The Effects Of Antivirus Ⅰ On Experimental Fever And Its Mechanism

Objective:To investigate the effects of AntivirusⅠon experimental fever and its mechanism.Methods:Reproduce the models of beer yeast suspension-induced fever in rats,typhoid,paratyphoid vaccine-induced fever and endotoxin-induced fever in rabbits.Observe the effect of AntivirusⅠon experimental fever and explore its mechanism of antipyretic effect.1,Beer yeast suspension-induced fever in rats:On the back of the rat, subcutaneous injection(sc)of 10% draft beer yeast suspension 10mL/kg.6hours later,we will make the administration,the rectal temperatures are measured at the point of 60min,120min,180min and 240min after administration.Observe the changes of temperature and calculate the antipyretic percentage,at last compare the differences among the groups.2,Typhoid,Paratyphoid vaccine-induced fever in rabbits:auricular intravenous injection(iv)of typhoid,paratyphoid vaccine 0.8mL/kg.1h later,we will make the administration,the rectal temperatures are measured at the point of 30min,60min,90min,120min,180min and 240min after administration.Observe the changes of temperature and calculate the antipyretic percentage,at last compare the differences among the groups.3,Endotoxin-induced fever in rabbits:30mins before pyretogenesia, auricular iv of LPS 2μg/kg,observe the changes of temperature in next 180 minutes,after the last temperature is measured,kill the rabbit,down from the hypothalamus,the contents of IL-1β,PGE2 and cAMP are measured.Results: 1,6 hours after sc 10%draft beer yeast suspension 10mL/kg,the temperature was increased about 2.0℃,and compared with the normal,difference was significant(P<0.001).60mins after administration of Paracetamol,fever in rats showed obvious antipyretic effect,role has continued to 240min,compared with the model group difference was significant ( P<0.01 or P<0.001);AntivirusⅠ10mg/kg, 60mins after administration showed antipyretic effect apparently,120~180min reached the peak,role has continued to 240 min,compared with the model group difference was significant(P<0.05 or P<0.01),2.5,5.0mg/kg showed a certain of antipyretic effects on beer yeast suspension-induced fever,but compared with the model group,the difference was not significant(P>0.05).2,1 hour after iv typhoid,paratsyphoid vaccine,the temperature was increased about 1.5℃,and compared with the normal,difference was significant (P<0.001).30mins after administration of Paracetamol,fever in rabbits showed obvious antipyretic effect,role has continued to 240min,compared with the model group,difference was significant ( P<0.001 ) ;30mins after administration,AntivirusⅠ1.3mg/kg showed significant antipyretic effect,role has continued to 180min.60mins after administration,2.6mg/kg showed significant antipyretic effect,role has continued to 240min.30mins after administration,5.2mg/kg showed significant antipyretic effect,role has continued to 240min.Compared with model group,difference was significant(P<0.05～0.001).3,After iv LPS 2μg/kg,the temperature began to rise immediately,and endotoxin-induced fever was showing typical biphasic fever.20mins after pyretogenesia,compared with the control group,model group showed a significant difference ( P<0.001 ) .60mins after administration of Paracetamol,fever in rabbits showed obvious antipyretic effect,role has continued to 150min,compared with the model group difference was significant( P<0.05 or P<0.01 ) ;50mins after administration of AntivirusⅠ, endotoxin-induced fever in rabbits was significantly inhibited,and the antipyretic effect was continued until 210min after administration,compared with the model group difference was significant(P<0.05 or P<0.01).Compared with the control group IL-1βand PGE2 of model group were significantly increased ( P<0.01 ), cAMP decreased significantly( P<0.05 ) .Compared with model group,Paracetamol and AntivirusⅠsignificantly lowered the levels of PGE2 and IL-1β(P<0.05 or P<0.01),and increased cAMP levels significantly(P<0.05).Conclusions:1,AntivirusⅠput beer yeast suspension -induced fever in rats and typhoid,paratyphoid vaccine-induced fever in rabbits a marked inhibition.2,AntivirusⅠs ignificantly inhibited endotoxin-induced fever in rabbits. Antipyretic effect may be related to the inhibition of IL-1βin hypothalamus,that reduce the release of PGE2 and increase the content of cAMP.3,Certify that LPS-induced fever is biphasic fever.PGE2 may cause the emergence of febrile phase I,it may arise from that LPS can damage the blood-brain barrier through direct role in the central nervous system to produce or the LPS in the blood cause the release of other chemical medium,the latters enter the brain and cause the production of PGE2.LPS cause the original cells to release endogenous pyrogen,this may produce the Phase II.AntivirusⅠcan inhibit the LPS-induced fever in phase I and II significantly.So it can be concluded that AntivirusⅠn ot only inhibits the synthesis of PGE2 in central nervous system,but aslo the synthesis in peripheral is blocked.4,In experiment of LPS-induced fever,IL-1β,PGE2 in hypothalamus increased accompanied by the decrease of cAMP.The content of cAMP can be attributed to the increased levels of IL-1βin hypothalamus,IL-1βmediated fever and led to the release of PGE2,PGE2 interacted with the EP3 receptor,the EP3 receptor co-existed with Gi-protein,and Gi-protein can inhibit the activity of AC to decrease cAMP levels.AntivirusⅠinhibited the increase of IL-1β,PGE2 in hypothalamus and increased the levels of cAMP,this can be explained as another important mechanism of antipyretic effect of AntivirusⅠ.This research is not only for the development of AntivirusⅠas antipyretic drugs as a experimental basis,but also a new proposed problems to the domestic research on the mechanism of fever.The changes of cAMP in fever process are to be further verified.