温胆汤降脂作用研究
|
摘要
运用药理及生理学方法，通过腹腔注射蛋黄乳剂的方法建立急性高脂血症小鼠模型，观察温胆汤对急性高脂血症成年小鼠体重增长、粪便脂质含量、血清总胆固醇(TC)、血清总甘油三酯(TG)、低密度胆固醇(LDL-c)、血清丙二醛(MDA)含量、血清超氧化物歧化酶(SOD)活性、肝脏总脂解酶(LA)活性、脂蛋白脂肪酶(LPL)活性和肝脂酶(HL)活性的影响，并与西药吉非罗齐进行比较。结果表明温胆汤可有效控制小鼠体重增长，降低粪便脂质含量，显著降低急性高脂血症小鼠血清TC、TG、LDL-c含量(P＜0.05)，且疗效优于吉非罗齐。温胆汤还可提高血清SOD活性，降低MDA含量，降低体内脂质过氧化程度。同时，温胆汤可提高肝脏脂蛋白脂肪酶LPL和肝脏总脂解酶(LA)活性，但对肝脂酶(HL)活性无明显影响。
运用脂肪乳灌胃的方法建立慢性高脂血症小鼠模型，观察温胆汤对慢性高脂血症小鼠血清TC、TG以及高密度胆固醇(LDL-c)含量的影响。结果表明，温胆汤可有效降低慢性高脂血症小鼠血清TC、TG含量，疗效优于吉非罗齐，但对HDL-c含量的升高无明显效果。
在建立大鼠高脂血症模型基础上，观察温胆汤对大鼠血脂(TC、TG)水平、总脂解酶(LA)、脂蛋白脂酶(LPL)和肝脂酶(HL)活性、部分血象指标以及肝脏低密度脂蛋白受体(LDLR)基因表达的影响。结果表明温胆汤能够显著抑制高脂血症大鼠血清总胆固醇(TC)、血清总甘油三酯(TG)浓度，提高脂蛋白脂酶(LPL)和总脂解酶(LA)活性，但对肝脂酶(HL)活性无明显影响；血象部分指标，如：红细胞计数(RBC)、血红蛋白浓度(HGB)、
血球压积时IC＊）、血小板计数（班C）、血小板分分宽度o＊w）、血小板
平均体积（MPV）等显示说测！汤能降低血液粘度，有一定的抗血液凝集作用；逆
转录聚合酶链反应（RTPCR）实验显示高脂饲料能显著降低大鼠肝脏LDLR
m删A水平，温胆汤能显著升高大鼠肝脏LDLR mRNA水平。山此jjJ见，温胆
汤可能主要通过调节大鼠肝脏LDLR转录水平顶防脂质代谢紊乱。
We studied the influence of WenDan Decoction on the disorder of lipid metabolism in experimental mice of acute hyperlipemia model. To prove the regulating action of WenDan Decoction for serum fat of adult mice, we studied Triglycerides(TG), Total Cholesterol (TC)> LDL-c, SOD, MDA in serum, and LA, LPL, HL in liver and fat content in faeces of adult mice, compared with Western medicine (Gemfibrozil) at the same time. Results suggest that wenDantang can markerly decrease TG, TC, LDL-c, MDA in serum of acute hyperlipermia model mice and increase the action of SOD, LPL and LA, but don't act on HL. The results also suggest that the impact of WenDan Decoction group was better than other groups(p<0.05).
In the model of chronic hyperlipermia mice, We studied Triglycerides(TG), Total Cholesterol (TC) and HDL-c in serum, the result suggest that WenDan Decoction can decrease TG, TC in serum of chronic hyperlipermia model mice, but it can't influence HDL-c.
