cAMP热限及其与致热原热限的关系的研究

本实验室最新的研究资料表明,中枢内cAMP的生成受限可能是致热原性发热时热限的重要成因之一。本研究结果显示:(1)在一定范围内,家兔侧脑室注射Db-cAMP(Dibutyryl cyclic AMP,双丁酰环腺苷—磷酸)可以引起依赖于剂量的发热效应,而大剂量时可出现cAMP热限;(2)非热限剂量Db-cAMP加非热限剂量EP(endogenous pyrogen,内生致热原)负荷,表现出两者致热效应的叠加;(3)Db-cAMP热限加热剂量EP负荷,发热高度没有突破EP热限或Db-cAMP热限水平;Db-cAMF热限加热限剂量ET(endotxin,内毒素)负荷,发热高度接近ET热限,但明显高于Db-cAMP热限水平。作者推论,cAMP热限的产生可能与中枢内cAMP的作用点达到饱和有关。在EP热限或ET热限的成因中,既有中枢内cAMP生成受限,又可能同时有中枢内cAMP作用点达到饱和、或cAMP后继介质生成受限。ET热限的构成,除cAMP以外,同时可能还有其它因素参与。

Studies on hyperthermic ceiling of cAMP and its relation to hyperthermic ceiling of pyrogen

Some results obtained by others showed the limitation of cyclic 3', 5'-adenosine monophosphate (cAMP) increase within the brain might be an important factor in endogenous pyrogen (EP) hyperthermic ceiling (HC) or endotoxin (ET) HC. The results obtained from our experiments indicated: (1) Lateral cerebro-ventricular administration of dibutyryl cAMP (Db-cAMP) induced dose-dependent fever in rabbits. But there was no further increase in body temperature when the fever reached a certain height, even if Db-cAMP doses were increased progressively, "a flat slope" appeared in the dose response curve. This is termed "cAMP HC" by the authors. (2) Level of fever cavsed by non-HC dose Db-cAMP with non-HC dose EP was markedly higher than that of non-HC dose EP or non-HC dose Db-cAMP, and was similar to the sum of action caused by non-HC dose Db-cAMP and non-HC dose EP. (3) Similar were the levels of HC caused by EP, Db-cAMP and Db-cAMP with the charge of HC dose EP. But the level of HC caused by ET or Db-cAMP HC with the charge of HC dose ET was higher than that of cAMP.The authors deduce that the cAMP may be an important central mediator in pyrogen-induced fever; the cAMP HC developed may be a result of saturation of cAMP action site within the brain or the limitation of production of other mediators induced by cAMP; the formation of EP HC or ET HC may be influenced not only by the limitation of cAMP increase, but also by the saturation of cAMP action site, within the brain; ET fever and ET HC differed greatly from those of EP; besides cAMP, other factors may be involved in the formation of ET HC.