Vasodilator Stress Echocardiography in the Assessment of Early Coronary Microvascular Function in Type II Diabetic Mice
Vasodilator Stress Echocardiography in the Assessment of Early Coronary Microvascular Function in Type II Diabetic Mice
复制标题
血管舒张负荷超声心动图评估 II 型糖尿病小鼠早期冠状动脉微血管功能
DOI：
10.1166/jmihi.2018.2439
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发表时间：
2018-08
影响因子：
--
通讯作者：
Xie Jinjie
中科院分区：
文献类型：
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作者：
Li Rongjuan;Sun Zhonghua;Wang Yueli;Liu Guowen;Pu Lihong;Leng Zhaoting;Yang Ya;Xie Jinjie
瘦素受体缺乏的db/db小鼠是一种完善的II型糖尿病动物模型，用于研究糖尿病性心肌病。糖尿病引起冠状动脉微血管循环的功能和结构异常，在糖尿病性心肌病的发生发展中起重要作用。本研究的目的是利用血管扩张剂应激超声心动图评估糖尿病db/db小鼠体内冠状动脉微血管功能，以研究II型糖尿病模型冠状动脉微血管循环的早期变化。材料与方法分别于8、12、16周龄对C57BL/6J型糖尿病雄性小鼠和同龄对照小鼠进行超声心动图检查。小鼠用2%异氟醚与100%氧气汽化麻醉。在胸骨旁左室短轴位中乳头水平，用m型超声心动图测定舒张末期和收缩末期左室直径、室间隔厚度和后壁厚度、射血分数、缩短分数。异氟烷降至1%以测量改良胸骨旁左心室长轴位下左前降支基线冠状动脉流量，然后增加至3%以测量最大冠状动脉流量。冠状动脉血流速度储备（CFVR）计算为高异氟烷浓度（3%）时达到的最高血流时的峰值舒张速度（PDV）与最低异氟烷浓度（1%）时达到的最低基线血流时的峰值舒张速度（PDV）之比：CFVR=冠状动脉充血流速(PDVh)/冠状动脉基础流速（PDVb）。结果8、12、16周龄时，db/db与年龄匹配的对照组在室间隔厚度、后壁厚度、舒张末期和收缩期左室直径、射血分数和缩短分数方面均无显著差异（P < 0.05）。8周龄时，两组左前降支PDVb、PDVh、CFVR差异无统计学意义。12周龄时，db/db小鼠的CFVR低于对照组（P < 0.01）。16周龄时，dbdb小鼠PDVh和CFVR显著降低（p0.01），但PDVb保持不变。CFVR与db/db、C57BL/6小鼠血糖水平呈显著负相关（r = -0.612, P < 0.01）。结论db/db小鼠从12周龄开始出现CFVR下降，提示冠状动脉微血管功能受损。高血糖的存在可能是冠状动脉血管扩张剂反应受损的一个重要因素。
BackgroundThe leptin receptor-deficient db/db mouse is a well-established type II diabetes animal model used to investigate diabetic cardiomyopathy. Diabetes mellitus induces functional and structural abnormalities of the coronary microvascular circulation, which can play a role in the development of diabetic cardiomyopathy. The objective of this study was to use vasodilator stress echocardiography to assess coronary microvascular function in vivo with diabetic db/db mice in order to study early changes of the coronary microvascular circulation in type II diabetes model.Materials and methodMale diabetic db/db mice and age-matched control mice from C57BL/6J strain at 8, 12 and 16 weeks of age were subjected to echocardiography. Mice were anesthetized with 2% isoflurane vaporized with 100% oxygen. At the mid-papillary level in the parasternal left ventricular short-axis view, end diastolic and systolic left ventricular diameter, interventricular septal thickness and posterior wall thicknesses, ejection fraction, fractional shortening were determined by M-mode echocardiography. Isoflurane was reduced to 1% to measure baseline left anterior descending coronary artery flow under a modified parasternal left ventricle long-axis view, and then increased to 3% to measure maximal coronary flow. Coronary flow velocity reserve (CFVR) was calculated as the ratio of peak diastolic velocity (PDV) at the highest flow attained during the high level of isoflurane (3%) to PDV at the minimum baseline flow obtained at the lowest level of isoflurane (1%): CFVR= Hyperemic coronary flow velocity (PDVh)/Basal coronary flow velocity (PDVb).ResultsThere was no significant difference in interventricular septal thickness, posterior wall thicknesses, end diastolic and systolic left ventricular diameter, ejection fraction and fractional shortening between db/db and age-matched control mice at 8, 12 or 16 weeks of age (P > 0.05). At 8 weeks of age, there was no significant difference in PDVb, PDVh and CFVR of the left anterior descending artery. At 12 weeks of age, CFVR in db/db mice was lower than in control mice (P 0.01). At 16 weeks of age, PDVh and CFVR was significantly decreased in dbdb mice (P 0.01), although PDVb remained unchanged. A significant negative correlation was noted between CFVR and the blood glucose level in db/db and C57BL/6 mice (r = –0.612, P 0.01).ConclusionThe present study confirmed that db/db mice showed the decreased CFVR from the age of 12 weeks, suggesting the impairment of coronary microvascular function. The presence of hyperglycemia may be a significant contributor to the development of impaired coronary vasodilator response.