摘要
目的建立应用蕨麻小型猪建立心肌梗死(心梗)的造模方法和具有临床意义的模型指标,探讨心梗边缘区的基因表达与代谢失偿的相关性。方法选取13只雄性蕨麻小型猪,随机分组,其中假手术对照组和心梗手术组各5只,不经任何手术处理的正常对照组3只。麻醉后在左前冠状动脉行靠近心尖的三分一降支主干支进行永久性结扎形成心肌缺血、梗死。术后4周进行心功能超声检测、采血并进行血清生化分析;安乐死后取梗死边缘区进行病理和基因芯片分析。结果超声图可见明显的心梗区域,数据显示心梗手术组的收缩末期左心室腔射血分数及短轴缩短率较假手术组分别降低32%和40%;血清中有谷草转氨酶、血清胆红素、乳酸脱氢酶等升高;病理切片显示梗死边缘区域的心肌纤维断裂、溶解,结缔组织增生,中性粒细胞和淋巴细胞增多;基因表达谱分析显示在梗死边缘区有2个调控心梗后重构和组织病理通路,3个炎症和免疫调节通路,8个脂肪、蛋白、糖能量代谢途径的基因表达有显著性改变。结论成功建立了蕨麻小型猪的心梗模型,其冠状动脉分支少,便于手术且成模稳定性,模型表征可与临床指标相吻合;模型梗死边缘区的基因表达谱特征与临床上代谢失偿表现有相同变化趋势,为心梗机理的研究提供了实验动物模型及心梗边缘区的具有参考价值的特征性改变。
Objective To establish a Juema minipig model of myocardial infarction,to evaluate the clinical indices in the model pigs,and to explore the relationship between gene expression and metabolic decompensation. Methods 13 male Juema minipigs were randomly divided into control（ Sham,n = 5）,myocardial infarction（ MI,n = 5） and normal control（ for evaluating the recovery condition after surgery,n = 3） groups. In the MI group,the ligation was done at the left descending coronary artery around the 1 /3 distance to heart apex. Four weeks after the surgery,the cardiac function and serum biochemistry was analyzed. The histological changes and gene expression profiles in the myocardium in the periinfarct area were exanimated. Results Ultrasonic images showed that the infarction was formed,the ejection fraction and fraction shortening were significantly reduced in the MI group（ ～ 32% and ～ 40% less than those of the sham group）.Histological examination showed that myocardial fibers at the peri-infarct area were broken,dissolved,and there was connective tissue hyperplasia with increased neutrophil and lymphocyte infiltration. Microarray analysis revealed that two myocardial remodeling and pathology mediating pathways,three inflammation-related pathways,and 8 metabolic pathways（ including fatty acid,amino acid,and glucose metabolic pathways） were significantly changed. Conclusions We have successfully established a Juema minipig model of myocardial infarction. The less branches of the left descending coronary artery allow us to establish a stable model by surgery with comparable characteristics in the clinic indices. The results of this study provides useful reference characteristics of an animal model with characteristic changes in the peri-infarct area.
作者
谭伟江
王静
李想
李小辉
雷迁
黄家园
龚宝勇
李菁
陈智英
王剑
陈小红
王希龙
杨丰华
黄韧
TAN Wei-jiang WANG Jing LI Xiang LI Xiao-hui LEI Qian HUANG Jia-yuan GONG Bao-yong LI Jing CHEN Zhi-ying WANG Jian CHEN Xiao-hong WANG Xi-long YANG Feng-hua HUANG Ren(Guangdong Provincial Key Laboratory for Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute, Guangzhou 510663, China Guangdong Pharmaceutical University, Guangzhou 510063 Jinan University, Guangzhou, 510632 Department of Anesthesiology, Sichuan Academy of Medical Sciences ＆ Sichuan Provincial People＇ s Hospital, Chendu 610072 Zhongshan Hospital Fudan University, Shanghai 200032)
出处
《中国实验动物学报》
CAS
CSCD
北大核心
2016年第6期558-566,共9页
Acta Laboratorium Animalis Scientia Sinica
基金
广东省科技专项(No.2016A020216019)
广东省实验动物重点实验室(No.2013A061402001)
国家自然科学基金-面上项目(No.31572351)
国家自然科学基金-青年科学基金项目(No.81500281)
广东省科技专项(No.2015A030302035)
关键词
蕨麻小型猪
心肌梗死模型
模型评价
梗死边缘区
基因表达谱
Juema minipig
Myocardial infarction model
Model evaluation
Peri-infarct area
Gene expression profile
