实验动物与比较医学 ›› 2024, Vol. 44 ›› Issue (6): 605-612.DOI: 10.12300/j.issn.1674-5817.2024.078

• 人类疾病动物模型 • 上一篇    下一篇

应用Triacsin C构建新型高血糖肥胖小鼠心功能减退模型

赵小娜1(), 王鹏2, 叶茂青3, 曲新凯1()()   

  1. 1.复旦大学附属华东医院心血管内科, 上海 200040
    2.复旦大学附属中山医院心血管内科, 上海 200032
    3.上海市老年医学临床重点实验室, 上海 200040
  • 收稿日期:2024-05-31 修回日期:2024-10-21 出版日期:2025-01-04 发布日期:2024-12-25
  • 通讯作者: 曲新凯(1972—),男,博士,教授,博士生导师,主任医师,研究方向:老年冠心病的诊疗。E-mail: qxkchest@126.com。ORCID: 0000-0002-5000-6721
  • 作者简介:赵小娜(1989—),女,硕士研究生,研究方向:老年冠心病的诊疗。E-mail: zxncardiac1224@163.com
  • 基金资助:
    复旦大学附属华东医院院级课题“SCFA通过抑制IL-1β-NLRP3炎症小体产生减轻动脉粥样硬化”(H1297);华东医院重点学科建设计划“临床医学研究中心-心血管内科”(LCZX2205)

Establishment of a New Hyperglycemic Obesity Cardiac Dysfunction Mouse Model with Triacsin C

ZHAO Xiaona1(), WANG Peng2, YE Maoqing3, QU Xinkai1()()   

  1. 1.Department of Cardiology, Huadong Hospital, Fudan University, Shanghai 200040, China
    2.Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
    3.Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai 200040, China
  • Received:2024-05-31 Revised:2024-10-21 Published:2024-12-25 Online:2025-01-04
  • Contact: QU Xinkai (ORCID: 0000-0002-5000-6721), E-mail: qxkchest@126.com

摘要:

目的 应用长链酰基辅酶A合成酶1(acyl-CoA synthetase long-chain family member 1,ACSL1)抑制剂Triacsin C联合高脂饮食建立新的高血糖肥胖小鼠心功能减退模型,以模拟肥胖相关2型糖尿病患者脂肪组织和心功能的变化。 方法 将20只SPF级雄性C57BL/6J小鼠随机分为2组:Con组(对照组,腹腔注射柠檬酸-柠檬酸钠缓冲液)和TC组(实验组,腹腔注射Triacsin C)。连续注射4周后,2组小鼠均给予高脂饲料喂养,自实验开始每8周监测小鼠体重及糖耐量。以空腹血糖>8 mmol/L或餐后2 h血糖>15 mmol/L视为造模成功。观测2组小鼠左心室舒张末期内径(left ventricular end-diastolic diameter,LVEDD)、左心室收缩末期内径(left ventricular end-systolic diameter,LVESD)、舒张末期室间隔厚度(end-diastolic interventricular septal thickness,EDIVS)、左心室射血分数(left ventricular ejection fraction,LVEF)和左心室短轴缩短分数(left ventricular short-axis fractional shortening,FS)等心功能指标的变化。HE染色后观测小鼠附睾白色脂肪组织(white adipose tissue,WAT)及背部棕色脂肪组织(brown adipose tissue,BAT)形态和面积的变化;采用免疫荧光法分析棕色脂肪组织血管内皮标志蛋白CD31和棕色脂肪组织标志蛋白UCP1的变化;采用蛋白质印迹法检测小鼠心肌组织中ACSL1表达的变化。 结果 Con组和TC组小鼠空腹血糖分别为(8.14±1.43)mmol/L和 (8.18±0.85)mmol/L(P>0.05),餐后2 h血糖浓度分别为(19.8±4.01)mmol/L和 (22.60±3.97)mmol/L(P<0.05),表明本研究中两组糖尿病小鼠模型均造模成功。与Con组相比,TC组小鼠葡萄糖耐量较差,LVEDD、LVEF和FS下降明显(P<0.05),WAT及BAT面积明显增大(P<0.05),CD31、UCP1的表达量明显减少(P<0.05),心肌组织ACSL1表达明显减少(P<0.05)。 结论 Triacsin C联合高脂饮食制备新型高血糖肥胖小鼠心功能减退模型是可行的,较单纯高脂饮食诱导2型糖尿病模型出现明显的棕色脂肪组织白色化、胰岛素抵抗及心功能减退现象。

关键词: 动物模型, 长链脂酰辅酶A合成酶1, 棕色脂肪组织, 心功能减退, 小鼠

Abstract:

Objective This study aims to establish a novel hyperglycemic obesity mouse model by utilizing Triacsin C, an inhibitor of acyl-CoA synthetase long-chain family member 1 (ACSL1), combined with a high-fat diet, to simulate the changes in adipose tissue and cardiac function observed in patients with obesity-related type 2 diabetes. Methods Twenty adult SPF-grade male C57BL/6J mice were randomly divided into two groups: the Control group (injected intraperitoneally with citric acid-sodium citrate buffer, Con group) and the TC group (injected intraperitoneally with Triacsin C, TC group). After four consecutive weeks of intraperitoneal injections, both groups were fed high-fat diets. Body weight and glucose tolerance of the mice were assessed every eight weeks. The models were considered successful if fasting blood glucose exceeded 8 mmol/L or blood glucose was above 15 mmol/L two hours after glucose injection. Cardiac function, including ventricular end-diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), end-diastolic interventricular septal thickness (EDIVS), left ventricular ejection fraction (LVEF), and left ventricular short-axis fractional shortening (FS), was measured by echocardiography. HE staining was used to detect the changes in epididymal white adipose tissue (WAT) and brown adipose tissue (BAT). Immunofluorescence technology was used to analyze changes in CD31 and UCP1 in BAT. ACSL1 expression in myocardial tissue was tested by Western blotting. Results The fasting blood glucose levels were (8.14±1.43) mmol/L in the Con group and (8.18±0.85) mmol/L in the TC group (P>0.05) , and the 2-hour postprandial blood glucose levels were (19.8±4.01) mmol/L in the Con group and (22.60±3.97) mmol/L in the TC group (P<0.05). This indicated that both groups of diabetic mouse models were successfully established. Compared to the Con group, the TC group showed poor glucose tolerance; significant decreases in LVEDD, LVEF and FS (P<0.05); significant increases in WAT and BAT areas (P<0.05); significant decreases in CD31 and UCP1 expression (P<0.05); and a significant decrease in the expression of ACSL1 in myocardial tissues (P<0.05). Conclusion Compared with the high-fat diet-induced type 2 diabetes model, the new hyperglycemic obesity and cardiac dysfunction mouse model, created by the combination of Triacsin C and a high-fat diet, is feasible and allows for easier observation of brown adipose tissue whitening, insulin resistance and cardiac dysfunction.

Key words: Animal model, Acyl-CoA synthetase long-chain family member 1, Brown adipose tissue, Cardiac dysfunction, Mice

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