Lackner Ina, Weber Birte, Haffner-Luntzer Melanie, Hristova Simona, Gebhard Florian, Lam Charles, Morioka Kazuhito, Marcucio Ralph S, Miclau Theodore, Kalbitz Miriam
Department of Traumatology, Hand-, Plastic- and Reconstructive Surgery, University Medical Center Ulm, Ulm, Germany.
Orthopaedic Trauma Institute, Department of Orthopaedic Surgery, University of California, San Francisco, CA, USA.
J Orthop Translat. 2021 Feb 23;28:39-46. doi: 10.1016/j.jot.2020.12.003. eCollection 2021 May.
Trauma is the leading cause of death and disability worldwide, especially in the young population. Cardiac injuries are an independent predictor for a poor overall outcome after trauma. The aim of the present study was to analyze systemic inflammation as well as local cardiac inflammation after experimental limb-, neuro- and combined trauma in mice.
Male C57BL/6 mice received either a closed tibia fracture (Fx), isolated traumatic brain injury (TBI) or a combination of both (Fx + TBI). Control animals underwent sham procedure. After 6 and 24 h, systemic levels of inflammatory mediators were analyzed, respectively. Locally, cardiac inflammation and cardiac structural alterations were investigated in left ventricular tissue of mice 6 and 24 h after trauma.
Mice showed enhanced systemic inflammation after combined trauma, which was manifested by increased levels of KC, MCP-1 and G-CSF. Locally, mice exhibited increased expression of inflammatory cytokines (IL-1β, TNF) in heart tissue, which was probably mediated via toll-like receptor (TLR) signaling. Furthermore, mice demonstrated a redistribution of connexin 43 in cardiac tissue, which appeared predominantly after combined trauma. Besides inflammation and structural cardiac alterations, expression of glucose transporter 4 (GLUT4) mRNA was increased in the heart early after TBI and after combination of TBI and limb fracture, indicating a modification of energy metabolism. Early after combination of TBI and tibia fracture, nitrosative stress was increased, manifested by elevation of nitrotyrosine in cardiac tissue. Finally, mice showed a trend of increased systemic levels of cardiac troponin I and heart-fatty acid binding protein (HFABP) after combined trauma, which was associated with a significant decrease of troponin I and HFABP mRNA expression in cardiac tissue after TBI and combination of TBI and limb fracture.
Mice exhibited early cardiac alterations as well as alterations in cardiac glucose transporter expression, indicating a modification of energy metabolism, which might be linked to increased systemic- and local cardiac inflammation after limb-, neuro- and combined trauma. These cardiac alterations might predispose individuals for secondary cardiac damage after trauma that might compromise cardiac function after TBI and long bone fracture.
Injuries to the head and extremities frequently occur after severe trauma. In our study, we analyzed the effects of closed tibia fracture, isolated TBI, and the combination of both injuries with regard to the development of post-traumatic secondary cardiac injuries.
创伤是全球范围内导致死亡和残疾的主要原因，在年轻人群中尤为如此。心脏损伤是创伤后总体预后不良的独立预测因素。本研究的目的是分析小鼠实验性肢体创伤、神经创伤及联合创伤后的全身炎症反应以及局部心脏炎症反应。
雄性C57BL/6小鼠分别接受闭合性胫骨骨折（Fx）、单纯创伤性脑损伤（TBI）或两者联合损伤（Fx + TBI）。对照动物接受假手术。分别在6小时和24小时后分析炎症介质的全身水平。在创伤后6小时和24小时，对小鼠左心室组织进行局部心脏炎症和心脏结构改变的研究。
联合创伤后小鼠全身炎症反应增强，表现为KC、MCP - 1和G - CSF水平升高。在局部，小鼠心脏组织中炎症细胞因子（IL - 1β、TNF）表达增加，这可能是通过Toll样受体（TLR）信号传导介导的。此外，小鼠心脏组织中连接蛋白43出现重新分布，主要在联合创伤后出现。除了炎症和心脏结构改变外，TBI后以及TBI与肢体骨折联合后早期，心脏中葡萄糖转运蛋白4（GLUT4）mRNA表达增加，表明能量代谢发生改变。TBI与胫骨骨折联合后早期，心脏组织中硝基酪氨酸水平升高，表明亚硝化应激增加。最后，联合创伤后小鼠全身心肌肌钙蛋白I和心脏脂肪酸结合蛋白（HFABP）水平有升高趋势，这与TBI以及TBI与肢体骨折联合后心脏组织中肌钙蛋白I和HFABP mRNA表达显著降低有关。
小鼠表现出早期心脏改变以及心脏葡萄糖转运蛋白表达改变，表明能量代谢发生改变，这可能与肢体创伤、神经创伤及联合创伤后全身和局部心脏炎症增加有关。这些心脏改变可能使个体在创伤后易发生继发性心脏损伤，进而可能损害TBI和长骨骨折后的心脏功能。
严重创伤后头部和四肢损伤很常见。在我们的研究中，我们分析了闭合性胫骨骨折、单纯TBI以及两种损伤联合对创伤后继发性心脏损伤发生发展的影响。