On the basis of establishing hyperlipidemia rat model, Triglycerides(TG), Total Cholesterol (TC) in serum, activities of Lipase (LA), Lipoprotein Lipase (LPL), Hepatic Lipase (HL) in liver, parts of hemogram and hepatic LDLR mRNA levels were investigated after 21 days feeding of atherogenic diet. The results suggest that WenDan Decoction significantly reduced the serum TG,TC and increase the activity of LPL and LA, but nullity in HL. At the same time parts of hemogram index such as Red Blood Cell Count (RBC), Assay of Hemoglobin (HGB), Assay of Hematocrit
in Blood (HCT), Blood Platelet Count (BPC)> Platelet Distribution Width (PDW) and Mean Platelet Volume (MPV) suggest that WenDantang can lessen blood viscosity and have anticlotting effect. The result of RT-PCR test showed that high fat and high cholesterol feeding can significantly induce the reduction of LDLR mRNA levels, while WenDan Decoction can increase hepatic LDLR density. In sum, WenDan Decoction can prevent disorder of lipid Metabolism by regulating TC, TG, LDL-c through upregaulation of LDLR transcription level and improving ability of antioxidant.
运用脂肪乳灌胃的方法建立慢性高脂血症小鼠模型，观察温胆汤对慢性高脂血症小鼠血清TC、TG以及高密度胆固醇(LDL-c)含量的影响。结果表明，温胆汤可有效降低慢性高脂血症小鼠血清TC、TG含量，疗效优于吉非罗齐，但对HDL-c含量的升高无明显效果。
在建立大鼠高脂血症模型基础上，观察温胆汤对大鼠血脂(TC、TG)水平、总脂解酶(LA)、脂蛋白脂酶(LPL)和肝脂酶(HL)活性、部分血象指标以及肝脏低密度脂蛋白受体(LDLR)基因表达的影响。结果表明温胆汤能够显著抑制高脂血症大鼠血清总胆固醇(TC)、血清总甘油三酯(TG)浓度，提高脂蛋白脂酶(LPL)和总脂解酶(LA)活性，但对肝脂酶(HL)活性无明显影响；血象部分指标，如：红细胞计数(RBC)、血红蛋白浓度(HGB)、
血球压积时IC＊）、血小板计数（班C）、血小板分分宽度o＊w）、血小板
平均体积（MPV）等显示说测！汤能降低血液粘度，有一定的抗血液凝集作用；逆
转录聚合酶链反应（RTPCR）实验显示高脂饲料能显著降低大鼠肝脏LDLR
m删A水平，温胆汤能显著升高大鼠肝脏LDLR mRNA水平。山此jjJ见，温胆
汤可能主要通过调节大鼠肝脏LDLR转录水平顶防脂质代谢紊乱。
We studied the influence of WenDan Decoction on the disorder of lipid metabolism in experimental mice of acute hyperlipemia model. To prove the regulating action of WenDan Decoction for serum fat of adult mice, we studied Triglycerides(TG), Total Cholesterol (TC)> LDL-c, SOD, MDA in serum, and LA, LPL, HL in liver and fat content in faeces of adult mice, compared with Western medicine (Gemfibrozil) at the same time. Results suggest that wenDantang can markerly decrease TG, TC, LDL-c, MDA in serum of acute hyperlipermia model mice and increase the action of SOD, LPL and LA, but don't act on HL. The results also suggest that the impact of WenDan Decoction group was better than other groups(p<0.05).
In the model of chronic hyperlipermia mice, We studied Triglycerides(TG), Total Cholesterol (TC) and HDL-c in serum, the result suggest that WenDan Decoction can decrease TG, TC in serum of chronic hyperlipermia model mice, but it can't influence HDL-c.
On the basis of establishing hyperlipidemia rat model, Triglycerides(TG), Total Cholesterol (TC) in serum, activities of Lipase (LA), Lipoprotein Lipase (LPL), Hepatic Lipase (HL) in liver, parts of hemogram and hepatic LDLR mRNA levels were investigated after 21 days feeding of atherogenic diet. The results suggest that WenDan Decoction significantly reduced the serum TG,TC and increase the activity of LPL and LA, but nullity in HL. At the same time parts of hemogram index such as Red Blood Cell Count (RBC), Assay of Hemoglobin (HGB), Assay of Hematocrit
in Blood (HCT), Blood Platelet Count (BPC)> Platelet Distribution Width (PDW) and Mean Platelet Volume (MPV) suggest that WenDantang can lessen blood viscosity and have anticlotting effect. The result of RT-PCR test showed that high fat and high cholesterol feeding can significantly induce the reduction of LDLR mRNA levels, while WenDan Decoction can increase hepatic LDLR density. In sum, WenDan Decoction can prevent disorder of lipid Metabolism by regulating TC, TG, LDL-c through upregaulation of LDLR transcription level and improving ability of antioxidant.
