Gholami Sanaz, Mokhtari Behnaz, Badalzadeh Reza
Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Islamic Republic of Iran.
Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Islamic Republic of Iran.
J Diabetes Metab Disord. 2022 Mar 31;21(1):707-716. doi: 10.1007/s40200-022-01034-y. eCollection 2022 Jun.
Prevention of lethal ventricular arrhythmias induced by myocardial ischemia/reperfusion (I/R) in diabetic patients is the major goal of cardioprotective strategies. Here, we aimed to examine the anti-arrhythmic effect of ischemic postconditioning (IPostC) and alpha-lipoic acid (ALA) in myocardial I/R injury of type-II diabetic rats, focusing on the involvement of connexin-43 and nitric oxide (NO) in this context.
Diabetes (duration of 12 weeks) was induced by high-fat diet and low dose of streptozotocin in thirty male Wistar rats (12 weeks old, 200-250 g). After mounting the hearts on the Langendorff apparatus, I/R was induced by the ligation of left anterior descending coronary artery for 35 min, and reperfusion for 60 min. ALA (100 mg/kg/day) was administered orally in diabetic rats for five weeks before I/R. IPostC was applied immediately at early reperfusion. The arrhythmias were evaluated according to the Lambeth convention. Connexin-43 expression and NO levels were assessed by western blotting and Griess calorimetric method, respectively.
IPostC could not significantly decrease the number, duration, and incidence of premature ventricular contraction, ventricular tachycardia, and ventricular fibrillation, also the severity of arrhythmias in diabetic hearts. However, IPostC in combination with ALA-preconditioning significantly decreased the above mentioned parameters compared with untreated or monotherapies-received diabetic rats (P < 0.05 to P < 0.001). Furthermore, this combination therapy significantly increased connexin-43 expression and NO levels, compared with untreated diabetic rats (P < 0.01).
Preconditioning with ALA restored anti-arrhythmic effect of IPostC in diabetic hearts. Increased connexin-43 expression and NO levels may be the key players in this cardioprotection.
预防糖尿病患者心肌缺血/再灌注（I/R）诱发的致死性室性心律失常是心脏保护策略的主要目标。在此，我们旨在研究缺血后处理（IPostC）和α-硫辛酸（ALA）对II型糖尿病大鼠心肌I/R损伤的抗心律失常作用，重点关注连接蛋白43和一氧化氮（NO）在此过程中的作用。
采用高脂饮食和低剂量链脲佐菌素诱导30只雄性Wistar大鼠（12周龄，体重200 - 250克）患糖尿病（病程12周）。将心脏安装在Langendorff装置上后，通过结扎左冠状动脉前降支35分钟，然后再灌注60分钟诱导I/R。在I/R前，糖尿病大鼠口服ALA（100毫克/千克/天），持续五周。在再灌注早期立即进行IPostC。根据兰贝斯会议标准评估心律失常。分别通过蛋白质印迹法和Griess比色法评估连接蛋白43的表达和NO水平。
IPostC不能显著降低糖尿病心脏中室性早搏、室性心动过速和室颤的数量、持续时间和发生率，以及心律失常的严重程度。然而，与未治疗或接受单一疗法的糖尿病大鼠相比，IPostC联合ALA预处理显著降低了上述参数（P < 0.05至P < 0.001）。此外，与未治疗的糖尿病大鼠相比，这种联合治疗显著增加了连接蛋白43的表达和NO水平（P < 0.01）。
ALA预处理恢复了IPostC对糖尿病心脏的抗心律失常作用。连接蛋白43表达增加和NO水平升高可能是这种心脏保护作用的关键因素。
