天津医药 ›› 2022, Vol. 50 ›› Issue (3): 253-258.doi: 10.11958/20212148

• 实验研究 • 上一篇    下一篇

格列本脲对糖尿病大鼠心房重构及心房颤动诱发的影响

霍宁,詹晓萍,周梦竹,张跃,梁雪,李广平,刘长乐   

  1. 天津市心血管病离子与分子机能重点实验室,天津心脏病学研究所,天津医科大学第二医院心脏科(邮编300211)
  • 收稿日期:2021-09-16 修回日期:2021-11-08 出版日期:2022-03-15 发布日期:2022-03-15
  • 基金资助:
    天津市应用基础与前沿技术研究计划(青年项目)(15JCQNJC10200,18JCQNJC82600)

Effects of glyburide on atrial remodeling and atrial fibrillation induction in diabetic rats

HUO Ning, ZHAN Xiaoping, ZHOU Mengzhu, ZHANG Yue, LIANG Xue, LI Guangping, LIU Changle   

  1. Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Tianjin Institute of Cardiology, Department of Cardiology, the Second Hospital of Tianjin Medical University, Tianjin 300211, China
  • Received:2021-09-16 Revised:2021-11-08 Published:2022-03-15 Online:2022-03-15

摘要: 目的 探究格列本脲(GLB)对糖尿病(DM)大鼠心房重构及心房颤动(AF)诱发的影响。方法 将48只SD大鼠按随机数字表法分为3组:对照组(Ctl组)、糖尿病组(DM组)和糖尿病+格列本脲组(GLB组),每组16只。采用链脲佐菌素法建立DM动物模型,GLB组大鼠每日灌胃服用GLB(10 mg/kg),动物于相同条件下饲喂6周,记录第6周空腹血糖及体质量。6周后进行心脏超声检查,记录舒张早期波峰值速度(E)、舒张晚期波峰值速度(A)、左心房内径、左心室射血分数、左心室短轴缩短率、E/A、肺动脉血流加速时间、平均肺动脉压、收缩与舒张期室间隔、左心室内径和左心室后壁厚度;无创血压计检测大鼠心率、收缩压和舒张压,计算平均动脉压。在体电生理实验检测大鼠房室文氏周长、窦房结恢复时间、有效不应期、AF诱发率;心外膜激活映射标测实验检测绝对不均匀指数与传导相对异质性、心外膜传导速度;Masson染色检测左心房间质纤维化,计算胶原容积分数(CVF)。结果 与DM组相比,GLB组心脏体质量比、心室体质量比降低,左心房内径减小(P<0.05)。DM组较Ctl组心外膜传导速度降低,传导相对异质性增加;与DM组相比,GLB组心外膜传导速度提高(P<0.05),传导相对异质性差异无统计学意义。GLB组较DM组R-R间期缩短,AF诱发率下降(P<0.05)。GLB组和DM组较Ctl组心房肌纤维化程度加重,CVF增大(P<0.05)。GLB组较DM组心房肌纤维化程度减轻,CVF减小(P<0.05)。结论 DM可促进大鼠心房组织纤维化,与AF发病有关,GLB可以通过延缓DM大鼠心肌组织纤维化进展来降低AF诱发率。

关键词: 心房颤动, 糖尿病, 格列本脲, 心房重构, 心肌纤维化

Abstract: Objective To investigate the effect of glyburide (GLB) on the induction of atrial remodeling and atrial fibrillation (AF) in diabetes mellitus (DM) rats. Methods Forty-eight SD rats were randomly divided into the three groups: the control group (Ctl group), the diabetes group (DM group) and the diabetes + GLB group (GLB group), with 16 rats in each group. The DM animal model was established by streptozotocin method, and the GLB group was given GLB (10 mg/kg) daily by gavage. The animals were fed under the same conditions for 6 weeks, and fasting blood glucose and body weight were recorded at the sixth weeks. The early diastolic peak velocity (E), late diastolic peak velocity (A), left atrial diameter, ejection fraction, left ventricular short axis shortening rate, E/A, pulmonary artery flow acceleration time, mean pulmonary artery pressure, systolic and diastolic ventricular septum, left ventricular diameter and left ventricular posterior wall thickness were measured by cardiac ultrasound 6 weeks later. Heart rate, systolic blood pressure, diastolic blood pressure and mean arterial blood pressure were measured. The atrioventricular, wenckebach cyclelength, recovery time of sinoatrial node, effective refractory period and AF induction rate of rats were measured by electrophysiological experiment. Epicardial activation mapping experiment was used to detect absolute inhomogeneity index, conduction heterogeneity and epicardial conduction velocity. Masson staining was used to detect left atrium fibrosis, and collagen volume fraction (CVF) was calculated. Results Compared with the DM group, lower heart body mass ratio and ventricular body mass ratio, lower left atrial inner diameter were found in the GLB group (P<0.05). Compared with the Ctl group, the epicardial conduction velocity was decreased and the relative conduction heterogeneity was increased in the DM group. Compared with the DM group, epicardial conduction velocity was increased in the GLB group (P<0.05), and there was no significant difference in conduction relative heterogeneity. Compared with the DM group, the GLB group had shorter R-R interval and lower AF induction rate (P<0.05). Compared with the Ctl group, the degree of atrial muscle fibrosis was worse and CVF increased in the GLB and the DM groups (P<0.05). Conclusion DM can promote atrial fibrosis in rats, which is correlated with the incidence of AF. GLB can reduce the induction rate of AF by delaying the progression of myocardial fibrosis in DM rats.

Key words: atrial fibrillation, diabetes mellitus, Glyburide, atrial remodeling, myocardial fibrosis