Fever-induced polymerization of heat shock factor 1 influences body temperature and cAMP content in hypothalamus of rabbits / 第二军医大学学报

ABSTRACT

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 the lateral venericle; (2) Quercetin group(Q), injection of quercetin and ethanol solution (2.5 μmol/L); (3)Lipopolysaccharide group(L), LPS(0.5 μg/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 ΔT (240-360 min) of Q+L group was significantly higher than that of L group (P<0. 05); TRI, was 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 began to 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 group (all P<0. 05); meanwhile, the expression of HSP70 was decreased, the content of cAMP was increased, the febrile reaction was intensified and the time course of the febrile reaction was extended. Conclusion: Polymeric HSF1 can inhibit the LPS-induced febrile reaction, which is probably related to the down-regulation of AMP content in the hypothalamus.