 days of treatment,
clinical symptoms improved in all groups, and the significant effective rate and total effective
rate to tiredness of A and B groups were superior to those of C and D groups. TC in all groups reduced remarkably, and other
laboratory indexes improved with different extent in each group. Total effective rate of A and B groups in reducing
lipid was superior to that of C group. TG reduced and CGRP elevated in group A. Endothelium-dependent diastolic
function of brachial artery improved and ET/CGRP reduced in A and D groups. Conclusion: MLH had such merits:
confirmative lipid-reducing effect, relieving clinical symptoms remarkably and safely,
anti-oxidation and protecting vascular endothelium. Its dose was half of the normal, and, deserved to be spread and
applied.
引文
[1] 王利谚，李红宝，车胜荣．HMG-CoA还原酶抑制剂新进展及其临床应用．华西药学杂志，1996；11(3)：168．
[2] 何煜，郭琪，杜晓敏。中药细胞级微粉碎对体内吸收的影响．中成药，1999；21(11)：601～602．
[3] 李春华，林强，裴重华，等．中药三七的超细粉碎工艺与产品物性研究．中国粉体技术，2001；7(6)：21～22．
[4] 杨新林，朱鹤孙，赵东旭．灵芝破壁孢子与不破壁孢子的显微镜观察与生化测定比较研究．中草药，1997；28(12)：721～723．
[5] 中华心血管病杂志编辑委员会血脂异常防治对策专题组．血脂异常防治建议．中华心血管病杂志，1997；25(3)：169～172．
[6] Celermajer DS,Sorensen KE,Gooch VM,et al.Non-invasive Detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet, 1992; 340:1111～1115.
[7] 中药新药临床研究指导原则．国家药品监督管理局，2002．
[8] 包启安．红曲的渊源及其培养技术的发展．中国酿造，2002；(1)：5～7．
[9] Endo.A, Monacolin. K.A new hypocholesterolemic agent produced by a Monascus species. The Journal Of Antibiotics, 1979;32:852～854.
[10] Endo. A, Hasuimi. K, Neishi.S. Monacolin J and L, new inhibitors of cholesterol biosynthesis produced by Monascusrumber. The Journal Of Antibiotics, 1985;38(3): 420～422
[11] Endo.A, Hasuimi. K, Nakmura. T, et al. Dihydromonacolin L and Monacolin Ⅹ, new metabolities those inhibit cholesterol biosynthesis. The Journal Of Antibiotics, 1985;38(3):321～327.
[12] Moor. R, Bigam.G, Chan.J, et al. Studies on the glucoamylase from Monascus rubiginosus. J. Am. Chem. Sci,1985;107(12):3694～3701.
[13] Komagata. D, Shimada. H, Murakawa.s, Endo.A. Biosynthesis of Monacolin L to Monacolin J by a Monooxygenase of Momagata rubber. The Journal Of Antibiotics,
1989;(42):407-412.
[14] Endo.A,Komagata.D,Shimada.H.Monacolins M,a new inhibitor of cholesterol biosysthesis.The Journal of Antibiotics,1986;(39):1670～1677.
