TRPV1对LPS致热大鼠体温及下丘脑中Ca^(2+)浓度和cAMP含量的影响  

Effects of TRPV1 on LPS-induced fever and the content of Ca^(2+) and cAMP in hypothalamus in rats

作　　者：王乐[1] 王兰兰[1] 曹宇[1] 

机构地区：[1]中国医科大学基础医学院生理学教研室,辽宁沈阳110001

出　　处：《中国药理学通报》2009年第1期51-55,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No30270198);高等学校博士学科点专项科研基金资助项目(No2006159004)

摘　　要：目的探讨TRPV1在脂多糖(LPS)致大鼠发热过程中的作用和机制。方法48只♂SD大鼠随机分为4组,正常对照组(N)、capsazepine组(CPZ)、LPS组(LPS)和capsaz-epine+LPS组(CPZ+LPS)。连续观察体温变化;在发热高峰期通过颈椎脱臼迅速处死动物,以Fura-2/AM为荧光指示剂,测定下丘脑细胞内[Ca2+]i;应用放射免疫法检测下丘脑中cAMP含量的变化。结果①各组体温变化最大值(ΔTmax)由高至低顺序为:CPZ+LPS组>LPS组>CPZ组>N组;其中,CPZ+LPS组与LPS组比较,ΔT(300~480 min期间)及体温反应指数TRI8均增高(P<0.01);②在发热高峰期,CPZ+LPS组[Ca2+]i明显低于其它3组(P<0.01);③CPZ+LPS组cAMP含量与其它组比较增多(P<0.01)。结论capsazepine可能通过阻断下丘脑TRPV1通道,改变细胞内钙离子浓度,进而影响LPS性发热过程。Aim To observe the effect of TRPV1 on the febrile response in fever rat, and further to investigate TRPV1 action in thermoregulation and the possible central mechanism. Methods Forty-eight rats were divided randomly into 4 groups：the control group （N）, capsazepine group （ CPZ）, LPS-feverish group （ LPS）, the capsazepine ＋ LPS-feverish group （ CPZ ＋ LPS）. Changes in body temperature were continually ohserved;rats were put to death immediately at the peak of fever, [Ca2＋]i was measured by the technique of Fura-2/AM calcium ions fluorescence indicator; the content of cAMP in hypothalamus was measured by ra- dioimmunoassay. Results （1） The sequence of the maximum change of temperature （△Tmax） from high to low：group CPZ ＋ LPS 〉 group LPS 〉 group CPZ 〉 group N; AT （300 -480 min） and TRIs of group CPZ ＋ LPS was significantly higher than that of group LPS （P〈0.01）;（2） At the peak of fever, [Ca2＋ ]i of group CPZ ＋ LPS was significantly lower than that of the other three（P 〈0.01 ） ;（3） The eontent of cAMP in hypothalamus of group CPZ ＋ LPS was the highest （ P 〈 0. 01 ）. Conclusion It was possible that capsazepine changed intra-cellular [ Ca2＋ ]i by blocking TR- PV1 channel in hypothalamus, and then affected LPS- induced fever.

关 键 词：脂多糖 发热 TRPV1 CAPSAZEPINE CAMP [CA2+]I 

分 类 号：R-332[医药卫生] R322.81