Liu Liang-ming, Hu De-yao, Pan Xue-kun, Lu Ru-quan, Dan Fei-jun
State Key Laboratory of Trauma, Burns, and Combined Injury, The Second Department of Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing 400042, People's Republic of China.
Shock. 2005 Nov;24(5):470-5. doi: 10.1097/01.shk.0000183432.17092.34.
The present available opioid receptor antagonists such as naloxone and naltrexone are not highly receptor selective. They may antagonize mu opioid receptors to affect the pain threshold of the patients with traumatic shock while they exert antishock effects. Therefore, they are not suitable for traumatic shock. It is very important to elucidate the subclass of opioid receptors that are closely associated with cardiovascular depression of traumatic shock and then choose their specific receptor antagonists to treat it. Traumatic shock was used in pentobarbital-anesthetized Wistar rats by right femur fracture plus hemorrhage (fixed hemorrhage at a rate of 20 mL/kg in experiment 1 or hemorrhage to 40 mmHg mean arterial blood pressure for 60 min in experiments 2 and 3), and the changes of myocardial and brain opioid receptors after traumatic shock, the antagonizing effects of mu, delta, and kappa opioid receptor antagonists on the cardiovascular depression of traumatic shock and the antishock effects of delta and kappa opioid receptor antagonists ICI174,864 and Nor-binaltorphimine (Nor-BNI) were observed. The results indicate that after traumatic shock, the number of myocardial and brain delta and kappa opioid receptors were significantly increased that were significantly associated with the decreased cardiovascular functions. mu Opioid receptors in the heart and brain did not change significantly. Intracerebral ventricular administration of ICI174,864 and Nor-BNI significantly antagonized the decreased cardiovascular function after traumatic shock and increased the survival rate of traumatic shock rats, but mu opioid receptor antagonist beta-funaltrexamine did not. Meanwhile, intravenous administration of delta and kappa opioid receptor antagonists ICI174,864 and Nor-BNI also significantly increased the mean arterial blood pressure, improved the hemodynamic parameters, and prolonged the survival rate of traumatic shock rats. These findings suggest that opioid receptors are involved in the cardiovascular depression of traumatic shock, and the subclass receptors are mainly delta and kappa opioid receptors. delta and kappa opioid receptor antagonists have good beneficial effects on traumatic shock.
目前可用的阿片受体拮抗剂，如纳洛酮和纳曲酮，并非高度受体选择性的。它们在发挥抗休克作用时，可能拮抗μ阿片受体，从而影响创伤性休克患者的痛阈。因此，它们不适用于创伤性休克。阐明与创伤性休克心血管抑制密切相关的阿片受体亚类，进而选择其特异性受体拮抗剂来治疗创伤性休克非常重要。采用右股骨骨折加出血的方法，在戊巴比妥麻醉的Wistar大鼠中制造创伤性休克（实验1中以20 mL/kg的速率固定出血，实验2和3中出血至平均动脉血压为40 mmHg并持续60分钟），观察创伤性休克后心肌和脑阿片受体的变化、μ、δ和κ阿片受体拮抗剂对创伤性休克心血管抑制的拮抗作用以及δ和κ阿片受体拮抗剂ICI174,864和诺-苄基内啡肽（Nor-BNI）的抗休克作用。结果表明，创伤性休克后，心肌和脑的δ和κ阿片受体数量显著增加，这与心血管功能下降显著相关。心脏和脑中的μ阿片受体没有明显变化。脑室内注射ICI174,864和Nor-BNI可显著拮抗创伤性休克后心血管功能的下降，并提高创伤性休克大鼠的存活率，但μ阿片受体拮抗剂β-氟纳曲胺则无此作用。同时，静脉注射δ和κ阿片受体拮抗剂ICI174,864和Nor-BNI也显著提高了平均动脉血压，改善了血流动力学参数，并延长了创伤性休克大鼠的存活率。这些发现表明，阿片受体参与了创伤性休克的心血管抑制，且亚类受体主要是δ和κ阿片受体。δ和κ阿片受体拮抗剂对创伤性休克具有良好的有益作用。
