Department of Anesthesiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
J Surg Res. 2011 Aug;169(2):267-76. doi: 10.1016/j.jss.2009.12.017. Epub 2010 Jan 14.
Studies have documented the beneficial roles of δ opioid receptor (OR) agonist for hemorrhagic shock. However, the myocardial protection roles and the mechanisms of hemodynamic stability during resuscitation of δ-OR agonist have not been explored. This study was designed to investigate myocardial protective effects and the mechanisms of high selective δ(1) and δ(2)-OR agonists during resuscitation of acute hemorrhagic shock.
Forty-eight adult male SD rats were adopted 60-min hemorrhagic shock through removing 30% (5 mL) of the total blood volume, and followed by 2-h resuscitation with shed blood and L-lactated Ringer's solution. At the end of shock and prior to resuscitation, NS, δ(1)-OR agonist TAN-67 (10 mg/kg) and antagonist BNTX (3 mg/kg), and BNTX+TAN-67, DMSO, δ(2)-OR agonist Deltorphin II (1 mg/kg) and antagonist NTB (2 mg/kg), and NTB+Deltorphin II in 0.5 mL were administrated. Left ventricular function parameters were measured during the whole experimental period. Myocardial mitochondria were isolated to determine opening of mitochondrial permeability transition pore (mPTP). Morphologic changes in myocardium and mitochondria were observed by electron microscope.
The hemodynamic indexes in group TAN-67 and group Deltorphin II were higher than control group at each time point during resuscitation, respectively (P<0.05). TAN-67 and Deltorphin II decrease but their antagonists BNTX and NTB increase the opening of mPTP (P<0.05). Myocardial and mitochondrial damage were attenuated in group TAN-67 and group Deltorphin II.
δ(1)-OR agonist TAN-67 and δ(2)-OR agonist Deltorphin II protect the heart by targeting the mPTP in rats with acute hemorrhagic shock.
已有研究证实 δ 阿片受体（OR）激动剂对失血性休克有益。然而，δ-OR 激动剂在复苏过程中对血流动力学稳定的心肌保护作用及其机制尚未得到探索。本研究旨在探讨高选择性 δ(1)和 δ(2)-OR 激动剂在急性失血性休克复苏中的心肌保护作用及其机制。
采用 30%（5ml）全血容量去除法建立成年雄性 SD 大鼠 60 分钟失血性休克模型，然后输注失血和乳酸林格氏液进行 2 小时复苏。在休克结束和复苏前，分别给予 NS、δ(1)-OR 激动剂 TAN-67（10mg/kg）和拮抗剂 BNTX（3mg/kg），以及 BNTX+TAN-67、DMSO、δ(2)-OR 激动剂 Deltorphin II（1mg/kg）和拮抗剂 NTB（2mg/kg），以及 NTB+Deltorphin II（0.5ml）。整个实验过程中测量左心室功能参数。分离心肌线粒体以测定线粒体通透性转换孔（mPTP）的开放情况。电镜观察心肌和线粒体的形态变化。
TAN-67 组和 Deltorphin II 组在复苏过程中的各个时间点的血流动力学指标均高于对照组（P<0.05）。TAN-67 和 Deltorphin II 降低了 mPTP 的开放度，而其拮抗剂 BNTX 和 NTB 则增加了 mPTP 的开放度（P<0.05）。TAN-67 组和 Deltorphin II 组心肌和线粒体损伤减轻。
δ(1)-OR 激动剂 TAN-67 和 δ(2)-OR 激动剂 Deltorphin II 通过靶向急性失血性休克大鼠的 mPTP 来保护心脏。
