小鼠横向主动脉弓缩窄与异丙肾上腺素注射构建心肌肥厚模型方法的比较  

Comparison of the methods of constructing myocardial hypertrophy model by transverse aortic arch coarctation and isoproterenol injection in mice

作　　者：曾文如 王东伟 邵晓奇 ZENG Wenru;WANG Dongwei;SHAO Xiaoqi(Institute of Chinese Medicine,Guangdong Pharmaceutical University,Guangzhou 510006,China)

机构地区：[1]广东药科大学中医药研究院,广东广州510006

出　　处：《广东药科大学学报》2023年第1期122-128,共7页Journal of Guangdong Pharmaceutical University

摘　　要：目的 比较由主动脉弓缩窄术(TAC)和异丙肾上腺素(ISO)构建的小鼠慢性心衰模型在超声心动图和病理上的变化差异。方法 小鼠适应性喂养1周后,随机分为假手术组、TAC手术组、正常对照组、ISO给药组,分别在TAC小鼠术后第0、2、4、6、8、10、12周、ISO给药后第0、14天,对小鼠进行超声心动图检测心脏功能指标。在12周通过qRT-PCR实验检测小鼠心脏组织炎性细胞因子和肥大相关标志物的表达变化,同时对模型小鼠的心脏组织进行HE染色,检测其心脏组织炎性浸润情况,Masson染色实验对模型小鼠的心脏纤维化程度进行评估。结果 与假手术组和正常对照组小鼠相比,TAC手术后12周和ISO给药组的小鼠心脏质量与体质量之比(HW/BW)和心脏质量与胫骨长度之比(HW/TL)都有明显上升,说明TAC术小鼠的心脏出现了明显的心肌肥大。超声心动图检测结果显示,模型组小鼠心脏舒张期和收缩期的室间隔厚度(IVSd和IVSs)明显下降,左心室内径(LVIDd和LVIDs)增加,左心室后壁厚度(LVPWd和LVPWs)呈轻度下降趋势,射血分数(EF%)、短轴缩短分数(FS%)、E/A峰比值降低。实时荧光定量PCR实验结果显示,TAC组、ISO给药组小鼠的心脏组织中IL-1β、IL-18、TNF-α等炎症因子均显著提高。HE和Masson染色结果显示,与假手术组和正常对照组的小鼠相比,模型组的小鼠心肌细胞排列障碍,细胞核增大、细胞肿胀,并伴有炎性浸润;同时,TAC小鼠的心脏组织中沉积了大量胶原纤维。结论 TAC手术方法和ISO给药方法均能导致小鼠出现从心肌肥厚、心肌肥大到心力衰竭的一系列病理性改变,但由于不同造模方法导致发病部位不一致,需要根据实验目的选择造模方法再进行实验研究。Objective To compare the changes of echocardiography and pathology in mouse models of chronic heart failure established by transverse aortic arch coarctation(TAC) and isoproterenol(ISO). Methods After one week of adaptive feeding, the mice were randomly divided into sham operation group, TAC operation group,normal control group, and ISO administration group. At 0, 2, 4, 6, 8, 10, 12 weeks after TAC operation, and at 0 and14 days after ISO administration, the mice were tested for cardiac function indexes by echocardiography. At the12th week, the expression of inflammatory cytokines and hypertrophy related markers in the heart tissue of the mice were detected by qRT-PCR experiment. Meantime, the heart tissue of the model mice was stained with HE to detect the inflammatory infiltration of the heart tissue. Masson staining was used to evaluate the degree of cardiac fibrosis of the model mice. Results Compared with the sham operation group and the normal control group, the ratio of heart mass to body mass(HW/BW) and the ratio of heart mass to tibia length(HW/TL) of the mice in the12 weeks after TAC operation and the ISO administration group increased significantly, indicating that the hearts of the mice in the TAC operation showed significant myocardial hypertrophy. Echocardiographic detection showed that the ventricular septal thickness(IVSd and IVSs) of the model group mouse heart in diastolic and systolic periods decreased significantly, the left ventricular inner diameter(LVIDd and LVIDs) increased, the left ventricular posterior wall thickness(LVPWd and LVPWs) showed a slight downward trend, and the ejection fraction(EF%), short axis shortening fraction(FS%), and E/A peak ratio decreased. qRT-PCR experiment showed that the inflammatory factors such as IL-1β, IL-18, and TNF-α in the heart tissue of TAC group and ISO group were significantly increased. HE and Masson staining showed that compared with the sham operation group and the normal control group, the arrangement of myocardial cells in the model group was

关 键 词：主动脉弓缩窄术 造模方法 异丙肾上腺素 心肌肥厚 慢性心力衰竭 

分 类 号：R-332[医药卫生]