Wang Minjie, Hua Tianfeng, Zhang Yijun, Huang Qihui, Shi Wei, Chu Yuqian, Hu Yan, Pan Sinong, Ling Bingrui, Tang Wanchun, Yang Min
The Second Department of Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China; Laboratory of Cardiopulmonary Resuscitation and Critical Care, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.
Eur J Pharmacol. 2025 Feb 5;988:177212. doi: 10.1016/j.ejphar.2024.177212. Epub 2024 Dec 18.
Canagliflozin can reduce the risk of cardiovascular disease in patients except for its targeted antidiabetic effects. However, it remains unknown whether canagliflozin alleviates the post-resuscitation myocardial dysfunction (PRMD) in type 2 diabetes mellitus.
To explore the effects and potential mechanisms of canagliflozin on myocardial function after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) in a type 2 diabetic rat model.
Twenty-four type 2 diabetic rats were randomized into four groups: (1) sham + canagliflozin, (2) sham + placebo, (3) CPR + placebo, and (4) CPR + canagliflozin. Except for the sham + canagliflozin and placebo groups, both the CPR + placebo and canagliflozin groups underwent 8 min of CPR after the induction of ventricular fibrillation for 6 min. Myocardial function and hemodynamics were assessed at baseline and within 6 h after autonomous circulation (ROSC) return. Left ventricular tissues were sampled to determine the expressions of relevant proteins in the NLRP3 inflammasome pathway.
The results demonstrated that the mean arterial pressure (MAP) was significantly improved in the CPR + canagliflozin group after ROSC compared with the CPR + placebo group (p < 0.05). Meanwhile, both ejection fraction (EF) and fraction shortening (FS) were dramatically increased in the CPR + canagliflozin group when compared with the CPR + placebo group at 2h, 4h, and 6h after ROSC (p < 0.05). In addition, the levels of NT-proBNP, cTn-I, and NLRP3 inflammatory inflammasome-associated proteins were significantly decreased in the CPR + canagliflozin group compared with the CPR + placebo group.
In type 2 diabetic rats, pretreatment of canagliflozin alleviates PRMD. The potential mechanisms may include inhibition of the NLRP3/caspase-1 signaling pathway.
卡格列净除了具有靶向降糖作用外，还可降低患者心血管疾病风险。然而，卡格列净是否能减轻2型糖尿病患者复苏后心肌功能障碍（PRMD）仍不清楚。
探讨卡格列净对2型糖尿病大鼠模型心脏骤停（CA）和心肺复苏（CPR）后心肌功能的影响及潜在机制。
将24只2型糖尿病大鼠随机分为四组：（1）假手术+卡格列净组，（2）假手术+安慰剂组，（3）心肺复苏+安慰剂组，（4）心肺复苏+卡格列净组。除假手术+卡格列净组和安慰剂组外，心肺复苏+安慰剂组和卡格列净组在诱导室颤6分钟后均进行8分钟的心肺复苏。在基线和自主循环恢复（ROSC）后6小时内评估心肌功能和血流动力学。采集左心室组织以测定NLRP3炎性小体途径中相关蛋白的表达。
结果表明，与心肺复苏+安慰剂组相比，心肺复苏+卡格列净组在ROSC后平均动脉压（MAP）显著改善（p<0.05）。同时，与心肺复苏+安慰剂组相比，心肺复苏+卡格列净组在ROSC后2小时、4小时和6小时的射血分数（EF）和缩短分数（FS）均显著增加（p<0.05）。此外，与心肺复苏+安慰剂组相比，心肺复苏+卡格列净组中NT-proBNP、cTn-I和NLRP3炎性炎性小体相关蛋白水平显著降低。
在2型糖尿病大鼠中，卡格列净预处理可减轻PRMD。潜在机制可能包括抑制NLRP3/caspase-1信号通路。
