通过激活TRPV1达到快速有效治疗性浅低温方法的探讨

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。

Synergistic effect of TRPV1 activation on promoting mild therapeutic hypothermia

AIM: To look for a way of produ cing mild therapeutic hypothermia through regulating transient receptor 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 decrease in the core temperature within the target therapeutic range(32~34 °C). After a bolus dose(2 mg/kg) was delivered 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.CONCLUSION: 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.