家兔发热诱导热休克转录因子1聚合对体温及下丘脑cAMP含量的影响  

Fever-induced polymerization of heat shock factor 1 influences body temperature and cAMP content in hypothalamus of rabbits

作　　者：白宁[1] 金莲锦[2] 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,沈阳110001 [2]牡丹江医学院附属红旗医院,牡丹江157011

出　　处：《第二军医大学学报》2008年第7期773-777,共5页Academic Journal of Second Military Medical University

基　　金：国家自然科学基金(302701918);高等学校博士学科点专项科研基金(2006159004)~~

摘　　要：目的:观察热休克转录因子1(HSF1)聚合对家兔脂多糖(LPS)诱发性发热反应的影响,并研究其与下丘脑cAMP含量变化的关系,以探讨HSF1是否参与热限作用及可能的机制。方法:家兔随机分成4组:(1)对照组(N):注射无水乙醇;(2)槲皮素组(Q):注射槲皮素-无水乙醇溶液(2.5/μmol/L);(3)LPS组(L):注射无水乙醇,10min后静脉注射脂多糖(LPS,0.5μg/kg);(4)槲皮素+LPS组(Q+L):注射槲皮素-无水乙醇溶液(2.5μmol/L),10min后静脉注射LPS(剂量同L组)。通过复制LPS性发热家兔模型诱导HSF1聚合,观察聚合的HSF1对LPS性发热效应的影响,并用放射免疫法检测下丘脑中cAMP含量的变化。结果:Q+L组与L组比较,在240～360min期间即时体温与基础体温之差(△T)差异显著(P<0.05),6h体温反应指数(TRI6)为8.32±0.63,明显高于L组(P<0.01)。Q+L组各时间点的cAMP含量与L组相比明显增加(P<0.01)。HSF1三聚体的表达从致热后60min开始逐渐增多,达到体温最高值时(180min)为对照水平的1.77倍,此后,随着HSF1三聚体表达水平的进一步升高,体温逐渐下降。而预先使用槲皮素抑制HSF1的聚合,Q+L组的HSF1三聚体的表达量在60、180、240、360min组均低于对应的L组(P<0.05),HSP70表达水平相应降低;cAMP含量增多,发热幅度升高,发热时程延长。结论:聚合的HSF1对LPS性发热有抑制效应,此作用可能与抑制下丘脑cAMP的生成有关。Objective： To observe the effects of heat shock factor 1 （HSF1） polymerization on the LPS-induced febrile reaction in rabbits and study its relationship with cAMP content, so as to investigate whether HSF1 plays a role in the fever limiting function and the possible mechanisms. Methods： Seventy rabbits were randomly divided into 4 groups： （ 1 ） Normal control group（ N）, injection of ethanol in t he lateral venericle ; （2） Quercetin group（Q）, injection of quercetin and ethanol solution （2.5 μmol/L） ; （3） i.ipopolysaccharide group（ L）, LPS（ 0.5μg/kg） was injected 10 min after injection of ethanol; （ 4 ） Quercetin plus LPS group（Q＋L）,LPS was injceted 10 min after injection of quercetin plus ethanol（2.5 μmol/L）. The polymerization of HSF1 was induced by reproducing LPS-induced febrile reaction model in rabbits to assess the influence of polymerized HSF1 on LPS-induced febrile reaction. The content of cAMP in the hypothalamus was measured by radioimmunoassay. The expression of HSF1 and HSP70 protein in the hypothalamus was detected by Western blotting. Results： The difference between basal temperature and temperatures of defined time points △T （240-360 min） of Q＋L group was significantly higher than that of L group （P〈0.05） ; TRLwas 8.32±0.63 in Q＋L group,significantly higher than that of L group （P〈0.05） ; and the contents of cAMP of Q＋L group at all time points were significantly higher than those of the L group （P〈0. 01）. Polymeric HSF1 content started to increase at 60 min after LPS injection and obviously increased when the body temperature reached the peak （180 min,being 1.77 folds that of the control level） ; then with the increase of HSF1 trimerization,the body temperature beganto decrease. When pretreatment with quercetin was performed to inhibit polymerization of HSF,the levels of HSF1 trimerization at 60 min,180 min,240 min,and 360 min in Q＋L group were significantly lower than those in the corresponding L grou

关 键 词：发热 热限 热休克因子1 环AMP 体温 

分 类 号：R364.6[医药卫生—病理学]