创伤低血容量性休克大鼠脑μ、δ、κ阿片受体变化及其在心血管功能抑制中的作用

The potential role of brain μ,δ and κ opioid receptors in the cardiovascular depression following traumatic hypovolemic shock in rats

目的：探讨创伤低血容量性休克后脑组织μ、δ和κ阿片受体的变化及其与心血管功能抑制的关系，明确这３种阿片受体亚型是哪型或哪几型参与了创伤低血容量性休克的发病过程。方法：用大鼠创伤低血容量性休克模型，观察创伤低血容量性休克后大鼠脑组织μ、δ和κ阿片受体数目、亲和力变化以及与平均动脉压（ＭＡＰ）、左心室收缩压（ＬＶＳＰ）、左心室收缩压最大变化速率（±ｄｐ／ｄｔｍａｘ）等血流动力学指标变化的关系；观察δ和κ阿片受体特异性拮抗剂ＩＣＩ１７４８６４和ＮｏｒＢＮＩ侧脑室给药对创伤低血容量性休克大鼠血流动力学指标的影响。结果：创伤低血容量性休克后，大鼠脑δ和κ阿片受体数目明显增加，亲和力无明显变化；μ阿片受体的数目和亲和力均无明显变化；脑δ和κ阿片受体数目增加与创伤低血容量性休克后大鼠ＭＡＰ、ＬＶＳＰ和±ｄｐ／ｄｔｍａｘ等血流动力学指标下降呈显著负相关（Ｐ均＜０．０１）。δ和κ阿片受体特异性拮抗剂ＩＣＩ１７４８６４和ＮｏｒＢＮＩ可明显逆转创伤低血容量性休克大鼠血流动力学指标的下降。结论：脑组织δ和κ阿片受体在创伤低血容量性休克心血管功能抑制中起重要作用，可能参与了创伤低血容量性休克的发病过程。

Objective:To investigate the potential role of brain μ,δ and κ opioid receptors in the cardiovascular depression following traumatic hypovolemic shock,and to elucidate which subclass of these opioid receptors are involved in the pathogenesis of traumatic hypovolemic shock.Methods:Using a rat model of traumatic hypovolemic shock,changes in brain μ,δ and κ opioid receptors were observed,and hemodynamic parameters such as mean arterial pressure (MAP),left intraventricular systolic pressure (LVSP) and the maximal rate of the change of left intraventricular pressure (±dp/dtmax) were also monitored.Results:Following traumatic hypovolemic shock,the number of brain δ and κ opioid receptors significantly increased,it was significantly associated with the decreased hemodynamic parameters,including MAP,LVSP,and ±dp/dtmax (all P<001).Moreover,intracerbroventricular injection (icv) of δ and κ opioid receptor antagonist ICI 174 864 and Norbinaltorphimine (50 μg,icv)could significantly reverse the decreased hemodynamic responses seen in traumatic hypovolemic shock rats.However,there was no obvious changes in μ opioid receptor of brain in the present study.Conclusions:These preliminary results suggest that brain opioid receptors,especially δ and κ opioid receptors are closely involved in the pathogenesis of traumatic hypovolemic shock,and they play important role in the development of cardiovascular depression following acute hypovolemic shock.