Abstract:[Abstract]Objective: To determine whether dynaminrelated protein 1(DRP1) plays a role in sepsisinduced conversion of cardiomyocytes into a proinflammatory phenotype. Methods: Rat model of sepsis was induced by intraperitoneal(i.p.) injection of fecal material (180 mg/mL) at a dose of 3 g/kg body weight. Rat received normal saline(NS) served as control(sham). Rats were treated by Mdivi1 (25 mg/kg, i.p.) for 1 h before rat sepsis models were developed. Six hours after the induction of sepsis, rat plasma was isolated and hearts were harvested for myocardial myeloperoxidase(MPO) and neutrophil infiltration assay. Isolated rat cardiomyocytes were challenged with either septic plasma (from septic rat), or sham plasma(from sham rat), DRP1 activation was evaluated with DRP1 serine 637(S637) dephosphorylation and mitochondria translocation. Proinflammatory phenotype of cardiomyocytes was determined by measuring chemokine (LIX and KC) expression. Results: Rat with sepsis incurred increased myocardial MPO activity and myocardial neutrophil accumulation. Treatment of the septic rat with Mdivi-1(25 mg/kg) attenuated the sepsisinduced increase in myocardial MPO activity and myocardial neutrophil accumulation. Challenge of cardiomyocytes with septic plasma activate DRP1 and promote DRP1 mitochondria translocation,and result in conversion of cardiomyocytes into a proinflammatory phenotype as indicated by increase in LIX and KC expression. Mdivi1(10 μmol/L) pretreatment could attenuate the increase in LIX and KC production in cardiomyocytes with septic plasma. Conclusion: The activation of DRP1 plays a pivotal role in conversion of cardiomyocytes into proinflammatory phenotype in sepsis.
姜伟鹏,陶艾彬,安静霞,王好,张国辉,芮涛. 动力相关蛋白1迁移在脓毒症心肌细胞炎症反应中的作用[J]. 江苏大学学报:医学版, 2016, 26(02): 137-142.
JIANG Wei-peng, Tao Ai-bin, AN Jing-xia, WANG Hao, ZHANG Guo-hui, RUI Tao. Role of dynamin-related protein 1 translocation in sepsis-induced cardiomyocytes inflammatory response. Journal of Jiangsu University(Medicine Edition), 2016, 26(02): 137-142.
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