Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, 50200, Thailand.
Inflamm Res. 2022 Aug;71(7-8):861-872. doi: 10.1007/s00011-022-01590-2. Epub 2022 Jun 2.
Microglial hyperactivation and apoptosis were observed following myocardial infarction and ischemia reperfusion (I/R) injury. This study aimed to test the hypothesis that the apoptosis inhibitor, Z-VAD, attenuates microglial and astrocytic hyperactivation and brain inflammation in rats with cardiac I/R injury.
Rats were subjected to either sham or cardiac I/R operation (30 min-ischemia followed by 120-min reperfusion), rats in the cardiac I/R group were given either normal saline solution or Z-VAD at 3.3 mg/kg via intravenous injection 15 min prior to cardiac ischemia. Left ventricular ejection fraction (% LVEF) was determined during the cardiac I/R protocol. The brain tissues were removed and used to determine brain apoptosis, brain inflammation, microglial and astrocyte morphology.
Cardiac dysfunction was observed in rats with cardiac I/R injury as indicated by decreased %LVEF. In the brain, we found brain apoptosis, brain inflammation, microglia hyperactivation, and reactive astrogliosis occurred following cardiac I/R injury. Pretreatment with Z-VAD effectively increased %LVEF, reduced brain apoptosis, attenuated brain inflammation by decreasing IL-1β mRNA levels, suppressed microglial and astrocytic hyperactivation and proliferation after cardiac I/R injury.
Z-VAD exerts neuroprotective effects against cardiac I/R injury not only targeting apoptosis but also microglial and astrocyte activation.
在心肌梗死和缺血再灌注（I/R）损伤后观察到小胶质细胞的过度激活和凋亡。本研究旨在验证以下假设：凋亡抑制剂 Z-VAD 可减轻心肌 I/R 损伤大鼠的小胶质细胞和星形胶质细胞的过度激活和脑炎症。
大鼠接受假手术或心肌 I/R 手术（缺血 30 分钟，再灌注 120 分钟），心肌 I/R 组大鼠在缺血前 15 分钟静脉注射生理盐水或 Z-VAD（3.3mg/kg）。在心肌 I/R 方案期间确定左心室射血分数（%LVEF）。取出脑组织用于确定脑凋亡、脑炎症、小胶质细胞和星形胶质细胞形态。
心肌 I/R 损伤大鼠出现心功能障碍，表现为 %LVEF 降低。在大脑中，我们发现心肌 I/R 损伤后发生脑凋亡、脑炎症、小胶质细胞过度激活和反应性星形胶质细胞增生。Z-VAD 预处理有效增加 %LVEF，减少脑凋亡，通过降低 IL-1β mRNA 水平减轻脑炎症，抑制心肌 I/R 损伤后的小胶质细胞和星形胶质细胞过度激活和增殖。
Z-VAD 不仅针对细胞凋亡，而且针对小胶质细胞和星形胶质细胞的激活，对心肌 I/R 损伤具有神经保护作用。
