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Inhibition Of Bombesin To IL-1β-induced Fever And Effects On PGE2 Level In Hypothalamus And Plasma

Posted on:2005-03-12Degree:MasterType:Thesis
Country:ChinaCandidate:L ZhangFull Text:PDF
GTID:2120360125969762Subject:Physiology
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IntroductionBombesin (BN) is a kind of polypeptide originally isolated from amphibian skin. It was found in the brain later. It is a member of neuromodulators and participates in thermoregulation probably by inhibiting thermogenesis. It is one of the most potent substances that have thermoregulatory effects. Prostaglandin E2 ( PGE2) is one of the most important central febrile mediator, which can induce fever by stimulating cold - sensitive neuron in organum vasculosum laminae ter-minalis (OVLT).Interlukin (IL) - 1 is a kind of endogenous pyrogen. Typical febrile reaction can be induced through i. v. injection of IL - 1 in rats and rabbits. Investigation shows IL - 1 can induce fever by vagus nerve in abdominal cavity and it is dose - dependent. Latest research confirms IL - 1R I mRNA expression exists at sensory neuron of vagus nodular ganglia. Cental fever induced by IL - 1 can be mediated through central febrile mediator - Corticotropin releasing hormone. Previous research by our laboratory demonstrated that opiate receptor (mainly receptor) in POA and arcuate nucleus participates in or mediates IL -13 induced fever. In this experiment we use BN inhibiting IL - 1 induced fever to explore the relationship between BN and PGE2, by detecting content of PGE2 in POA and plasma.Materials and Methods1. Animals and body temperature measurementHealthy male S - D rats, weighting 180 -220g, obtained from China Medical University Animal Center, were housed individually under controlled temper-ature (20 2) C and humidity (50 2)% , and light-dark conditions (lights on 6 AM, lights off 6 PM). Food and water were available ad libitum. Digital thermometer probe were inserted 6 centimeters in rats' rectum. Value was recorded after stabilization. Rats were habituated to experimental procedures by non-invasive 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. All experiments were carried out between 7AM and 2PM.2. Implantation of brain cannulas and intracerebroventricular microinfusion Under intraperitoneal anesthesia ( ketamine hydrochloride and xylazine) , a1mm 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. When it was over, cannula's positions were checked to discard incorrect ones. During intracerebroventricular microinfusion, make sure that administration velocity is consistent.3. sample collects and assays4 ml blood was taken from inferior vena cava, and immediately reversed several times in empty injector. Then centrifuged and the supernatants were conserved at -30 . Hypothalamus tissue was put into liquid nitrogen simultaneously. 10 mg tissue was weighted to assay content of PGE2 with radioimmunoas-say.ResultsIntracerebroventricular administration of IL - 1 (3 induced increase in body (core) temperature, PGE2 level was significantly higher than control group (P <0.05). Administration of BN reduced body temperature, PGE2 was significantly lower compared with control ( P <0.05). While administration with IL -ip 10 minutes after BN microinfusion caused body temperature elevation post earlier reduction. The shifting magnitude was between BN group and IL - 1 (3group, the same with PGE2 content ( P <0.05 ).DisscusskmPreoptic - anterior hypothalamus area ( PO/AH) has been accepted as thermoregulation center. Veale et al extirpated bilateral POA of rabbits, and then infused with human PGE2 in this area or ventricle, but could not induce fever of rabbits. That demonstrated that febrile response of PGE2 could act through receptors on POA membrane. Recent studies have confirmed that PGE2 has very important intermediate function in fever. Our data also demonstrated endogenous pyrogen IL - 1 (3 could increase body te...
Keywords/Search Tags:bombesin ( BN ), interlukin (IL ) - 1 β, Prostaglandin E2 (PGE2), fever
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