Guinea pigs as models to study the hypocholesterolemic effects of drugs.
Guinea pigs as models to study the hypocholesterolemic effects of drugs.
复制标题
DOI：
10.1111/j.1527-3466.2004.tb00131.x
复制
发表时间：
2006-06
期刊：
影响因子：
--
通讯作者：
K. L. West;M. Fernández
中科院分区：
文献类型：
--
作者：
K. L. West;M. Fernández
未标记豚鼠是研究药物降胆固醇作用机制的有用模型。和人类一样，豚鼠是少数携带LDL中大部分胆固醇的物种之一。这种动物模型也被证明在高胆固醇饮食的挑战下会发生动脉粥样硬化。此外，男性、女性和切除卵巢的豚鼠（绝经模型）的血浆脂质谱与在人类中观察到的相似。在本报告中，旨在降低血浆胆固醇和甘油三酯在高脂血症患者的药物进行了综述。研究分析了HMG-CoA还原酶抑制剂、酰基CoA胆固醇酰基转移酶抑制剂、贝特类药物、胆汁酸树脂、胆汁酸转运蛋白尖钠抑制剂和其他药物的降血脂作用，结果表明豚鼠和人类对药物治疗的反应相当。此外，关于药物对LDL分解代谢或VLDL合成的特定影响的有限临床报告的结果与在豚鼠中的观察结果一致。综上所述，豚鼠显然是一个有用的动物模型，可以进一步探索降脂药物的作用机制，包括对参与胆固醇代谢的特定受体和调节酶的影响，以及对动脉粥样硬化早期发展的影响。ACAT，酰基辅酶a：胆固醇酰基转移酶；顶钠共依赖胆汁酸转运体；载脂蛋白B；冠心病，冠心病；CYP7，胆固醇7 -羟化酶；HDL，高密度脂蛋白；HMG-CoA， 3-羟基-3-甲基戊二酰辅酶A；FCR：自由分解代谢率；LDL，低密度脂蛋白；PPAR，过氧化物酶体增殖物激活受体；TC，总胆固醇；TG,甘油三酸酯;VLDL，极低密度脂蛋白。
UNLABELLED Guinea pigs are useful models to investigate the mechanisms of the hypocholesterolemic effects of drugs. Like humans, guinea pigs are one of the few species that carry the majority of cholesterol in LDL. This animal model has also been shown to develop atherosclerosis when challenged with hypercholesterolemic diets. In addition, plasma lipid profiles in males, females and ovariectomized guinea pigs, a model for menopause, follow similar patterns to those observed in humans. In this report, drugs aimed at lowering plasma cholesterol and triglycerides in hyperlipidemic individuals are reviewed. Studies analyzing the hypolipidemic effect of HMG-CoA reductase inhibitors, acyl CoA cholesterol acyltransferase inhibitors, fibrates, bile acid resins, apical sodium bile acid transporter inhibitors, and others show that guinea pigs and humans have comparable responses to drug therapy. In addition, results from the limited clinical reports addressing specific effects of drugs on LDL catabolism or VLDL synthesis are in agreement with observations in guinea pigs. From the review of these studies, it is apparent that the guinea pig is a useful animal model to further explore the mechanisms of action of lipid lowering drugs including effects on specific receptors and regulatory enzymes involved in cholesterol metabolism and on early atherosclerosis development. ABBREVIATIONS ACAT, acyl-CoA:cholesterol acyltransferase; ASBT, apical sodium co-dependent bile acid transporter; ApoB, apolipoprotein B; CHD, coronary heart disease; CYP7, cholesterol 7alpha-hydroxylase; HDL, high density lipoprotein; HMG-CoA, 3-hydroxy-3-methylglutaryl coenzyme A; FCR, free catabolic rate; LDL, low density lipoprotein; PPAR, peroxisome proliferators-activated receptor; TC, total cholesterol; TG, triglycerides; VLDL, very low density lipoprotein.