1 首都医科大学宣武医院心脏内科，国家老年疾病临床医学研究中心，北京 100053
2 北京市房山区良乡医院内分泌科，北京 102501
目的：通过给予巴马小型猪高脂饮食，低剂量链脲菌素联合球囊拉伤的方法，构建糖尿病冠状动脉粥样硬化模型。方法：将18头4月龄健康雄性巴马小型猪随机分为对照组(n=3)和模型组(n=15)。对照组以普通饲料喂养；模型组以高脂饲料喂养，静脉注射链脲菌素(100 mg/kg)后持续监测葡萄糖2周，第3周行右冠状动脉中段球囊拉伤术，第20周随机处死3只，取右冠状动脉球囊拉伤段、未拉伤的左冠状动脉回旋支、颈动脉、肾动脉和胰腺做病理组织学检查。结果：模型组12只动物达到糖尿病标准并存活至第20周。与对照组相比，模型组动物体重明显下降，血糖、总胆固醇、低密度脂蛋白胆固醇和三酰甘油水平明显升高(P<0.05)。模型组动物右冠状动脉球囊拉伤段血管内膜增生程度明显高于未拉伤左冠状动脉回旋支和对照组右冠状动脉(P<0.05)。模型组动物胰岛数目和胰岛细胞数目较对照组明显减少(P<0.05)。第36周模型组其余9只动物状态良好。结论：低剂量链脲菌素联合球囊拉伤可加速巴马小型猪模型糖尿病冠状动脉粥样硬化，具有较高的成功率、良好的安全性和长期的有效性。关键词： 糖尿病；动脉粥样硬化；链脲菌素；球囊拉伤；巴马小型猪；动物模型
Establishment of pig model of coronary atherosclerosis with diabetes mellitus
CorrespondingAuthor: XIA Jinggang Email: firstname.lastname@example.org
Foundation: This work was supported by National Natural Science Foundation of China (81770344).
Objective: A diabetic coronary atherosclerosis model was established by giving Bama minipigs high-fat diet, low dose streptozotocin combined with balloon injury. Methods: Eighteen healthy male Bama minipigs, aged 4 months old, were randomly divided into a control group (n=3) and a model group (n=15). The pigs in the control group were given normal diet. In the model group, pigs were fed with high-fat diet and intravenously injected with streptozotocin (100 mg/kg) followed by continuous glucose monitoring for 2 weeks, and a balloon injury was performed in the middle segment of right coronary artery at 3 weeks. Three pigs in the model group were randomly euthanized at 20 weeks, and the injured right coronary artery, uninjured circumflex coronary artery, carotid artery, renal artery, and pancreas were taken for histopathological examination. Results: Twelve pigs in the model group reached the diabetic standard and survived to the 20th week. Compared with the control group, body weight of the model group significantly decreased, and the levels of blood glucose, total cholesterol, low-density lipoprotein cholesterol, and triglyceride significantly increased (P<0.05). Significant intimal proliferation of the right coronary artery was shown in the balloon-injured vessels compared with the uninjured vessels in the model group and the right coronary artery in the control group (P<0.05). The number of islets and islet cells in the model group significantly decreased compared with those in the control group (P<0.05). At 36 weeks, the other 9 pigs in the model group were still in good condition. Conclusion: Low dose streptozotocin combined with balloon injury can accelerate the diabetic coronary atherosclerosis in Bama minipig model with high success rate, good safety, and long-term effectiveness.Keywords： diabetes mellitus; atherosclerosis; streptozotocin; balloon injury; Bama minipigs; animal model