[15] 王银叶，韦薇，李长龄．特种红曲对鹌鹑实验性脂肪肝的治疗作用．中国临床药理学 与治疗学，2002；7(4)：293～295．
[16] 宫慧梅，阿布力米提·克里木，赵树新．红曲安全性研究进展．广州食品工业科技， 2002；18(1)：60～62．
[17] 骆苏芳，翁甲丰，冼显秀，等．浅谈超微细中药粉体．中药材，1999；22(4)：209～211．
[18] 王爱武，吕文海，耿晖．超微粉碎在中药生产中应用概况及展望．时珍国医国药，2000；11(7)：669～670．
[19] 陆付耳，阮金兰，余达经，等．试论微米中药．世界科学技术-中药现代化，2001；3(1)：12～15．
[20] 李春华，林强，裴重华，等．中药三七的超细粉碎工艺与产品物性研究．中国粉体技术，2001；7(6)：21～22．
[21] 黄芳，郭立玮，金万勤．药物累积法测定普通马钱子粉与超细马钱子粉的表观药动学参数．南京中医药大学学报(自然科学版)，2001；17(3)：162～163．
[22] 黄芳，郭立玮袁红宇，等．超细粉体技术对二妙丸体内吸收、分布的影响．南京中医药大学学报(自然科学版) ，2002；18(4)：216～218．
[23] 吕文海，邱福军，王作明．炮制与超微粉碎对水蛭药效影响的初步实验研究．中国中药杂志，2001；26(4)：241～244．
[24] 刘莉，徐新刚，高鹏，等．川芎不同入药形式的体外溶出与药效学比较．中成药，2002；24(4)：246～248．
[25] 薛焰，郭立玮，袁红宇，等．药理效应法测定超细粉马钱子和普通粉马钱子的药动学参数．南京中医药大学学报(自然科学版)，2002；18(2)：94～95
[26] 孙冰，徐劲，涂群．菊乐牌舒胸片微粉技术研究及其临床应用．引进国外医药技术与设备，1999；5(10)：53～54．
[27] 张文高，王显刚，谢庆成，等．益气活血法与益气活血解毒法治疗不稳定性心绞痛及其作用机制研究．第三次全国中西医结合养生学与康复医学学术研讨会论文集，2002；63～70．
[28] 楼定安．应用显微荧光光度术研究血管壁通透性．中华心血管病杂志，1983；11：134．
[29] ShimamotoT. Contraction of endothelial cells as a key mechanism inatherosclerosis and treatment of atherosclerosis with endothelial cell relectantin;Atherosclerosis Ⅲ. Eds Schettler G and Weizl A, New York, Springer Verlag,1974;64～80.
[30] 冯宁，冯宗忱．小、密低密度脂蛋白与冠心病．中华心血管病杂志，1997；25(3)：237．
[31] 赵水平，王钟林，陆宗良．临床血脂学，湖北：湖南科技出版社，1997；第1版：72．
[32] 高俊，刘德培．载脂蛋白 ApoA Ⅰ抗动脉粥样硬化的相关研究．北京大学学、报，2001；33(4)：320～321．
[33] Fless GM, Zum Mallen ME, Scanu AM.Isolation of apolipoprotein(a) from lipoprotein(a).J Lipid Res, 1985;26(1):224～229.
[34] Palela J Schreiner. Lipoprotein(a) as a risk factor for preclinical atherosclerosis. Atherosclerosis Thrombosis, 1993;13(6):826.
[35] Klezovitch O, Edelsteon C, Ling Yang Zhu, et al. J Biol Chem, 1998; 273(37): 23856～23865.
[36] 李江，赵水平．血管内皮依赖性舒张功能失调的检测和临床意义．国外医学生理、病理科学与临床分册，1997；17(2)：154～156．
[37] 马学盛，张文高，周苏宁．一氧化氮与中医药防治心血管疾病．第二届全国中西医结合养生和康复医学学术交流会论文集，1998：68．
[38] Dymshitz J, Vasko MR.Endothelin-1 enhances capsaicin-induced peptide release and cGMP accumulation in cultures of rat sensory neurons. Neurosci Lett, 1994;167(1-2):128～132.
[39] Tanner FC. Endothelium-derived nitric oxide, endothelin and platelet vessel wall interaction: Alterations in hypercholesterolemia and athero-sclerosis. Seminars in Thromb Hernost, 1995; 18:167.
[40] 李江，赵水平，张湘瑜，等．新伐他汀降脂治疗对血管内皮依赖性舒张功能的影响．中华心血管病杂志，1998；26(4)：278～281．
[41] Egashira K,Inou T, Hirooca Y, et al.Impaired coronary blood flow response to acetylcholine in patients with coronary risk factors and proximal atherosclerotie lesions.J Clin Invest, 1993;91(1):29～37.
