不同浓度内生致热原的发热效应,脑脊液中cAMP的反应及“热限”的研究

为研究cAMP在发热机制及“EP热限”中的作用,用家兔血细胞加微量内毒素体外培育制备内生致热原(EP),在72只家兔的实验中观察不同剂量EP静脉注射后4小时发热效应;在65只家兔的实验中观察不同剂量EP静脉注射后1小时发热效应及血浆和脑脊液中cAMP含量变化。实验结果表明:(1) 在一定范围内,EP的发热效应随注射剂量的递增而增强,但当发热达到一定强度后,便不再随EP剂量的继续增加而加强,在剂量—效应曲线上出现“平坡”,作者称之为“EP热限”。(2)注射EP后1小时,血浆中cAMP无明显变化,而脑脊液中cAMP的浓度却明显增加,且与发热效应呈非常显著的正相关关系。(3) 当注射大剂量EP出现“热限”时,脑脊液中cAMP的增长也受限。作者推论:脑脊液中cAMP的变化不是来自血浆,cAMP很可能是EP发热的重要中枢介质,cAMP的增长受限可能是“EP热限”的重要成因。

Study on fever action, cAMP response in cerebrospinal fluid and hyperthermic ceiling by endogenous pyrogen in different concentration

For the purpose of studying the reaction of cAMP in fever pathogenesis and "EP hyperthermic ceiling", endogenous pyrogen(EP) was prepared in vitro by incubating the rabbit whole blood with a small quantity of endotoxin. After EP in different doses was intravenously injected in 72 rabbits fever was observed in 4 hrs. The fever induced and the changes of cAMP contents in plasma and cerebrospinal fluid (CSF)were assayed in 1 hr after EP was given intravenously in different doses in another 65 rabbits.The results obtained demonstrated: (1)The increase of febrile response within certain limits by EP was developed with the increase of EP doses given progressively, but there was no more increase when the fever had reached a certain intensity "A flat slope" appeared in the doseresponse curve, which is termed "EP hyperthermic ceiling" by the authors; (2) One hour after the injection of EP and following the fever,there was no obvious change of cAMP in plasma, while the concentration of cAMP in CSF was markedly increased, which was apparently correlated positively to the fever reaction; (3)During the occurrence of hyperthermic ceiling after a Iarge dose of EP was given,the limitation of the increase of cAMP in CSF could also be seen. The authors deduced from above that the change of cAMP in CSF was not resulted from plasma. The cAMP might be an important center mediator in EP-causing fever,while the limitation of its increase might be an important contributing factor in"EP hyperthermic ceiling".