The New Nano-Resuscitation Solution (TPP-MR) Attenuated Myocardial Injury in Hemorrhagic Shock Rats by Inhibiting Ferroptosis.
Lei Tan, Han She, Yi Wang, Yuanlin Du, Jun Zhang, Yunxia Du, Yinyu Wu, Wei Chen, Bingqiang Huang, Duanyang Long, Xiaoyong Peng, Qinghui Li, Qingxiang Mao, Tao Li, Yi Hu
Author Information
Lei Tan: Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing, 400042, People's Republic of China.
Han She: Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing, 400042, People's Republic of China. ORCID
Yi Wang: Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing, 400042, People's Republic of China.
Yuanlin Du: Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing, 400042, People's Republic of China.
Jun Zhang: Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing, 400042, People's Republic of China.
Yunxia Du: Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing, 400042, People's Republic of China.
Yinyu Wu: Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing, 400042, People's Republic of China. ORCID
Wei Chen: Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing, 400042, People's Republic of China.
Bingqiang Huang: Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing, 400042, People's Republic of China.
Duanyang Long: Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing, 400042, People's Republic of China.
Xiaoyong Peng: State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Daping Hospital, Army Medical University, Chongqing, 400042, People's Republic of China.
Qinghui Li: State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Daping Hospital, Army Medical University, Chongqing, 400042, People's Republic of China.
Qingxiang Mao: Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing, 400042, People's Republic of China. ORCID
Tao Li: State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Daping Hospital, Army Medical University, Chongqing, 400042, People's Republic of China.
Yi Hu: Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing, 400042, People's Republic of China.
Background: Hemorrhagic shock was a leading cause of death worldwide, with myocardial injury being a primary affected organ. As commonly used solutions in fluid resuscitation, acetated Ringer's (AR) and Lactate Ringer's solution (LR) were far from perfect for their adverse reactions such as lactic acidosis and electrolyte imbalances. In previous studies, TPP@PAMAM-MR (TPP-MR), a novel nanocrystal resuscitation fluid has been found to protect against myocardial injury in septic rats. However, its role in myocardial injury in rats with hemorrhagic shock and underlying mechanism is unclear. Methods: The hemorrhagic shock rats and hypoxia-treated cardiomyocytes (H9C2) were utilized to investigate the impact of TPP-MR on cardiac function, mitochondrial function, and lipid peroxidation. The expressions of ferritin-related proteins glutathione peroxidase 4 (GPX4), Acyl CoA Synthase Long Chain Family Member 4 (ACSL4), and Cyclooxygenase-2(COX2) were analyzed through Western blotting to explore the mechanism of TPP-MR on hemorrhagic myocardial injury. Results: TPP-MR, a novel nanocrystalline resuscitation fluid, was synthesized using TPP@PAMAM@MA as a substitute for L-malic acid. We found that TPP-MR resuscitation significantly reduced myocardial injury reflected by enhancing cardiac output, elevating mean arterial pressure (MAP), and improving perfusion. Moreover, TPP-MR substantially prolonged hemorrhagic shock rats' survival time and survival rate. Further investigations indicated that TPP-MR improved the mitochondrial function of myocardial cells, mitigated the production of oxidative stress agents (ROS) and increased the glutathione (GSH) content. Additionally, TPP-MR inhibited the expression of the ferroptosis-associated GPX4 protein, ACSL4 and COX2, thereby enhancing the antioxidant capacity. Conclusion: The results showed that TPP-MR had a protective effect on myocardial injury in rats with hemorrhagic shock, and its mechanism might be related to improving the mitochondrial function of myocardial cells and inhibiting the process of ferroptosis.