引文
1．于晓光，王继芬等．高脂血症沙鼠组织中某些酯酶活性的变化及药物降脂作用的研究．哈尔滨医科大学学报，1997；31(1)：12～14
2．蒋宪成，庄庆祺，梅美珍．卵磷脂胆固醇酰基转移酶活性的简易测定法．上海第一医学院学报，1985；12(2)：155～156
3．季宇彬．中药有效成分药理与应用，黑龙江科学技术出版社．1994
4．凌树森，张菊，孙维林．小鼠高胆固醇血症快速造型法的研究．药学通报，1985；70(1)：15
5．杨军，王静，等．降脂冲剂调脂作用实验研究．中草药，1997；28(4)：225～228
6．叶应妩等．全国临床检验操作规程，东南大学出版社．1997年第二版：268～275
7．韩志钧等．全国临床化学常用项目自动化分析法，辽宁科学技术出版社．1991年第一版：162～182
8．陈人俊等．常用医学检验，江西高校出版社．1993年第一版：3～107
9．王抒，等．血清LDL-C测定—介绍PVS法及Friedewald计算法的评价．中华医学检验杂志，1991；14：66
11．中华医学检验杂志，1987：10(4)：209
12．中华医学检验杂志，1991：2
13．赵晖，李宗友．黄芪桂枝五物汤加红参抗高血脂作用的实验研究．国外医学中医中药分册，2000；22(2)：83～87
14．王克勤，王大宝，陈保生．脂蛋白代谢的研究．生物化学与生物物理学报，1984：16(4)：329～335
15．上海市医学化验所．临床生化检验，上海科学技术出版社：197～198
16．陈瑗．周玫．脂质过氧化作用与动脉粥样硬化．生物化学和生物物理学进展，1989：16(4)：278
17．张洪渊等．生物化学教程，四川大学出版社．1994年第二版；374～404
18．徐淑云等．药理实验方法学，人民卫生出版社．2002年第三版；1189～1201
19．萨姆命鲁克等：分子克隆实验指南，科学出版社．1992年第二版；
20．徐济民，蔡沛源，等．痰浊型冠心病与血脂水平关系的探讨．中西医结合杂志，1984，5(4)：265～267
21．程志清，龚一萍等．利湿化痰祛淤补肾冲剂对实验性高脂模型作用的拆方研究．河北中医，1998，20(5)：320～322
22．姜传仓，蔡海江等．用两性毒素B-细胞模型法筛选胆固醇内源性合成以致剂．中西医结果杂志，1989；9(10)：604-606
23．张冰，李云谷等．菊苣醇提取物对实验性高糖高脂家兔血糖血脂及血液流变性的影响．北京中医药大学学报，1998；21(6)：16～19
24．齐刚等．绞股蓝总皂甙抗粥样动脉硬化机制研究．中国中药志．1996，21(9)：153～156
25．郑仕富，钟毅，朱秉匡．益寿调脂片对血液流变性及血脂的影响．微循环技术杂志，1997；2：75～76
26．林秋实，陈吉棣．山楂及山楂黄酮预防大鼠脂质代谢紊乱的分子机制研究．营养学报，2000；2(22)：131～136．
27．仇兴标，冯久贤，等．降胆固醇药物对冠脉硬化病人低密度脂蛋白受体基因表达的影响．上海医学，2000；9(23)：567～569．
28．刘萍，张静生，等．中药对低密度脂蛋白受体基因表达的影响．中国中西医结合急救杂志，2000：3(7)：141～144
29．秦树存，王士雯，程云．反转录—多聚酶链反应技术定量检测人外周血单个核白细胞低密度脂蛋白受体基因表达．中国动脉硬化杂志，1996；4(2)：141～143
30. Malkonen M, et al. Failure of thyroid hormones to maintain the normal lipoprotein pattern in rats after removal of the pictuitary gland. Atherosclerosis,1989; 38: 121
31. Analytical Biochemistry 142, 1984; 290～296
32. Vladimirov YA Free radical, aging and degeneration disease Alan Rliss, New York. 1986; 141
33. einecke JW Free radical biology and medicine Alan Rliss, New York, 1987; 65
34. Slater TF Free-radical mechanismin tissue injury Biochem J. 1984; 222:1
35. Malkonen M, et al. Failure of thyroid hormones to maintain the normal lipoprotein pattern in rats after removal of the pictuitary gland. Atherosclerosis, 1989; 38:121
36. Seteinberg D. Lipoprotein and the pathogenesis of atherosclerosis [J]. Cholesterol cardiovasc dis, 1987; 76(3): 508～513.