[42] 李向平，赵水平，张湘瑜，等．高密度脂蛋白对血管内皮依赖性舒张功能的影响．中华心血管病杂志，2000；28(3)：203～206．
[43] 程训民，余宗梅，骆合德，等．血脂康对高脂血症患者血管内皮功能的影响．中国动脉硬化杂志，2001；9(3)：235～237．
[44] 赵玉霞，刘运芳，张梅．祛瘀消斑胶囊对血脂及血管内皮依赖性舒张功能的影响．南京中医药大学学报(自然科学版)，2002；18(2)：89～91．
[45] Ohara Y. The action of oxygen-centrad free radical on human. Circulation, 1996; 95:898～903.
[46] 钟慈声，孙安阳．一氧化氮的生物医学，上海：上海医科大学出版社，1997，第1版：102．
[47] Stubbs CD & Smith AD. The modification of mammalian membrane poly-unsaturated fatty acid composition in relation to membrane fluidity and function. Biochem Biophy Acta 1984; 779:89～137.
[48] Henriksen T. Enhanced macrophage degradation of biologically modified low density lipoprotein. Arteriosclerosis, 1983; 3:149.
[49] Koiani K. Kondo A. Blanabe Ⅺ. Et al. Determination of melondialdehyde-modified LDL(MDA-LDL) and its potential usefulness. Rinsho Byori, 1997;45:47.
[50] Moncada S, Palmer RMJ, Higgs EA. Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol Rey, 1991;43:109～142.
[51] Lefer AM, Ma XL,. Decreased basal nitric oxide release in hyperchole-sterolemia increases neutrophil adherence to rabbit coronary artery endothelium. Arterioscler Thromb, 1993;13: 771～776.
[52] Watt GF. Mandalia, S Brunt JNH. Et al. Independent association between plasma lipoprotein subfraction level and the course of coronary artery disease in the St Thomas Atherosclerosis Regression Study. Metabolism, 1993;42:1461.
[53] Rice-Evens C and Bruckdorfer KR. Free radicals, lipoproteins and cardiovascular dysfunction. Pergamon Press, Oxford, 1992;42～60.
[54] 李芹，荆清．一氧化氮和氧化低密度脂蛋白相互作用及其与动脉粥样硬化的关系．国外医学心血管疾病分册，1996；26(1)：10～13．
[55] Holmes RP.The effect of membrane lipid composition on the permeability of
membranes to Ca. In Annals New York Academy Sciences, 1983; 44～56.
[56] Lim. Biochemical, structure and functional propreties of oxidized low density lipoprotein. J Clin Invest, 1996;94:122～133.
[2] 何煜，郭琪，杜晓敏。中药细胞级微粉碎对体内吸收的影响．中成药，1999；21(11)：601～602．
[3] 李春华，林强，裴重华，等．中药三七的超细粉碎工艺与产品物性研究．中国粉体技术，2001；7(6)：21～22．
[4] 杨新林，朱鹤孙，赵东旭．灵芝破壁孢子与不破壁孢子的显微镜观察与生化测定比较研究．中草药，1997；28(12)：721～723．
[5] 中华心血管病杂志编辑委员会血脂异常防治对策专题组．血脂异常防治建议．中华心血管病杂志，1997；25(3)：169～172．
[6] Celermajer DS,Sorensen KE,Gooch VM,et al.Non-invasive Detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet, 1992; 340:1111～1115.
[7] 中药新药临床研究指导原则．国家药品监督管理局，2002．
[8] 包启安．红曲的渊源及其培养技术的发展．中国酿造，2002；(1)：5～7．
[9] Endo.A, Monacolin. K.A new hypocholesterolemic agent produced by a Monascus species. The Journal Of Antibiotics, 1979;32:852～854.
[10] Endo. A, Hasuimi. K, Neishi.S. Monacolin J and L, new inhibitors of cholesterol biosynthesis produced by Monascusrumber. The Journal Of Antibiotics, 1985;38(3): 420～422
[11] Endo.A, Hasuimi. K, Nakmura. T, et al. Dihydromonacolin L and Monacolin Ⅹ, new metabolities those inhibit cholesterol biosynthesis. The Journal Of Antibiotics, 1985;38(3):321～327.
