Effects Of High Volume Hemofiltration (HVHF) On TLR4 In Shock Dogs Induced By Endotoxin

Objective To investigate the effects of High Volume Hemofiltration (HVHF) on the expression of Toll like-receptors 4 mRNA in shock dogs induced by endotoxin (lipopolysaccharide,LPS)。Method twenty-four healthy hybrid male dogs were selected for this study。All dogs were divided into three groups randomly,eight dogs ,one group。normal comparison did not inject LPS,only mechanic ventilation add a sham treatment; control group and treatment group were injected LPS (650μg/kg) via central vein within 30min to establish model of endotoxin shock. The dogs in treatment group were received the treatment of HVHF add mechanic ventilation, while control group was just a sham treatment add mechanic ventilation。HR,mAP,PAP,CVP,PAWP,CO were recorded at between baseline and established model after HVHF respectively and we calculated PVR and SVR。Contents of TNF-α,IL-6,IL-10 in circulation at 0h,1h,2h,4h were measured by radioimmunity.。All dogs'lung were dissected from their chest 4h after HVHF.they were reserved in liquid nitrogen cylinder。The expression levels of TLR4mRNA in all group were measured by RT-PCR。Results 1,mAP,CO,HR decreased gradually after LPS intravenously while PAP,PAWP,CVP,PVR,SVR increased gradually。When mAP decreased to 20% baseline,the model was established successfully。All parameters were obviously significant compared to baseline (P<0.01)2.radioimmunity showed that TNF-α,IL-6,IL-10 in therapy group decreased significantly at 1h after HVHF and presented continuous decrease trend (P<0.01) while those in control group had no change compared to baseline (P>0.05). Between two groups, TNF-α,IL-6,IL-10 in treatment group at any time point were lower than those in control group significantly(P<0.01).RT-PCR showed that mRNA expression of TLR4 in blank comparison,control group,treatment group were 0.895±0.048,0.987±0.036,0.931±0.019 respectively at 4h after HVHF,comparing with normal comparison , control group can significant up-regulate mRNA expression of TLR4(P<0.01) ; comparing with control group , HVHF treatment group can down-regulate mRNA expression of TLR4(P<0.01)。Correlation Analysis reveal:Significant correlation was found between tissue TLR4 mRNA expression and Contents of TNF-α,IL-6,IL-10 in circulation(P<0.05),Correlation coefficient between tissue TLR4 mRNA expression and Contents of TNF-α,IL-6,IL-10 in circulation were 0.821,0.542,0.610 respectively。Conclusion There are some levers expression in normal dog'lung tissue; endotoxin(lipopolysaccharide,LPS)can up-regulate mRNA expression of TLR4,putting forward inflammatory response ; HVHF can down-regulate mRNA expression of TLR4,cutting down inflammatory response。The mechanism of HVHF to endotoxin shock were continuously to eliminate many inflammatory medators-like cytokines by Convection and adsorption,cutting-down"positive feedback Regulation"mRNA expression of TLR4;keep internal environment stable,Reduce Stress response,down-regulateing mRNA expression of TLR4。this study may offer an new theoretical basis for clinic treating septic shock。...