Effects Of Kaempferol Intervention On D-GalN/LPS-induced Acute Hepatic Failure In Mice And Its Mechanism

Objective:Acute hepatic failure(AHF)refers to acute onset,no basic liver disease history,2weeks of hepatic encephalopathy(Ⅱ degree and above),accompanied by the following performance:(1)extreme fatigue,severe gastrointestinal symptoms,such as abdominal pain,bloating,nausea,vomiting,loss of appetite,etc.;(2)short-term jaundice progressive deepening;(3)exclude other causes of bleeding tendency(PTA ≤ 40% or INR ≥ 1.5);(4)liver contraction [1].Inflammation is the mechanism by which the organism forms a mechanism against invasion of pathogens,which contains complex biological processes involving the synthesis and release of numerous cytokines.In the process of inflammation of liver disease,the main inducers include endogenous and exogenous,involving a variety of media and cell signaling pathways,which play a leading role is NF-κB(Nuclear Factor-kappa B)signaling pathway.TNF-α and IL-1β are the main pro-inflammatory cytokines,not only can promote the formation of inflammatory mediators,but also can induce NF-κB signaling pathway expression [2].At present,the study on traditional Chinese medicine compound preparation and traditional Chinese medicine treatment of AHF have achieved corresponding results.It can be seen that the efficacy of Chinese medicine in the treatment of AHF is positive.Chinese medicine extract kaempferol is a genus of flavonols,its role is anti-inflammatory and anti-oxidation.In this study,we investigated the effect of kaempferol on AHF mice,observed the level of liver function and pathological changes of liver tissue,and discussed its mechanism from inflammation.Methods:Healthy C57BL/6 mice,male,the SPF,were randomly divided into normal control group(n=10),AHF model group(n=13)and kaempferol intervention group(n=14).Establishment of AHF model by intraperitoneal injection of D-GalN/LPS.The liver function was measured by detecting serum ALT and AST levels.Histopathological changes of liver were observed by HE staining.The expression of proinflammatory cytokines wasdetected by qRT-PCR.Western blot was used to detect the expression of related molecular proteins in NF-κB signaling pathway.The apoptosis of hepatocytes was detected by TUNEL.Results:The results showed that compared with AHF model group,kaempferol intervention group significantly improved the survival rate of D-GalN/LPs induced AHF mice,improved liver function in mice,reduced the pathological damage of liver tissue and reduced the inflammation of liver response,reduced liver cell apoptosis.(Serum ALT level:normal control group:25.87±3.6,AHF model group:2156.4±541.2,kaempferol intervention group:777.6±68.3,kaempferiae intervention group compare with AHF model group,P<0.05.Serum ALT level:normal control group:33.15±8.54,AHF model group:1788.2±332.4,kaempferiae intervention group:801.5±100.8,kaempferiae intervention group compare with AHF model group,P<0.05.Inflammatory factor m RNA expression:TNF-α/HPRT normal control group:0.2±0.04,AHF model group:106.7±61.3,kaempferol intervention group:35.7±14.6,kaempferol intervention group compare with AHF model group,P<0.05;IL-1β/HPRT normal control group:0.2±0.04,AHF model group:106.7±61.3,kaempferol intervention group:35.7±14.6,kaempferol intervention group compare with AHF model group,P<0.05;IL-6/HPRT normal control group:1.1±0.07,AHF model group:24.9±6.9,kaempferol intervention group:9.4±1.6,kaempferol intervention group compare with AHF model group,P<0.05.The expression of related molecules in NF-κB signaling pathway:IκB-α/β-actin:normal control group:0.24±0.05,AHF model group:0.07±0.01,kaempferol intervention group:0.26±0.014,kaempferol intervention group compare with AHF model group,P<0.05;p-NF-κBp65/β-actin:normal control group:0.10±0.03,AHF model group:0.21±0.03,kaempferol intervention group:0.11±0.02,kaempferol intervention group compare with AHF model group,P<0.05.)Conclusion:At the time of AHF,a large number of hepatocytes undergo inflammatory response and apoptosis,NF-κB signaling pathway is an important inflammatory pathway.Kaempferol can improve the survival rate of D-GalN/LPS-induced AHF mice and improve the liver function of mice,reduce the pathological damage of liver tissue and reduce the apoptosis of hepatocytes.Kaempferol can regulate the NF-κB signaling pathway to reduce the inflammatory response of the liver,so as to further improve the liver damage of AHF,to protect the liver.