μ,δ,κ阿片受体在创伤失血性休克大鼠心血管功能抑制中的作用

Importance of μ,δ and κ Opioid Receptors in Cardiovascular Depression Following Traumatic Hemorrhagic Shock in Rats

目的探讨μ，δ和κ阿片受体与创伤失血性休克大鼠心血管功能抑制的关系。方法用大鼠创伤失血性休克模型，观察创伤失血性休克后大鼠心脏和脑μ，δ和κ阿片受体变化及其与血流动力学指标的变化的关系；观察δ和κ阿片受体特异性拮抗剂对创伤失血性休克大鼠血流动力学指标的影响。结果创伤失血性休克后，大鼠心脏和脑δ和κ阿片受体数目明显升高，亲和力无明显变化，心脏和脑的δ和κ阿片受体数目升高与创伤失血性休克后大鼠血流动力学指标下降呈显著负相关。δ和κ阿片受体特异性拮抗剂可明显逆转创伤失血性休克大鼠血流动力学指标的下降。结论δ和κ阿片受体在创伤失血性休克心血管功能抑制中起重要作用。

Aim To investigate the importance of μ, δ and κ opioid receptors in the cardiovascular depression following traumatic hemorrhagic shock, elucidate the facts that the subclass of these opioid receptors is involved in the pathogenesis of traumatic hemorrhagic shock. Methods With a model of traumatic hemorrhagic shock rat, the relationship between the changes of myocardial and brain μ, δ and κ opioid receptors and cardiovascular functions and effects of δ and κ opioid receptor antagonists on hemodynamic parameters of traumatic hemorrhagic shock rats were observed. Results The number of myocardial and brain δ and κ opioid receptors significantly increased, and they were significantly associated with the decreased hemodynamic parameters such as mean arterial pressure (MAP), left intraventricular systolic pressure (LVSP), the maximal rate of the change of intraventricular pressure (±dp/dtmax) and the area of pdp/dt vector loop (Lo). However, μ opioid receptor of heart and brain did not obviously alter and δ opioid receptor antagonist ICI78, 864 and κ opioid receptor antagonist Norbinaltorphimine (50μg, icv) could significantly reverse those decreased hemodynamic parameters of traumatic hemorrhagic shock rats. Conclusion These results suggest that opioid receptors, especially δ and κ opioid receptors, are closely related to the pathogenesis of traumatic hemorrhagic shock, and they play an important role in the depression of cardiovascular function following traumatic hemorrhagic shock.