缝隙连接抑制剂在重度失血性休克兔脑损伤延生复苏中保护作用的研究

Research of the protect role of gap-junction inhibitor on rabbits with brain injury as a result of severe hemorrhagic shock in suspended animation

目的探讨缝隙连接抑制剂在重度失血休克兔脑损伤延生复苏中保护作用的机制,为延生复苏提供新的临床策略。方法 24只家兔随机分为四组:A组(传统复苏组)、B组(低温延生复苏组)、C组(辛醇延生复苏组)、D组(低温+辛醇延生复苏组),每组6只。所有动物麻醉后,机械通气,动静脉插管、心电监测。采用改良的Wiggers法制备重度失血性休克动物模型,模拟临床将该模型分为三期:即创伤失血期,院前救援期,院内复苏期.处死后取右半脑组织作脑组织含水量检测,取海马组织作Cx43 Western blot;并留取部分脑皮层组织作Cx43、AQP-4免疫组化检测。结果 B、C、D组脑组织含水量比较A组明显降低(P<0.05);Cx43的免疫组化、Western blot示B、C、D组与A组相比表达明显增多(P<0.05),具有显著性差异,但B、C、D组之间没有明显差异。APQ-4的表达:B、C、D组与A组相比明显减少(P<0.05),B、C、D组之间没有明显差异。结论 GJ抑制剂有助于重度失血性休克兔缺血性脑损伤后延生复苏;GJ抑制剂和低温在重度失血性休克缺血性脑损伤延生复苏中作用相似;低温在重度失血性休克缺血性脑损伤延生复苏中有可能是通过阻断GJ/CX43下调APQ-4而起作用的。

【Objective】 To investigate the protect role of gap-junction inhibitor on rabbits with brain injury as a result of severe hemorrhagic shock in suspended animation,and to explore the new clinic strategy in suspended animation.【Methods】 24 rabbits were randomly divided into 4 groups（n =6,each）： traditional resuscitation group（group A）;hypothermy resuscitation group（group B）;octanol resuscitation group（group C）;and hypothermy＋octanol resuscitation group（group D）.After anesthetized,all rabbits were mechanical ventilated,intubated through arteries and veins,and monitored by electrocardiogram monitor.After the model of rabbits with severe hemorrhagic shock was established by adopting improved Wiggers’ way,the resuscitation period was divided three periods： traumatic hemorhagic period,pre-hospital treatment period,and in-hospital cardiopulmonary resuscitation period.The changes of Brain water content,the expression of Cx43 in the rabbit’s hippocampus,and Cx43 and AQP-4 in rabbit’s brain mantle were compared.【Results】 Brain water content in group B,group C and group D was decreased compared group A.The expression of Cx43 which was detected by west-blot and immunohistochemisty in group B,group C,group D was improved（P 〈0.01） compared with A group.There were no significant differences among group B,group C,group D.The expression of AQP-4 was decreased in group B,group C and group D compared group A,while there were no significant differences among the three groups.【Conclusion】 It is advantageous for rabbits brain injury as a result of severe hemorrhagic shock in suspended animation by GJ inhibitor.Therapy of hypothermia and GJ inhibitor in suspended animation has the similar the protective effect on rabbit’s brain injury.It’s possible for hypothermia to work by the way of GJ blockade in suspended animation.