37. Brown MS, Goldstein JL. A receptor-mediated pathway for cholesterol homeostasis [J]. Science, 1986; 232:34～47
38. Sorci-Thomas M, Hendricks C L, Kearos M W. HepG2 cell LDL receptor activity and the accumlation of apol; porotein B and E in response to docosabexaenoic acid and cholesterol [J]. J Lipid Res. 1992; 33(8): 1147～1156
39. Rubin EM, et al. Nature.1992; 353:265
40. Zhang SH, et al.Curr Opin Lipidol. 1992; 258:468
41. Taylor J, et al. Nature. 1993; 4:84
42. LawnRM, et al. Nature. 1992; 360:670
43. Luc G, Fruchart JC. Am Jclin Nutr. 1991; 53:2065
44. Strickland DK, et al. J. Biol. Chem.1990; 265:17401
45. ToddPA,et al. Drugs. 1990; 40:583
46. O'ConnorP, et al. Druginvest.1992; 4:227
47. Helen TL, Diago Rs, Joseph AP, et al. J. Med Chem.1996; 39:5031
48. Cotton F. JAMA.1993; 270:2269
49. Steinberg D. Lipoprotein and the pathogenesis of atherosclerosis [J]. Cholesterol cardiovasc dis, 1987; 76(3): 508～513
50. Brown MS, Goldstein JL. A receptor-mediated pathway for cholesterol homeostasis [J]. Anal Biochem, 1986; 232:34～47
51. Elstner EF, Heupel A. Inbition of nitrite formation from hydrocylamine-onium-chloride: a sample assay for superoide dismutase [J]. Anal
Biochem, 1976; 700:616～621
52. Rajapaksha WRAKJS, Robertson L, Shaughnessy P J O'. As an internal control the housekeeping gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was amplified using primers base on the human sequence [J]. Mol Cellular Endocrinol, 1996; 120(1):25～30
53. Kovanen P T, Goldstein J L, Brown MS. Increased binding of low density lipoprotein to live membranes form rats treated with 17-a-ethylnylestradiol [J]. J Biol chem, 1979; 253:5126～5132
54. Ruding M J, peterson C O. A simple binding assay for the determination of low lipoprotien receptors in cell homogenates [J]. Biochimica Et Biophysica Acta, 1985; 833:359～365
55. Jung-Testas L, Weintraub H, Dupuis D, et al. Low density lipoprotein receptors in primary cultures of rat glial cells [J]. J Steroid Biochem Mol Biol, 1992, 42(6): 597～605
56. Cosgrove P G, Gaynor B J, Harwood H J Jr, Measurement of total hepatic low density lipoprotien receptor levels in the hamster [J]. J Lipid Res, 1993.34(11): 1983～2003
57. Sorci-Thomas M, Hendricks C L, Kearons M W. HepG2 cell LDL receptor activity and the accumulation of apol; poprotien B and E in response to docosahexaenoic acid and cholesterol [J]. J Llipid Res. 1992; 33(8): 1147～1156
58. Spady D K, W oolett L A. Interaction of dietary saturated and polyunsaturated triglyunsaturated trigycerides in regulating the processed that determine plasma low density lipoprotein concentrations in the rat [J]. J Lipid Res. 1990: 31(10): 1809～1819
59. Kovanen P T, Brown M S, et al. Saturation and suppression of hepatic lipoprotein receptor-a mechanism for the hypercholesterolemia of cholesterol fen rabbits [J]. Proc Natl Acad Sci USA, 1981; 78:1396～1405
