Synergistic effect of TRPV1 activation on promoting mild therapeutic hy-pothermia / 中国病理生理杂志

ABSTRACT

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-SIONDHC-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 .