白化豚鼠与花色豚鼠高脂造模以及降脂药效学的比较

目的 比较分析白化豚鼠与花色豚鼠在构建高脂血症模型以及评价降脂药效学方面的差异，为高脂血症模型建立时豚鼠的品种选择提供参考。方法 选取5周龄的白化豚鼠和花色豚鼠测定基础血脂水平，具体包括总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白（HDL-C）和低密度脂蛋白（LDL-C）。随后分别随机分为正常组（12只）和高脂模型组（24只），正常组饲喂普通饲料，高脂模型组饲喂高脂饲料以构建高脂血症模型；饲喂4周后，同上测定血脂水平。进一步将高脂模型组随机分为匹伐他汀钙组（12只）和溶媒对照组（12只），匹伐他汀钙组每天灌胃给予匹伐他汀钙（1mg/kg），溶媒对照组每天灌胃给予同体积的溶媒，持续给药4周，并同步饲喂高脂饲料；给药结束后，同上测定血脂水平。结果 当给予普通饲料喂养时，白化豚鼠血脂较为稳定，随周龄增长没有显著变化，而花色豚鼠的TC和LDL-C在9周龄后才比较稳定。当给予高脂饲料喂养时，白化豚鼠的TC、TG和LDL-C在造模的四周时间内迅速上升，且增幅显著大于花色豚鼠，HDL-C与花色豚鼠的变化幅度相似。运用模型组豚鼠，进行降脂药效学的考察，匹伐他汀在白化豚鼠高脂血症模型中降脂（TC、TG和LDL-C）幅度更大、升高HDL-C的作用更显著。结论 在选用正常豚鼠评价降脂作用时，降TG或升HDL-C类药物宜选用5周龄之后的白化豚鼠，降TC或LDL-C类药物宜选用9周龄之后的花色豚鼠；在选用高脂血症豚鼠模型评价降脂作用时，白化豚鼠较花色豚鼠在造模后的血脂水平更加紊乱，且对降脂药物的敏感程度更高，故可作为构建高脂血症模型和评价降脂药效学研究较佳的实验动物。

Comparison of a Hyperlipidemic Model and the Pharmacodynamics of Lipid-lowering among Albino Guinea Pigs and Pigment Guinea Pigs

Objective To compare the differences of two stocks of guinea pigs, the albino guinea pigs and pigment guinea pigs, in establishing the dyslipidemic model and evaluating the lipid-lowering action, the properties of the different guinea pigs for hyperlipidemia are systemically evaluated. Methods Two stocks of 5-week-old guinea pigs, the albino guinea pigs and pigment guinea pigs, were randomly divided into two groups, normal group (NC) and model group (Model). For NC group, 12 of guinea pigs were fed with normal chew. For Model group, after fed with high-fat diet for four weeks, 24 male guinea pigs were randomly grouped and treated with vehicle (VC group) and pitavastatin (Pit group) calcium by gavage as well as received high-fat diet. Before and after modeling and pitavastatin treatment, the blood samples were collected and subjected to analysis for plasma parameters of TC, TG, HDL-C, LDL-C, Glu, ALT, AST, BUN and CREA levels, respectively. Result In normal group, the blood lipid levels of albino guinea pigs were more stable than that of the pigmented pigs with the increase of age. After fed with high-fat diet, the plasma lipid levels of TC, TG and LDL-C significantly increased in two strains of guinea pigs, while HDL-C indicated a decrease at varied degree. Interestingly, lipid disorder in albino guinea pigs was significantly higher than that of pigment guinea pigs. And also, after drugs administration for four weeks, pitavastatin treatment significantly greater decreased the high-fat elevated lipid level of TC, TG and LDL-C in albino guinea pigs compared to pigment guinea pigs. Conclusion The two stocks of uinea pigs, the albino guinea pigs and pigment guinea pigs, demonstrated different properties in establishing dyslipidemic model and evaluating pharmacodynamics of the lipid-lowering; however, compared to pigment guinea pigs, the albino guinea pigs have obvious superiorities because of easily establishing hyperlipidemia model and reasonably evaluating lipid-lowering actions of drugs.