60. Spady D K, Dietschy J M. Interaction of dietary cholesterol and triglyceride in the regulation of hepatic LDL transport in the hamster [J]. J Clin Invest, 1988; 81: 300～315
61. Sigh V, Kaul S, Chander R, et al. Stimulation of LDL renceptor activity in liver menbranes of guggulsterone treated rats [J]. Pharmacol Res, 1991; 22:37～50
62. Patsch, J R. et al. Formation of high density lipoprotein-like particles during lipolysis of very low density lipoprotein in vitro. Proc. Nat. Acad. Sci, 1978; 75:4519
63. Deckelbaum, R, et al. In vitro production of human plasma low density lipoprotein-like particles. J Biol Chem, 1979; 245:6079
64. Greten, H, et al. Measurement of two plasma triglyceride lipases by a immunochemical methods: Studies in patianes with hypertriglyceridemia. J Lipid Res, 1976; 17:203
65. Nikkila, E. et al. Post heparin plasma lipoprotein lipase and hepatic lipase in diabetes mellitus. Diabetes,1977; 26:11
66. Muller, P. et al. Htpertriglyceridemia secondary to liver desease. Eur J Clin Invest. 1974; 4:419
67. Bengtsson, C and Olivercrona, T. Interaction of lipoprotein lipase from bovine skim milk. J Biol Chem. 1977; 167:109
68. Numano F, Cyclic nucleotides and atheroclerosis In Cyclic mucleotides and therapeutic perspectives, 1979; 24:137
69. Muller S. Donner M, Dordin P. et al. Lipid fluidity of erythrocyte membrance; Failure tu demnonstrate significant atterations diabetes mellitus. Clinical Hemorhelegy, 1987: 7:619～626
70. Assmern G, Lipid metablism and atherosclerosis. Schattauer Verage, 1982: 67～75
71. Portman RJ, Scoott RC, et al. Decreased low density lipoprotein receptor function and mRNA level in lymphocytes from uremic patients. Kilney Laternational, 1992: 42:233～246
72. Jennifer AC, Ruswell DW, Lipsky PE. Regulation of low density lipoprotein receptor gene expression in human lymphocytes. J Biol Chem, 1989: 246(2): 298～304
73. Schmitz G, Bruning T, Kovacs E, et al. Flyorescence flow cytometry of human
liukocytes in the detection of LDL-receptor defects in the differential diagnosis of hypercholesterolemia, Arterioscter Thromb, 1993; 13:53～65
74. Brown MS, Goldstein JL. A receptor mediated pathway for momeostasis. Science, 1986; 2:32～34
75. Sambrook J. Fritsch EF, Maiatis T. eds. Molecular cloning: A labortory manual. 2nd ed. New York, 1989; 7:39～52
76. Anderson, J W, et al. The different dietary fibers have significantly different effects on serum and liver lipids of cholesterol-fed rats. J Nutr, 1994; 124:78
77. Hiroshi Hara, et al. Artificial fiber complexes composed of cellulose and guar gum or psyllium may be better sources of solubie fiber for rats than comparable fiber mixtures. J Nurr, 1994; 124:1238
78. Satya S J, et al. Plasma total and lipoprotein cholesterol, liver cholesterol and gecal cholesterol excretion in hamsters fed fiber diets. J Nutr, 1993; 123:1377
79. Zilvermit DB. A Proposal linking atheragenesis to the I interaction of enclothelial lipoproteins. Circ Res, 1973; 33:63