[12] Moor. R, Bigam.G, Chan.J, et al. Studies on the glucoamylase from Monascus rubiginosus. J. Am. Chem. Sci,1985;107(12):3694～3701.
[13] Komagata. D, Shimada. H, Murakawa.s, Endo.A. Biosynthesis of Monacolin L to Monacolin J by a Monooxygenase of Momagata rubber. The Journal Of Antibiotics,
1989;(42):407-412.
[14] Endo.A,Komagata.D,Shimada.H.Monacolins M,a new inhibitor of cholesterol biosysthesis.The Journal of Antibiotics,1986;(39):1670～1677.
[15] 王银叶，韦薇，李长龄．特种红曲对鹌鹑实验性脂肪肝的治疗作用．中国临床药理学 与治疗学，2002；7(4)：293～295．
[16] 宫慧梅，阿布力米提·克里木，赵树新．红曲安全性研究进展．广州食品工业科技， 2002；18(1)：60～62．
[17] 骆苏芳，翁甲丰，冼显秀，等．浅谈超微细中药粉体．中药材，1999；22(4)：209～211．
[18] 王爱武，吕文海，耿晖．超微粉碎在中药生产中应用概况及展望．时珍国医国药，2000；11(7)：669～670．
[19] 陆付耳，阮金兰，余达经，等．试论微米中药．世界科学技术-中药现代化，2001；3(1)：12～15．
[20] 李春华，林强，裴重华，等．中药三七的超细粉碎工艺与产品物性研究．中国粉体技术，2001；7(6)：21～22．
[21] 黄芳，郭立玮，金万勤．药物累积法测定普通马钱子粉与超细马钱子粉的表观药动学参数．南京中医药大学学报(自然科学版)，2001；17(3)：162～163．
[22] 黄芳，郭立玮袁红宇，等．超细粉体技术对二妙丸体内吸收、分布的影响．南京中医药大学学报(自然科学版) ，2002；18(4)：216～218．
[23] 吕文海，邱福军，王作明．炮制与超微粉碎对水蛭药效影响的初步实验研究．中国中药杂志，2001；26(4)：241～244．
[24] 刘莉，徐新刚，高鹏，等．川芎不同入药形式的体外溶出与药效学比较．中成药，2002；24(4)：246～248．
[25] 薛焰，郭立玮，袁红宇，等．药理效应法测定超细粉马钱子和普通粉马钱子的药动学参数．南京中医药大学学报(自然科学版)，2002；18(2)：94～95
[26] 孙冰，徐劲，涂群．菊乐牌舒胸片微粉技术研究及其临床应用．引进国外医药技术与设备，1999；5(10)：53～54．
[27] 张文高，王显刚，谢庆成，等．益气活血法与益气活血解毒法治疗不稳定性心绞痛及其作用机制研究．第三次全国中西医结合养生学与康复医学学术研讨会论文集，2002；63～70．
[28] 楼定安．应用显微荧光光度术研究血管壁通透性．中华心血管病杂志，1983；11：134．
[29] ShimamotoT. Contraction of endothelial cells as a key mechanism inatherosclerosis and treatment of atherosclerosis with endothelial cell relectantin;Atherosclerosis Ⅲ. Eds Schettler G and Weizl A, New York, Springer Verlag,1974;64～80.
[30] 冯宁，冯宗忱．小、密低密度脂蛋白与冠心病．中华心血管病杂志，1997；25(3)：237．
[31] 赵水平，王钟林，陆宗良．临床血脂学，湖北：湖南科技出版社，1997；第1版：72．
[32] 高俊，刘德培．载脂蛋白 ApoA Ⅰ抗动脉粥样硬化的相关研究．北京大学学、报，2001；33(4)：320～321．
[33] Fless GM, Zum Mallen ME, Scanu AM.Isolation of apolipoprotein(a) from lipoprotein(a).J Lipid Res, 1985;26(1):224～229.
[34] Palela J Schreiner. Lipoprotein(a) as a risk factor for preclinical atherosclerosis. Atherosclerosis Thrombosis, 1993;13(6):826.
