Sodium-Glucose Co-Transporter 2 Inhibition With Empagliflozin Improves Cardiac Function After Cardiac Arrest in Rats by Enhancing Mitochondrial Energy Metabolism.
Sodium-Glucose Co-Transporter 2 Inhibition With Empagliflozin Improves Cardiac Function After Cardiac Arrest in Rats by Enhancing Mitochondrial Energy Metabolism.
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硫酸葡萄糖共转运蛋白2用雌激素抑制通过增强线粒体能量代谢，改善大鼠心脏骤停后心脏功能。
DOI：
10.3389/fphar.2021.758080
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发表时间：
2021
影响因子：
5.6
通讯作者：
Wang P
中科院分区：
文献类型：
--
作者：
Tan Y;Yu K;Liang L;Liu Y;Song F;Ge Q;Fang X;Yu T;Huang Z;Jiang L;Wang P
Empagliflozin 是一种新开发的抗糖尿病药物，通过高度选择性抑制钠-葡萄糖协同转运蛋白 2 来降低高血糖。高血糖常见于心脏骤停 (CA) 后的患者，并且与较差的预后相关。在本研究中，我们研究了恩格列净对 CA 后心肌功能障碍大鼠心功能的影响。非糖尿病雄性 Sprague-Dawley 大鼠接受心室颤动以诱导 CA，即假手术。大鼠在恢复自主循环后 10 分钟通过腹腔注射接受 10 mg/kg 的恩格列净或载体。通过超声心动图、组织学分析、心肌损伤分子标记、氧化应激、线粒体超微结构完整性和代谢来评估心脏功能。我们发现恩格列净不影响心率和血压，但与媒介物治疗组相比，恩格列净治疗组的左心室功能和生存时间显着更高。 Empagliflozin 还可以降低 CA 后的心肌纤维化、血清心肌肌钙蛋白 I 水平和心肌氧化应激。此外，恩格列净可维持心肌线粒体的结构完整性并增加 CA 后的线粒体活性。此外，恩格列净可增加循环酮和心肌酮水平以及心脏 β-羟基丁酸脱氢酶 1 蛋白表达。总之，这些代谢变化与心脏能量代谢的增加有关。因此，恩格列净对 CA 后急性心肌功能障碍的非糖尿病大鼠的心脏功能有有利的影响，与降低血糖水平和增加酮体氧化代谢有关。我们的数据表明，恩格列净可能有益于 CA 后心肌功能障碍的患者。
Empagliflozin is a newly developed antidiabetic drug to reduce hyperglycaemia by highly selective inhibition of sodium–glucose co-transporter 2. Hyperglycaemia is commonly seen in patients after cardiac arrest (CA) and is associated with worse outcomes. In this study, we examined the effects of empagliflozin on cardiac function in rats with myocardial dysfunction after CA. Non-diabetic male Sprague–Dawley rats underwent ventricular fibrillation to induce CA, or sham surgery. Rats received 10 mg/kg of empagliflozin or vehicle at 10 min after return of spontaneous circulation by intraperitoneal injection. Cardiac function was assessed by echocardiography, histological analysis, molecular markers of myocardial injury, oxidative stress, mitochondrial ultrastructural integrity and metabolism. We found that empagliflozin did not influence heart rate and blood pressure, but left ventricular function and survival time were significantly higher in the empagliflozin treated group compared to the group treated with vehicle. Empagliflozin also reduced myocardial fibrosis, serum cardiac troponin I levels and myocardial oxidative stress after CA. Moreover, empagliflozin maintained the structural integrity of myocardial mitochondria and increased mitochondrial activity after CA. In addition, empagliflozin increased circulating and myocardial ketone levels as well as heart β-hydroxy butyrate dehydrogenase 1 protein expression. Together, these metabolic changes were associated with an increase in cardiac energy metabolism. Therefore, empagliflozin favorably affected cardiac function in non-diabetic rats with acute myocardial dysfunction after CA, associated with reducing glucose levels and increasing ketone body oxidized metabolism. Our data suggest that empagliflozin might benefit patients with myocardial dysfunction after CA.
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影响因子：
11.1
作者：
Krahmer, Natalie;Farese, Robert V., Jr.;Walther, Tobias C.
通讯作者：
Walther, Tobias C.
影响因子：
37.8
作者：
Fishman GI;Chugh SS;Dimarco JP;Albert CM;Anderson ME;Bonow RO;Buxton AE;Chen PS;Estes M;Jouven X;Kwong R;Lathrop DA;Mascette AM;Nerbonne JM;O'Rourke B;Page RL;Roden DM;Rosenbaum DS;Sotoodehnia N;Trayanova NA;Zheng ZJ
通讯作者：
Zheng ZJ
影响因子：
4.4
作者：
Achanta, Lavanya B.;Rae, Caroline D.
通讯作者：
Rae, Caroline D.
影响因子：
8.8
作者：
Ayoub IM;Radhakrishnan J;Gazmuri RJ
通讯作者：
Gazmuri RJ
影响因子：
5.8
作者：
Ettleson, Matthew D.;Arguello, Vanessa;Molitch, Mark E.
通讯作者：
Molitch, Mark E.