Department of Anesthesiology, Beijing Anzhen Hospital, Capital Medical University-Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, PR China.
Department of Anesthesiology, Beijing Anzhen Hospital, Capital Medical University-Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, PR China.
Eur J Pharmacol. 2017 Oct 5;812:48-56. doi: 10.1016/j.ejphar.2017.07.003. Epub 2017 Jul 4.
Pharmacological postconditioning offers a clinical perspective for all patients with ischemic heart disease. Penehyclidine hydrochloride (PHC) is a new type of anticholinergic drug. We previously reported that PHC preconditioning protects against I/R injury in rat hearts in vivo. Ischemic heart disease often occurs suddenly, so postconditioning is more significant than preconditioning. However, studies evaluating myocardial protective effects of PHC postconditioning are unavailable. We explored the effects and time-window of cardioprotection of PHC postconditioning in myocardial I/R injury. PHC was administered by intravenous at various times (t = -5, 0, 5, 10, 15, or 30min) after the onset of reperfusion in addition to I/R rat. We observed five different indicators including infarct size, inflammatory response, myocardial enzyme, oxidative stress, and Ca overload to quantify the effect of cardioprotection. Evans blue and TTC staining were used to measure myocardial infarct size. The expression of NF-κ B and IκB-α was analyzed using Western blot. ELISA was conducted to detect inflammatory and anti-inflammatory mediators. The Ca level was determined using assay kit. PHC postconditioning (from -5 to 10min after the onset of reperfusion) significantly reduced infarct size, downregulated NF-κ B expression, and decreased the release of inflammatory mediators, while significantly upregulating IκB-α expression and increasing the release of anti-inflammatory mediators. All PHC postconditioning groups significantly reduced Ca level. PHC postconditioning is cardioprotective over a larger time-window (from -5 to 10min after the onset of reperfusion). The probable mechanism is inhibition of NF-кB regulated inflammatory response pathway.
盐酸戊乙奎醚（PHC）是一种新型的抗胆碱能药物。我们之前的研究表明，PHC 预处理可在体内保护大鼠心脏免受 I/R 损伤。缺血性心脏病常突然发生，因此后处理比预处理更重要。然而，目前尚无评估 PHC 后处理对心肌保护作用的研究。我们探讨了 PHC 后处理在心肌 I/R 损伤中的心肌保护作用及其时间窗。在再灌注开始后，通过静脉给予 PHC（t = -5、0、5、10、15 或 30min），除了 I/R 大鼠。我们观察了五个不同的指标，包括梗塞面积、炎症反应、心肌酶、氧化应激和 Ca 过载，以量化心肌保护作用。使用 Evans 蓝和 TTC 染色测量心肌梗塞面积。通过 Western blot 分析 NF-κB 和 IκB-α 的表达。使用 ELISA 检测炎症和抗炎介质。使用试剂盒测定 Ca 水平。PHC 后处理（再灌注开始后-5 至 10min）显著减少梗塞面积，下调 NF-κB 表达，并减少炎症介质的释放，同时显著上调 IκB-α 表达并增加抗炎介质的释放。所有 PHC 后处理组均显著降低 Ca 水平。PHC 后处理具有更大的时间窗（再灌注开始后-5 至 10min）的心肌保护作用。可能的机制是抑制 NF-кB 调节的炎症反应途径。
