糖尿病和心血管病相关的重要靶点基因PPARγ过表达转基因克隆猪模型的建立  

Establishment of transgenic pig model of PPAR γ overexpression,an important target gene related to diabetes mellitus and cardiovascular disease

作　　者：吴彩霞 刘朝明 颜泉梅 张全军 欧阳振 赵宇 樊娜娜 赖良学 WU Cai-xia;LIU Chao-ming;YAN Quan-mei;ZHANG Quan-jun;OUYANG Zhen;ZHAOYu;FAN Na-na;LAI Liang-xue(Guangzhou Institute of Biomedicine and Health,ChineseAcademy of Sciences,Guangzhou510530,China;College of Animal Medicine,Jilin University,Changchun 130062,Chin)

机构地区：[1]中国科学院广州生物医药与健康研究院,广东广州510530 [2]吉林大学动物医学学院,吉林长春130062

出　　处：《中国兽医学报》2020年第7期1366-1371,共6页Chinese Journal of Veterinary Science

基　　金：国家重点研发计划基金资助项目(2017YFA0105100);国家973计划基金资助项目(2011CB944200);广东省科技计划基金资助项目(2019A030317010)。

摘　　要：动物模型是科学研究不可缺少的工具,特别是对于人类疾病相关的研究,受到取材和伦理道德的限制,很多研究无法直接在人体中进行,必须首先依靠动物模型进行广泛的试验和评估。猪的心血管系统在结构和功能上与人类非常相似,例如脉搏,在静息状态下,人的脉搏每分钟60~90次,猪的则为65~80次。猪的动脉循环系统几乎是人的动脉循环系统的复制品。目前,以猪作为动物模型来研究动脉粥样硬化和心肌梗塞等心血管疾病,是猪作为人类疾病模型应用最为成功的范例之一。PPARγ是噻唑烷二酮类药物的靶点,科学家们利用小鼠的研究结果表明,噻唑烷二酮类药物在治疗糖尿病的同时对心血管系统也有保护作用,但由于小鼠心血管系统与人类相差甚远,使得小鼠的研究结果与近年临床上观察到的病人心脏毒副作用不一致。因此,科学家们急需建立与人类更为接近的大动物模型来研究糖尿病及其心血管并发症,由于猪的心血管系统与人类接近,猪成为理想的研究糖尿病和心血管疾病的动物模型。我们共计构建了1100枚重构胚胎,分别移植到5头受体猪内,经B超鉴定3头怀孕,共计出生8头猪,经PCR鉴定8头全为阳性猪模型。结果表明我们利用体细胞核移植技术成功建立了糖尿病和心血管病相关的重要靶点基因PPARγ过表达转基因克隆猪模型。Animal models are indispensable tools for scientific research,especially for research related to human diseases.Due to restrictions on materials and ethical,many studies can not be carried out directly in the human body.It is necessary to rely first on animal models for extensive testing and assessment.The cardiovascular system of pigs is very similar in structure and function to humans,such as pulse.At rest,the pulse of people is 60-90 times per minute,and that of pigs is 65-80 times.The arterial circulatory system of pigs is almost a replica of the human arterial circulatory system.At present,using pigs as animal models to study cardiovascular diseases such as atherosclerosis and myocardial infarction is one of the most successful examples of pigs as human disease models.PPARγis the target of thiazolidadone drugs.Scientists use mouse research results to show that thiazolidadone drugs also have a protective effect on the cardiovascular system while treating diabetes,However,because the cardiovascular system of mice is far from human,the results of the mice are inconsistent with the clinically observed side effects of the patients in recent years.Therefore,scientists urgently need to establish a large animal model that is closer to humans to study diabetes and its cardiovascular complications.Since the cardiovascular system of pigs is close to that of humans,pigs are ideal animal models for studying diabetes and cardiovascular diseases.A total of 1100 reconstructed embryos were constructed and transplanted into five receptor pigs.After B ultrasound,three pregnancies were identified.A total of eight pigs were born,and identified by PCR as positive pig models.The results showed that we successfully established a PPARγoverexpression transgenic cloned pig model with important target genes related to diabetes and cardiovascular disease using somatic cell nuclear transfer technology.

关 键 词：糖尿病 心血管病 PPARΓ 转基因克隆 猪模型 

分 类 号：S852.1[农业科学—基础兽医学] S828[农业科学—兽医学]