80. Greten H Degrella R and Klose G. Measurement of two plasma triglyceride lipase by an immunochemical method. J Lipid Res, 1976; 17:203
81. Nikkila E. Charaterization of the serum lipoproteins and their apoproteins in hypercholesterolacmic man. Diabetes, 1977; 26:11
82. Vladimirov YA Freeradical biology and medicine Alan Rliss, New York, 1986: 141
83. Roberts MJ, et al. Transient release of lipid Peroxides after coronary artery ballon angioplasty. Lancet, 1990; 21:143
84. Oda H, Keane WF. Lipids in pogression of renal disease. Kideny, 1997: 52: 36～38
85. Ruan XZ, Vaghese Z, Femando R, et al. Cytokine regulation of low density lipoprotein receptor gene transcription in human mesangial cells. Nephrol Dial Transpl, 1998; 13:1391～1397
2．蒋宪成，庄庆祺，梅美珍．卵磷脂胆固醇酰基转移酶活性的简易测定法．上海第一医学院学报，1985；12(2)：155～156
3．季宇彬．中药有效成分药理与应用，黑龙江科学技术出版社．1994
4．凌树森，张菊，孙维林．小鼠高胆固醇血症快速造型法的研究．药学通报，1985；70(1)：15
5．杨军，王静，等．降脂冲剂调脂作用实验研究．中草药，1997；28(4)：225～228
6．叶应妩等．全国临床检验操作规程，东南大学出版社．1997年第二版：268～275
7．韩志钧等．全国临床化学常用项目自动化分析法，辽宁科学技术出版社．1991年第一版：162～182
8．陈人俊等．常用医学检验，江西高校出版社．1993年第一版：3～107
9．王抒，等．血清LDL-C测定—介绍PVS法及Friedewald计算法的评价．中华医学检验杂志，1991；14：66
11．中华医学检验杂志，1987：10(4)：209
12．中华医学检验杂志，1991：2
13．赵晖，李宗友．黄芪桂枝五物汤加红参抗高血脂作用的实验研究．国外医学中医中药分册，2000；22(2)：83～87
14．王克勤，王大宝，陈保生．脂蛋白代谢的研究．生物化学与生物物理学报，1984：16(4)：329～335
15．上海市医学化验所．临床生化检验，上海科学技术出版社：197～198
16．陈瑗．周玫．脂质过氧化作用与动脉粥样硬化．生物化学和生物物理学进展，1989：16(4)：278
17．张洪渊等．生物化学教程，四川大学出版社．1994年第二版；374～404
18．徐淑云等．药理实验方法学，人民卫生出版社．2002年第三版；1189～1201
19．萨姆命鲁克等：分子克隆实验指南，科学出版社．1992年第二版；
20．徐济民，蔡沛源，等．痰浊型冠心病与血脂水平关系的探讨．中西医结合杂志，1984，5(4)：265～267
21．程志清，龚一萍等．利湿化痰祛淤补肾冲剂对实验性高脂模型作用的拆方研究．河北中医，1998，20(5)：320～322
22．姜传仓，蔡海江等．用两性毒素B-细胞模型法筛选胆固醇内源性合成以致剂．中西医结果杂志，1989；9(10)：604-606
23．张冰，李云谷等．菊苣醇提取物对实验性高糖高脂家兔血糖血脂及血液流变性的影响．北京中医药大学学报，1998；21(6)：16～19
24．齐刚等．绞股蓝总皂甙抗粥样动脉硬化机制研究．中国中药志．1996，21(9)：153～156
25．郑仕富，钟毅，朱秉匡．益寿调脂片对血液流变性及血脂的影响．微循环技术杂志，1997；2：75～76
26．林秋实，陈吉棣．山楂及山楂黄酮预防大鼠脂质代谢紊乱的分子机制研究．营养学报，2000；2(22)：131～136．
27．仇兴标，冯久贤，等．降胆固醇药物对冠脉硬化病人低密度脂蛋白受体基因表达的影响．上海医学，2000；9(23)：567～569．
28．刘萍，张静生，等．中药对低密度脂蛋白受体基因表达的影响．中国中西医结合急救杂志，2000：3(7)：141～144
29．秦树存，王士雯，程云．反转录—多聚酶链反应技术定量检测人外周血单个核白细胞低密度脂蛋白受体基因表达．中国动脉硬化杂志，1996；4(2)：141～143
30. Malkonen M, et al. Failure of thyroid hormones to maintain the normal lipoprotein pattern in rats after removal of the pictuitary gland. Atherosclerosis,1989; 38: 121
31. Analytical Biochemistry 142, 1984; 290～296
32. Vladimirov YA Free radical, aging and degeneration disease Alan Rliss, New York. 1986; 141
33. einecke JW Free radical biology and medicine Alan Rliss, New York, 1987; 65
34. Slater TF Free-radical mechanismin tissue injury Biochem J. 1984; 222:1
35. Malkonen M, et al. Failure of thyroid hormones to maintain the normal lipoprotein pattern in rats after removal of the pictuitary gland. Atherosclerosis, 1989; 38:121
36. Seteinberg D. Lipoprotein and the pathogenesis of atherosclerosis [J]. Cholesterol cardiovasc dis, 1987; 76(3): 508～513.