[35] Klezovitch O, Edelsteon C, Ling Yang Zhu, et al. J Biol Chem, 1998; 273(37): 23856～23865.
[36] 李江，赵水平．血管内皮依赖性舒张功能失调的检测和临床意义．国外医学生理、病理科学与临床分册，1997；17(2)：154～156．
[37] 马学盛，张文高，周苏宁．一氧化氮与中医药防治心血管疾病．第二届全国中西医结合养生和康复医学学术交流会论文集，1998：68．
[38] Dymshitz J, Vasko MR.Endothelin-1 enhances capsaicin-induced peptide release and cGMP accumulation in cultures of rat sensory neurons. Neurosci Lett, 1994;167(1-2):128～132.
[39] Tanner FC. Endothelium-derived nitric oxide, endothelin and platelet vessel wall interaction: Alterations in hypercholesterolemia and athero-sclerosis. Seminars in Thromb Hernost, 1995; 18:167.
[40] 李江，赵水平，张湘瑜，等．新伐他汀降脂治疗对血管内皮依赖性舒张功能的影响．中华心血管病杂志，1998；26(4)：278～281．
[41] Egashira K,Inou T, Hirooca Y, et al.Impaired coronary blood flow response to acetylcholine in patients with coronary risk factors and proximal atherosclerotie lesions.J Clin Invest, 1993;91(1):29～37.
[42] 李向平，赵水平，张湘瑜，等．高密度脂蛋白对血管内皮依赖性舒张功能的影响．中华心血管病杂志，2000；28(3)：203～206．
[43] 程训民，余宗梅，骆合德，等．血脂康对高脂血症患者血管内皮功能的影响．中国动脉硬化杂志，2001；9(3)：235～237．
[44] 赵玉霞，刘运芳，张梅．祛瘀消斑胶囊对血脂及血管内皮依赖性舒张功能的影响．南京中医药大学学报(自然科学版)，2002；18(2)：89～91．
[45] Ohara Y. The action of oxygen-centrad free radical on human. Circulation, 1996; 95:898～903.
[46] 钟慈声，孙安阳．一氧化氮的生物医学，上海：上海医科大学出版社，1997，第1版：102．
[47] Stubbs CD & Smith AD. The modification of mammalian membrane poly-unsaturated fatty acid composition in relation to membrane fluidity and function. Biochem Biophy Acta 1984; 779:89～137.
[48] Henriksen T. Enhanced macrophage degradation of biologically modified low density lipoprotein. Arteriosclerosis, 1983; 3:149.
[49] Koiani K. Kondo A. Blanabe Ⅺ. Et al. Determination of melondialdehyde-modified LDL(MDA-LDL) and its potential usefulness. Rinsho Byori, 1997;45:47.
[50] Moncada S, Palmer RMJ, Higgs EA. Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol Rey, 1991;43:109～142.
[51] Lefer AM, Ma XL,. Decreased basal nitric oxide release in hyperchole-sterolemia increases neutrophil adherence to rabbit coronary artery endothelium. Arterioscler Thromb, 1993;13: 771～776.
[52] Watt GF. Mandalia, S Brunt JNH. Et al. Independent association between plasma lipoprotein subfraction level and the course of coronary artery disease in the St Thomas Atherosclerosis Regression Study. Metabolism, 1993;42:1461.
[53] Rice-Evens C and Bruckdorfer KR. Free radicals, lipoproteins and cardiovascular dysfunction. Pergamon Press, Oxford, 1992;42～60.
[54] 李芹，荆清．一氧化氮和氧化低密度脂蛋白相互作用及其与动脉粥样硬化的关系．国外医学心血管疾病分册，1996；26(1)：10～13．
[55] Holmes RP.The effect of membrane lipid composition on the permeability of
membranes to Ca. In Annals New York Academy Sciences, 1983; 44～56.
[56] Lim. Biochemical, structure and functional propreties of oxidized low density lipoprotein. J Clin Invest, 1996;94:122～133.