Li Lei, Peng Xin, Guo Lichun, Zhao Yuhan, Cheng Qinghong
Department of Critical Care Medicine, Medical School of Shihezi University Shihezi 832003, P. R. China.
Department of Critical Care Medicine, First Affiliated Hospital, School of Medicine, Shihezi University Shihezi 832008, Xinjiang, P. R. China.
Int J Clin Exp Pathol. 2020 May 1;13(5):964-971. eCollection 2020.
Endoplasmic reticulum stress (ERS), arising from the loss of dynamic balance in endoplasmic reticulum function under stress and inflammation, has been implicated in the progression of sepsis. Multiple organ failure caused by sepsis still has a high mortality rate, of which the heart is one of the more damaged organs. In this research, a rat model of sepsis was set up by cecal ligation and puncture (CLP); serum myocardial enzyme levels were measured using an automated biochemical analyzer, inflammatory cytokine levels were measured by ELISA kit, and cardiac histology and cardiomyocyte apoptosis were measured by hematoxylin and eosin (H&E) staining and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay to assess the extent of myocardial damage. Western blot was used to detect expression of related proteins. The results showed that serum myocardial enzymes and pro-inflammatory factors were elevated in septic rats, and the increase was most significant in the CLP 24 h group. At the same time, the myocardium of septic rats had a histopathologic abnormality. After CLP, levels of endoplasmic reticulum stress related protein were upregulated. After 12 and 24 hours, the density of apoptotic cells in the myocardium of CLP-treated rats increased significantly, and the expression of apoptosis-related proteins changed significantly. This suggests that the unfolded protein response occurs during sepsis and causes damage to the heart muscle. Endoplasmic reticulum stress-mediated apoptotic signaling pathway is one of the causes of cardiac injury caused by sepsis, and may be a key to clinical prevention of cardiac dysfunction caused by sepsis.
内质网应激（ERS）源于应激和炎症状态下内质网功能动态平衡的丧失，与脓毒症的进展有关。脓毒症所致的多器官功能衰竭死亡率仍居高不下，其中心脏是受损较为严重的器官之一。本研究通过盲肠结扎穿刺（CLP）建立脓毒症大鼠模型；采用自动生化分析仪检测血清心肌酶水平，用ELISA试剂盒检测炎症细胞因子水平，通过苏木精-伊红（H&E）染色和末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）法检测心脏组织学和心肌细胞凋亡情况，以评估心肌损伤程度。采用蛋白质免疫印迹法检测相关蛋白表达。结果显示，脓毒症大鼠血清心肌酶和促炎因子升高，在CLP 24 h组升高最为显著。同时，脓毒症大鼠心肌存在组织病理学异常。CLP后，内质网应激相关蛋白水平上调。12 h和24 h后，CLP处理大鼠心肌凋亡细胞密度显著增加，凋亡相关蛋白表达发生明显变化。这表明脓毒症期间发生了未折叠蛋白反应并导致心肌损伤。内质网应激介导的凋亡信号通路是脓毒症所致心脏损伤的原因之一，可能是临床预防脓毒症所致心脏功能障碍的关键。
