五指山小型猪动脉粥样硬化模型的建立

The Diet-Induced Atherosclerosis In Wuzhishan Minipigs

目的建立五指山小型猪动脉粥样硬化模型，探讨小型猪动脉粥样硬化模型复制规范。方法3～4月龄五指山小型猪30头，随机分为3组：对照组6头，喂基础饲料；实验组分别饲喂含1．5％胆固醇的高脂饲料（T1组）和含3．0％胆固醇的高脂饲料（T2组）。实验过程中进行一般临床观察和血脂相关指标检查，在实验后4、6、8和12个月，实验组分别处死动物3头，对照组分别在实验后6个月和12个月各处死3头，对动物的心血管系统和主要脏器做病理学检查。结果高胆固醇、高脂饲料能够引起五指山小型猪血清胆固醇指标升高和动脉粥样硬化病变形成。实验组血清LDL-C、TC和HDL-C值在实验后1个月显著升高，升高幅度最高分别达到对照组的13．3～15．0倍、8．2～10．2倍和3．3～4．2倍。在实验后4个月，实验组动物均出现明显的早期动脉粥样硬化病变，至6个月和8个月，动脉病变逐渐加重，最严重的病变可达病理分级的Ⅳ级。至实验后12个月，在动物的大、中动脉观察到广泛的病变，最严重部位达到病理分级的V级。动脉病变易发且严重的部位为腹主动脉、髂动脉和冠状动脉，动脉病变少见且较轻的部位为颈总动脉、肠系膜总动脉和肾动脉。血脂相关指标的升高幅度、动脉病变的出现时间和严重程度T2组比T1组略重，但是差异不十分显著。结论小型猪食饵性动脉粥样硬化模型的诱导配方中，胆固醇含量以1．5％～2．0％为宜，观察早期动脉病变诱导时间需要4至8个月，晚期病变则需要12个月以上的诱导时间。

Objective To induce atherosclerosis in Wuzhishan minipigs, and establish the formula of experimental atherosclerosis in the minipigs. Methods Thirty Wuzhishan minipigs were randomized to 3 groups, one group of 6 animals was set as control, the other 2 groups of 12 animals each were set as test groups fed with 1.5% cholesterol, high-fat diet （group T1 ） and 3.0 % cholesterol, high-fat diet （group T2）, respectively. The serum TG, TC, LDL-C and HDL-C were analysed monthly. At months 4, 6, 8 and 12 after high-cholesterol, high-fat diet feeding, three swine in each test group were subjected to a full gross necropsy to exam the atherosclerosis by macroscopic and microscopic evaluation. Three animals from the control group were necropsied at months 6 and 12. Results After feeding with the high-cholesterol, high-fat diet, the values of cholesterol were elevated significantly and the atherosclerosis lesions were observed in swines. The mean values of LDL-C, TC and HDL-C were increased significantly after 1 month high cholesterol feeding, and were approximate 13 - 15 folds, 8 - 10 folds and 3 - 4 folds respevtively comparing to the control group at months 3 and 4. Most of the atherosclerosis lesions were found in abdominal aorta, iliac artery, an coronary artery, and were seldomly distributed in other examined arteries, after 4 ~ 8 months high-cholesterol feeding. The atherosclerosis lessions were more extensive and severe after 12 months administration. The abdominal aorta, iliac and coronary arteries were the region most severely involved by fibrosis and intimal thickening. The carotid, mesenteric and kidney arteries were slightly involved area and free of atherosclerosis at early period. Group T2 has higher serum LDL-C, TC and HDL-C values, and more severe atherosclerosis than group T1, but the differences were slightly. Conclusion 1.5 % - 2.0% cholesterol in high-fat feed is reasonable for inducing atherosclerosis in minipigs. To study primary atherosclerosis need 4 - 8 months high-cholesterol, high-fat feeding, and 12 months should cost for research secondary atherosclerosis in minipigs.