37. Brown MS, Goldstein JL. A receptor-mediated pathway for cholesterol homeostasis [J]. Science, 1986; 232:34～47
38. Sorci-Thomas M, Hendricks C L, Kearos M W. HepG2 cell LDL receptor activity and the accumlation of apol; porotein B and E in response to docosabexaenoic acid and cholesterol [J]. J Lipid Res. 1992; 33(8): 1147～1156
39. Rubin EM, et al. Nature.1992; 353:265
40. Zhang SH, et al.Curr Opin Lipidol. 1992; 258:468
41. Taylor J, et al. Nature. 1993; 4:84
42. LawnRM, et al. Nature. 1992; 360:670
43. Luc G, Fruchart JC. Am Jclin Nutr. 1991; 53:2065
44. Strickland DK, et al. J. Biol. Chem.1990; 265:17401
45. ToddPA,et al. Drugs. 1990; 40:583
46. O'ConnorP, et al. Druginvest.1992; 4:227
47. Helen TL, Diago Rs, Joseph AP, et al. J. Med Chem.1996; 39:5031
48. Cotton F. JAMA.1993; 270:2269
49. Steinberg D. Lipoprotein and the pathogenesis of atherosclerosis [J]. Cholesterol cardiovasc dis, 1987; 76(3): 508～513
50. Brown MS, Goldstein JL. A receptor-mediated pathway for cholesterol homeostasis [J]. Anal Biochem, 1986; 232:34～47
51. Elstner EF, Heupel A. Inbition of nitrite formation from hydrocylamine-onium-chloride: a sample assay for superoide dismutase [J]. Anal
Biochem, 1976; 700:616～621
52. Rajapaksha WRAKJS, Robertson L, Shaughnessy P J O'. As an internal control the housekeeping gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was amplified using primers base on the human sequence [J]. Mol Cellular Endocrinol, 1996; 120(1):25～30
53. Kovanen P T, Goldstein J L, Brown MS. Increased binding of low density lipoprotein to live membranes form rats treated with 17-a-ethylnylestradiol [J]. J Biol chem, 1979; 253:5126～5132
54. Ruding M J, peterson C O. A simple binding assay for the determination of low lipoprotien receptors in cell homogenates [J]. Biochimica Et Biophysica Acta, 1985; 833:359～365
55. Jung-Testas L, Weintraub H, Dupuis D, et al. Low density lipoprotein receptors in primary cultures of rat glial cells [J]. J Steroid Biochem Mol Biol, 1992, 42(6): 597～605
56. Cosgrove P G, Gaynor B J, Harwood H J Jr, Measurement of total hepatic low density lipoprotien receptor levels in the hamster [J]. J Lipid Res, 1993.34(11): 1983～2003
57. Sorci-Thomas M, Hendricks C L, Kearons M W. HepG2 cell LDL receptor activity and the accumulation of apol; poprotien B and E in response to docosahexaenoic acid and cholesterol [J]. J Llipid Res. 1992; 33(8): 1147～1156
58. Spady D K, W oolett L A. Interaction of dietary saturated and polyunsaturated triglyunsaturated trigycerides in regulating the processed that determine plasma low density lipoprotein concentrations in the rat [J]. J Lipid Res. 1990: 31(10): 1809～1819
59. Kovanen P T, Brown M S, et al. Saturation and suppression of hepatic lipoprotein receptor-a mechanism for the hypercholesterolemia of cholesterol fen rabbits [J]. Proc Natl Acad Sci USA, 1981; 78:1396～1405
60. Spady D K, Dietschy J M. Interaction of dietary cholesterol and triglyceride in the regulation of hepatic LDL transport in the hamster [J]. J Clin Invest, 1988; 81: 300～315
61. Sigh V, Kaul S, Chander R, et al. Stimulation of LDL renceptor activity in liver menbranes of guggulsterone treated rats [J]. Pharmacol Res, 1991; 22:37～50
