Tong Fei, Zhang Hua
Cell Physiol Biochem. 2018;46(4):1493-1507. doi: 10.1159/000489192. Epub 2018 Apr 19.
BACKGROUND/AIMS: The purpose of this study was to investigate the effect of administering particulate matter (PM2.5) to the lungs on the sensitivity to myocardial ischemia/reperfusion injury (MI/RI) and the role of farnesoid-X-receptor (FXR)-induced autophagy in this process.
Male Sprague Dawley (SD) rats were subjected to 45 min of ischemia, and the lungs were exposed to 2.0 mg of PM2.5 in 0.3 mL of normal saline 5 min before reperfusion. After 24 h of reperfusion, the blood and myocardium were collected, and the myocardial infarct sizes, activities of serum creatine kinase (CK) and lactate dehydrogenase (LDH), and levels of serum high sensitivity C-reactive protein (hsCRP), interleukin-4 (IL-4), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), cardiac troponin T (cTnT), P-selectin and D-dimer were measured via biochemical analysis. Additionally, the myeloperoxidase (MDA) content and superoxide dismutase (SOD) activity were measured in myocardial tissues via biochemical analysis, and the levels of reactive oxygen species (ROS), autophagosomes, microtubule-associated protein 1 light chain 3 (LC-I and II), macrophage inflammatory protein-2 (MIP-2) and farnesoid-X-receptor (FXR) were determined in myocardial tissues via biochemical analysis, immunohistochemical and biochemical techniques and western blot. In addition, the myocardial infarct sizes, LC-I and II expressions were determined in myocardial tissues through FXR-/- and WT mice.
Levels of CK, LDH, hsCRP, IL-6, TNF-α, cTnT, P-selectin and D-dimer, MDA and infarct sizes were higher in I/R group than that in Sham group, and Levels of IL-4 and SOD were lower in I/R group than that in Sham group; ROS, autophagosomes, LC-3I, LC-3II, MIP-2 and FXR expressions were higher in I/R group than that in Sham group. Levels of CK, LDH, hsCRP, IL-6, TNF-α, cTnT, P-selectin and D-dimer, MDA and infarct sizes were higher in PM2.5 group than that in I/R group, and Levels of IL-4 and SOD were lower in PM2.5 group than that in I/R group; ROS, autophagosomes, LC-3I, LC-3II, MIP-2 and FXR expressions were higher in PM2.5 group than that in I/R group.
PM2.5 post-treatment exacerbated myocardial injury partly through upregulation of FXR to induce autophagy compared to MI/RI.
背景/目的：本研究旨在探讨肺部给予细颗粒物（PM2.5）对心肌缺血/再灌注损伤（MI/RI）敏感性的影响以及法尼酯X受体（FXR）诱导的自噬在此过程中的作用。
雄性Sprague Dawley（SD）大鼠经历45分钟的缺血，在再灌注前5分钟将肺部暴露于0.3 mL生理盐水中的2.0 mg PM2.5。再灌注24小时后，收集血液和心肌，通过生化分析测量心肌梗死面积、血清肌酸激酶（CK）和乳酸脱氢酶（LDH）活性以及血清高敏C反应蛋白（hsCRP）、白细胞介素-4（IL-4）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、心肌肌钙蛋白T（cTnT）、P-选择素和D-二聚体水平。此外，通过生化分析测量心肌组织中的髓过氧化物酶（MDA）含量和超氧化物歧化酶（SOD）活性，并通过生化分析、免疫组织化学和生化技术以及蛋白质印迹法测定心肌组织中的活性氧（ROS）、自噬体、微管相关蛋白1轻链3（LC-I和II）、巨噬细胞炎性蛋白-2（MIP-2）和法尼酯X受体（FXR）水平。另外，通过FXR-/-和野生型（WT）小鼠测定心肌组织中的心肌梗死面积、LC-I和II表达。
I/R组的CK、LDH、hsCRP、IL-6、TNF-α、cTnT、P-选择素和D-二聚体、MDA水平和梗死面积高于假手术组，I/R组的IL-4和SOD水平低于假手术组；I/R组的ROS、自噬体、LC-3I、LC-3II、MIP-2和FXR表达高于假手术组。PM2.5组的CK、LDH、hsCRP、IL-6、TNF-α、cTnT、P-选择素和D-二聚体、MDA水平和梗死面积高于I/R组，PM2.5组的IL-4和SOD水平低于I/R组；PM2.5组的ROS、自噬体、LC-3I、LC-3II、MIP-2和FXR表达高于I/R组。
与MI/RI相比，PM2.5后处理部分通过上调FXR诱导自噬加重心肌损伤。
