通过激活TRPV1达到快速有效治疗性浅低温方法的探讨  

Synergistic effect of TRPV1 activation on promoting mild therapeutic hypothermia

作　　者：岳静[1] 陈雯[1] 向桂芳[1] 李新华[2] 周碧云[2] 艾玲[2] 陈明兵[2] 

机构地区：[1]华中科技大学同济医学院附属同济医院生殖医学中心,湖北武汉430030 [2]华中科技大学同济医学院附属同济医院麻醉学教研室,湖北武汉430030

出　　处：《中国病理生理杂志》2015年第9期1633-1636,共4页Chinese Journal of Pathophysiology

基　　金：湖北省自然科学基金资助项目(No.2013CFB130;No.2013CFB119;No.2013CFB140)

摘　　要：目的：通过二氢辣椒碱（DHC）调控瞬时受体电位阳离子通道香草酸亚型1（TRPV1）,探讨达到治疗性浅低温的方法。方法：（1）观察不同剂量DHC（2、3和4 mg/kg）皮下注射对小鼠体温的影响,以20%DMSO溶于生理盐水为对照组,寻求达到目标温度（32~34℃）所需的最佳剂量;（2）清醒CD-1小鼠单次皮下注射最佳剂量DHC后,按1 mg·kg-1·h-1的速度持续输注DHC,观察是否有快速降温及维持治疗性浅低温的最长时间;（3）相同剂量DHC皮下注射于成年（9~10周）和老年（24~27月）小鼠,观察小鼠体温变化。结果：（1）单次注射2mg/kg DHC可在15 min内达到治疗性浅低温;（2）单次注射2 mg/kg DHC后,按1 mg·kg-1·h-1的速度持续输注DHC可快速降温,还可维持治疗性浅低温6 h;（3）DHC介导的低体温在不同年龄模型中均适用。结论：DHC通过激活TRPV1通路可产生治疗性低体温,该方法可达到更强和更久的中心体温降低,在不同年龄模型中均适用。AIM：To look for a way of produ cing mild therapeutic hypothermia through regulating transient re-ceptor potential cation channel subfamily V member 1 （TRPV1） pathway by dihydrocapsaicin （DHC）.METHODS：Mice were subcutaneously injected with DHC at different doses （2 mg/kg, 3 mg/kg and 4 mg/kg） in order to find the best dose for reaching the target temperature （32~34℃）.20%DMSO dissolved in normal saline was used as control group .After a single subcutaneous injection of DHC at an optimal dose was given , awaken CD1 mice were continuously infused with DHC at dose of 1 mg？ kg-1？ h-1 for providing a more rapid and stable temperature drop and duration of therapeutic mild hypothermia.The adult mice （9~10 weeks） and aged mice （24~27 months） were subcutaneously injected with DHC at the same dose, and the changes of the body temperature were monitored .RESULTS：DHC at 2 mg/kg resulted in a de-crease in the core temperature within the target therapeutic range （32~34 °C）.After a bolus dose （2 mg/kg） was deliv-ered at 0 min followed by continuous infusion （1 mg？ kg-1？ h-1 ） beginning at 30 min, a rapid drop of body temperature to 34 ℃was achieved and the body temperature was maintained within the ranges of 32 to 34℃for the duration of the 6 h continuous infusion .DHC-mediated hypothermia did not lose its effectiveness in the adult and aged models .CONCLU-SION：DHC-induced activation of TRPV1 pathway produces mild therapeutic hypothermia .Besides, this method achieves stronger and longer center hypothermia and is suitable for the animals at different ages .

关 键 词：瞬时受体电位阳离子通道 治疗性浅低温 体温调节 

分 类 号：R363[医药卫生—病理学] R459.4[医药卫生—基础医学]