| INTRODUCTIONBombesin (BN) is a kind of braingut petide, which has wide physiological functions. It is one of the most potent substances that have thermoregulatory effects. Its function of reducing body temperature has close relation with environment temperature. When the outer circumstance temperature altered, function of Bombesin to animals changed too. But the mechanism is still unclear.cAMP is an important central mediator in febrile response. It is deeply concerned by researchers for thermoregulation. Interleukin (IL) -1β is a kind of endogenous pyrogen, which is synthesized and released by monocyte/macro-phage. Kinds of animals studies show that IL - 1β can induce typical febrile response , and is dose - dependent.The present study observed Bombesin reduce normal rat body temperature and IL - 1β - induced fever on different temperature conditions, and measured cAMP level in PO/AH and plasma, so as to explore the relationship between BN' s reducing temperature and cAMP level.MATERIALS AND METHODS1. animals and surgeryMale Sprague -Dawley rats, weighting 180 -220g, purchased from China Medical University Animal Center, were housed individually. Room temperature was kept at (20 2) ℃. Food and water were available ad libitum. All experiments were carried out between 7AM and 2PM. Under intraperitoneal anesthesia( ketamine hydrochloride and xylazine) , a 1mm of diameter cannula was implanted into the lateral ventricle according to Louis J. Pellegrine, and the cannula was anchored with dental acrylic, sealing off upper end. Rats were individually housed 7 days before experiments. One hour ahead put the rats in refrigerator. Digital thermometer probe were inserted 6 centimeters in rats'rectum. Value was recorded after stabilization. Rats were habituated to experimental procedures by noninvasive handling daily for 7 consecutive days before the experiments. After administration, rectal temperature at 15, 30, 45, 60, 90, 120 and 180 minutes was recorded respectively. Mean of three values 1 hour before administration was taken as baseline of pre - handling. When the experiment was over, cannula's positions were checked to discard incorrect ones.2. cAMP levelsFrom inferior vena cava 4 ml blood was taken, centrifuged and the superna-tants were conserved at -30). Hypothalamus tissue was put into liquid nitrogen simultaneously. 50 mg tissue was weighted, homogenate, centrifuged and assay concentration of PGE2 .with radioimmunoassay.3. Statistical AnalysisResults were presented as mean SD. Change in body temperature were presented and analyzed with AT and thermo - response index. Data were analyzed using T - test.RESULTS1. At room temperature or 4 t, in the febrile rats induced by i. c. v. injection of IL - 1 β, cAMP level in PO/AH and plasma was significantly higher;2. At room temperature or 4 , bombesin could reduce normal body temperature of rats. Content of cAMP in hypothalamus was lower;3. On the two temperature conditions, fever induced by IL -1β could be inhibited by pretreatment with bombesin; Content of cAMP in hypothalamus was lower compared with control group.DISSCUSSIONIn the present study, intracerebroventricular administration of IL - 1β induced increase in body temperature, cAMP level was significantly higher than control group. This was consistent with previous report. cAMP level in blood was elevated too. That demonstrated that IL - 1β induced fever related to cAMP increase. As to the mechanism of cAMP level increased in brain, latest data showed endogenous pyrogen might cause cAMP level increasing by elevating Na+/Ca2+ ratio, namely EP-->Na+/Ca2+ ratio in PO/AH cAMP . So we could further explore the mechanism of IL - 1β induced cAMP level rise by simultaneously measuring EP-->Na+/Ca2 + ratio in PO/AH.Our research observed intracerebroventricular administration of bombesin reduced body temperature, 30 minutes or so obviously and45minutes at the nadir at 4 temperature. While at room temperature the nadir time was 60 minutes. cA... |
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