LPS致热家兔诱导HSF1聚合对体温及脑内AVP含量的影响  

Effect of the polymerization of HSF1 on the febrile response and the content of vasopressin arginine in brain in LPS-induced fever rabbits

作　　者：金莲锦[1] 白宁[1] 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,辽宁沈阳110001

出　　处：《中国药理学通报》2008年第1期45-49,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No30270198);高等学校博士学科点专项科研基金资助项目(No2006159004)

摘　　要：目的探讨热休克因子1(HSF1)在脂多糖(LPS)致家兔发热过程中的作用及机制。方法70只家兔随机分为4组:正常对照组(N)、槲皮素组(Q)、脂多糖组(L)和槲皮素+脂多糖组(Q+L)。连续观察体温变化;Westernblot方法检测不同实验条件下下丘脑HSF1和热休克蛋白70(HSP70)的表达;放射免疫法检测下丘脑及腹中隔区(VSA)精氨酸加压素(AVP)含量的变化。结果①各组体温变化最大值(△Tmax)由低至高顺序为:Q组<N组<L组<Q+L组;其中,Q+L组与L组比较,△T(240～360min期间)及体温反应指数TRI6均增高(P<0.05)。②各组VSA中的AVP含量与体温变化呈正相关(r=0.913,P<0.01)。Q+L组与L组比较,VSA中的AVP含量增高(240～360min期间,P<0.05)。③HSF1三聚体的表达从致热后60min(体温升高1.32±0.24℃)起逐渐增多,达到体温最高值时(180min)为对照水平的1.752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。应用槲皮素(quercetin,Que)可抑制HSF1的聚合,可见当HSF1的聚合被抑制时HSP70表达水平相应降低。结论发热时温度升高到一定程度可诱导下丘脑HSF1聚合,HSF1的聚合可限控体温的升高程度,而VSA中AVP含量的变化主要与体温升高的幅度有关。Aim To observe the effect of the polymerization of HSF1 on the febrile response in fever rabbits, and further to investigate HSF1 action in thermoregulation and the possible central mechanism. Methods 70 rabbits were divided randomly into 4 groups- the control group （N）, the quercetin group （Q）, the LPS-feverish group （ L）, the quercetin ＋ LPS-feverish group （ Q ＋ L）. Changes in body temperature were continually observed; the expression of HSF1 and HSP70 in hypothalamus was detected by Western blot; the content of AVP in hypothalamus and VSA was measured by radioimmunoassay. Results ① The sequence of the maximum change of temperature （△Tmax ） from low to high ： group Q 〈 group N 〈 group L 〈 group Q ＋ L; AT （240 - 360 min） and TRI6 of group Q ＋ L was signifi- cantly higher than that of group L （ P 〈 0. 05 ）. ② The content of AVP and the body temperature were positively correlated（r =0. 913,P 〈0. 01 ）. The content of AVP in VSA of group Q ＋ L was significantly higher than that of group L （ P 〈 0. 05,240- 360 min）.③ The content of HSF1 trimerization was obviously increased at 60 min（ AT： 1.32 ± 0. 24℃ ） after the injection of LPS and it was gradually increased when the body temperature reached the peak, then the temperature began to decrease. At the same time, the expression of HSP70 decreased when the polymerization of HSF1 was inhibited. Conclusion During the period of LPS-induced fever, it was possible that the polymerization of HSF1 limited the rise of the body temperature through some mechanisms. The change of the content of AVP in VSA was related to the rise of the tempera- ture.

关 键 词：脂多糖 发热 热休克因子1 精氨酸加压素 槲皮素 

分 类 号：R-332[医药卫生] R282.71