A Study Of The Therapeutic Effects Of Apoliprotein A-I On Endotoxemia In Mice Induced By Lipopolysaccharide

Background: Endotoxin also named lipopolysaccharide(LPS), which is the adventitial essential component of Gram negative bacteria. Endotoxemia and relevant acute lung injury, acute respiratory dysfunction syndrome and multiple organ dysfunction syndrome are the most important reasons for patients infection leading to death. Apolipoprotein AI is the main apolipoprotein of high density lipoprotein which can bind to LPS directly or indirectly and neutralize the toxicity of LPS.Objective:In this study, We investigated the therapeutic effects and the possible mechanisms of ApoA-I on endotoxemia induced by LPS through establishing the model of endotoxemia in mice.Methods: Mice were randomly divided into Normal Saline group, ApoA-I low-dose group (10mg/kg), ApoA-I high-dose group (50mg/kg), LPS group (LPS+D-galactose), D-galactose group (Normal Saline+D-galactose). Established the endotoxemia model in mice by injected LPS at abdominal; To determination the levels of TNF-α, IL-6 and IL-8 in the serum by radioimmunoassay kit; Observed the histopathological changes by the pathological section from liver and lung tissues; We detected the expression of mRNA of LPS receptor CD14 in different mice tissues by reverse transcription-polymerase chain reaction (RT-PCR); To detecte the expression of protein of LPS receptor CD14 in different mice tissues by western-blotting (WB).Result: ApoA-I can significantly inhibit LPS-induced increasing of TNF-α, IL-6 and IL-8(P<0.05, P<0.01, P<0.01, respectively). And the inhibition of high-dose ApoA-I (50mg/kg) was more significantly compared with low-dose ApoA-I (10mg/kg) (P<0.05, P<0.01, P<0.01, respectively); Histopathological analysis of the lung and Liver tissues were performed that ApoA-I could attenuate LPS-induced damage; The increasing level of mRNA expression of CD14 challenged with LPS(P<0.01) were reduced significantly in different tissues after the ApoA-I treatment (P<0.01); and the mRNA expression of CD14 of different tissues in the high does ApoA-I group (50mg/kg) were decreased more significantly compared with the lower does ApoA-I group(10mg/kg)(P<0.05); The increasing level of protein expression of CD14 challenged with LPS(P<0.01) were reduced significantly in different tissues after the ApoA-I treatment (P<0.01); and there was no significance for the level of protein expression of CD14 of different tissues in the high and lower does ApoA-I (50mg/kg) group (P>0.05).Conclusion: This study suggested that 1)ApoA-I can reduce the concentration of TNF-α, IL-6 and IL-8 in plasma on mice induced by LPS; 2)ApoA-I can attenuate LPS-induced acute lung and Liver injury; 3)ApoA-I significantly reducing the mRNA and protein expression of CD14 in Heart, lung, Liver and kidney on mice induced by LPS.