62. Patsch, J R. et al. Formation of high density lipoprotein-like particles during lipolysis of very low density lipoprotein in vitro. Proc. Nat. Acad. Sci, 1978; 75:4519
63. Deckelbaum, R, et al. In vitro production of human plasma low density lipoprotein-like particles. J Biol Chem, 1979; 245:6079
64. Greten, H, et al. Measurement of two plasma triglyceride lipases by a immunochemical methods: Studies in patianes with hypertriglyceridemia. J Lipid Res, 1976; 17:203
65. Nikkila, E. et al. Post heparin plasma lipoprotein lipase and hepatic lipase in diabetes mellitus. Diabetes,1977; 26:11
66. Muller, P. et al. Htpertriglyceridemia secondary to liver desease. Eur J Clin Invest. 1974; 4:419
67. Bengtsson, C and Olivercrona, T. Interaction of lipoprotein lipase from bovine skim milk. J Biol Chem. 1977; 167:109
68. Numano F, Cyclic nucleotides and atheroclerosis In Cyclic mucleotides and therapeutic perspectives, 1979; 24:137
69. Muller S. Donner M, Dordin P. et al. Lipid fluidity of erythrocyte membrance; Failure tu demnonstrate significant atterations diabetes mellitus. Clinical Hemorhelegy, 1987: 7:619～626
70. Assmern G, Lipid metablism and atherosclerosis. Schattauer Verage, 1982: 67～75
71. Portman RJ, Scoott RC, et al. Decreased low density lipoprotein receptor function and mRNA level in lymphocytes from uremic patients. Kilney Laternational, 1992: 42:233～246
72. Jennifer AC, Ruswell DW, Lipsky PE. Regulation of low density lipoprotein receptor gene expression in human lymphocytes. J Biol Chem, 1989: 246(2): 298～304
73. Schmitz G, Bruning T, Kovacs E, et al. Flyorescence flow cytometry of human
liukocytes in the detection of LDL-receptor defects in the differential diagnosis of hypercholesterolemia, Arterioscter Thromb, 1993; 13:53～65
74. Brown MS, Goldstein JL. A receptor mediated pathway for momeostasis. Science, 1986; 2:32～34
75. Sambrook J. Fritsch EF, Maiatis T. eds. Molecular cloning: A labortory manual. 2nd ed. New York, 1989; 7:39～52
76. Anderson, J W, et al. The different dietary fibers have significantly different effects on serum and liver lipids of cholesterol-fed rats. J Nutr, 1994; 124:78
77. Hiroshi Hara, et al. Artificial fiber complexes composed of cellulose and guar gum or psyllium may be better sources of solubie fiber for rats than comparable fiber mixtures. J Nurr, 1994; 124:1238
78. Satya S J, et al. Plasma total and lipoprotein cholesterol, liver cholesterol and gecal cholesterol excretion in hamsters fed fiber diets. J Nutr, 1993; 123:1377
79. Zilvermit DB. A Proposal linking atheragenesis to the I interaction of enclothelial lipoproteins. Circ Res, 1973; 33:63
80. Greten H Degrella R and Klose G. Measurement of two plasma triglyceride lipase by an immunochemical method. J Lipid Res, 1976; 17:203
81. Nikkila E. Charaterization of the serum lipoproteins and their apoproteins in hypercholesterolacmic man. Diabetes, 1977; 26:11
82. Vladimirov YA Freeradical biology and medicine Alan Rliss, New York, 1986: 141
83. Roberts MJ, et al. Transient release of lipid Peroxides after coronary artery ballon angioplasty. Lancet, 1990; 21:143
84. Oda H, Keane WF. Lipids in pogression of renal disease. Kideny, 1997: 52: 36～38
85. Ruan XZ, Vaghese Z, Femando R, et al. Cytokine regulation of low density lipoprotein receptor gene transcription in human mesangial cells. Nephrol Dial Transpl, 1998; 13:1391～1397