浙江省自然科学基金（LY12C04002）；浙江省卫生高层次创新人才培养工程项目。
目的 观察高脂诱导对藏猪糖脂代谢和粥样斑块形成的影响，探讨藏猪胰岛素抵抗动脉粥样硬化模型的病症特点。方法 取4～5月龄藏猪随机分为正常对照组4只饲喂普通饲料、AS模型组共8只饲喂高脂饲料，连续造模24周。检测造模前、造模后4、8、12、16、20、24周的空腹血糖、果糖胺、血脂、血清胰岛素含量测定和糖耐量试验，并计算动脉硬化指数（AI）、胰岛素抵抗指数（HOMA-IR）和胰岛素敏感指数（HOMA-IS）。造模后24周，测定麻醉状态下动脉血压和左心室功能指标，并取主动脉进行大体观察和HE染色及油红“O”染色。结果 与正常对照组比，AS模型组从第16周开始空腹血糖显著升高（P < 0.05，P < 0.01），果糖胺从第4周起即发生显著升高（P < 0.01）血脂水平亦在造模第4～24周时升高显著（P < 0.01），AS模型组藏猪在第4～24周期间AI显著上升（P < 0.05，P < 0.01），造模第16～24周HOMA-IR亦显著升高（P < 0.05，P < 0.01），HOMA-IS则显著降低（P < 0.05）。第24周时，AS模型组MBP和SBP显著升高（P < 0.05，P < 0.01），LVEDP、+dp/dtmax、-dp/dtmax较正常组均发生显著性改变（P < 0.05，P < 0.01），病理学观察显示模型组出现明显的脂质沉积和粥样硬化形成。结论 藏猪高脂饲料诱导后能形成明显的动脉粥样硬化，并伴有高血压、高血脂、糖耐量异常等胰岛素抵抗症状，是研究的胰岛素抵抗动脉粥样硬化的理想的实验动物。
Objective To observe the effect of high fat diet on the lipid metabolism and the formation of atherosclerosis in Tibetan Pig in order to discuss the characteristics of the insulin resistance atherosclerosis model of Tibetan Pig. Method Several 4-5 months age Tibetan Pigs were randomly divided into normal group 4 ones which were fed with common diet and AS model group 8 ones which were fed with high fat diet for 24 weeks. At the time of before the modeling and the 4th、8th、12th、16th、20th、24th week blood was regularly taken from precaval vein, then measured fasting plasma glucose, fructosamine, blood lipid and serum insulin level and conduct glucose tolerance test, calculated the atherogenic index(AI), insulin resistance index(HOMA-IR), insulin sensitivity index(HOMA-IS). Animals were anesthetized to meare arterial blood pressure and indices of left ventricular function. Abdominal aortic was taken to observe the plaque, HE staining and oil red "O" staining was conducted to observe the pathological changes. Result Controlled with normal group, the fasting plasma glucose of AS model group increased significantly since 16th week(P < 0.05,P < 0.01), the fructosamine increased significantly since 4th week(P < 0.01), the lipid level also increased significantly from 4-24th week, atherogenic index(AI) increased significantly from 4-24th week. During the 16-24th week the HOMA-IR of the model group was significantly high and the HOMA-IS was significantly low(P < 0.05,P < 0.01). At the 24th week, controlled with the normal group, the MBP and SBP of the model group was significantly high(P < 0.05,P < 0,01) while the LVEDP、+dp/dtmax、-dp/dtmax was significantly changed(P < 0.05,P < 0.01). Pathological observation showed that in the AS model group there is lipid deposition and atherosclerosis appeared. Conclusion Tibetan Pig induced by high fat diet can appear obvious atherosclerosis and insulin resistance, hypertension, hyperlipidemia, impaired glucose tolerance, which is an ideal experimental animal of the study of insulin resistance atherosclerosis.
马毅超,潘永明,陈亮,陈方明,杨涛涛,陈民利.胰岛素抵抗动脉粥样硬化小型猪模型的研究[J].中国比较医学杂志,2014,24(1):12~17,11.
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