The Intervention Mechanism Of ω-3Polyunsaturated Fatty Acidon Inflammatory Injury Of Nonalcoholic Fatty Liver Disease

Purpose： Nonalcoholic fatt y liver diseaseis one of the most commo nchronic liver disease， it，s inflammatory react ion plays an important ro lethroughout the who le process o f the disease．In recent years， so me stud yfound that o mega-3polyunsaturat ed fatt y acids have a posit ive intervent ioneffect on NAFLD inflammatory injury， but the specific mechanism isunclear，so this paper will to discuss the possible mechanisms o f o mega-3PUFA alleviate NAFLD inflammatory injury．Methods：High fat feeding is adopted to establish an animal model o fNAFLD． Choose160～180g male SD rats， rando mly divided into4groups，each group have48s：normal feed group (CON group)，a high-fat(20%fat) feeding for NAFLD model group (HFD group)，based o n high fatfeedstuff add fish o il(10%lard+10%fish oil)for fish o il intervention group(FOH)，based on high fat feedstuff addPerilla oil (14.83%+5.17%Perillaoil)for Perilla oilintervent ion group (POH)， respectively in the experimentsof4w，8w，12w and16w point beheaded take blood to death，detect io nrelated indicators． The physio logical level including body weight， liverweight and liver index． I n serum biochemical level， we useenzymemethodto detect liver funct ion (ALT， AST) and blood lipids (TC， TG，HDL-C， LDL-C)， SOD， GST and NEFA changes.In pathological level；HE staining to observe hepatocellular ballooning change， the degree o fsteatosis degree and inflammatory reaction; Masson staining to observe theliver t issue fibrosis stage； Immunohistochemical techniques to detectmacrophages specific antibody CD68protein expressio n．In the mo lecularlevel， we use real-t ime fluorescent quantitat ive PCR to detect the livertissue IL-6， IL-1β， TNF， MCP-1， the NF-kB P65mRNA expressio nlevel． Results：(1)At8w, the HFD group rat liver index increasedsignificant ly， hepatocyte ballooning changed significant ly， hepatocytesteatosis， lobular and portal area have inflammatory cells infiltration，fibrosis obviously． Significant ly higher serum levels o f ALT， TCH，FFA， HDL-C significant ly lower． At12w， AST， TG， LDL-C alsosignificant ly increased，SOD significant ly lower，at16w，GST significantrise． Inflammatory cytokines (IL-6， IL-1β， TNF)， chemokine MCP-1mRNA expressio n are significant ly increased at8w， to the12wNF-kBP65mRNA expressio n is significant ly increase d． In protein levels， CD68posit ive expressio n significant ly increased， large gathering macrophagesat16w．(2)After the fish o il intervention， hepatocyte ballooning steatosis，lobular and portal area in inflammatory cells infiltrat ion and fibrosis havedifferent degrees of improvement． At4w serum ALT， TCH， FFAsignificant ly lower co mpare with HFD group； To8w LDL-C, GSTsignificant ly lower co mpare with HFD group；12w AST，TG significant lylower compare with HFD group，SOD significant ly increased．RNA level，inflammatory cytokines IL-6began to significant ly lower at4w，TNF in8w significant ly lower， IL-1β began to significant ly lower at12w；Chemokines MCP-1in8w significantly lower； The NF-kB P65significant ly lower at the beginning of the12w． Protein levels， CD68posit ive expressio n decreased significant ly at16w．(3)After the Perilla o il intervent ion，hepatocyte ballooning steatosis，lobular and portal area in inflammatory cells infiltrat ion， fibrosis alsopresents different degrees o f improvement. At4w serum ALT significant lylowerco mpare with HFD group； to8wTCH, LDL-C FFA， GST the HFDgroup significant ly lower co mpare with HFD group； to12w AST， T Gsignificant ly lower co mpare with HFD group， SOD the HFD group significant ly increased． RNA levels， inflammatory cytokines IL-6waslower but no significant change， at12w the TNF， IL-1β， ChemokinesMCP-1began to significant ly lower；The NF-kB P65significant ly lower atthe beginning o f the16w． Protein levels， CD68posit ive expressio ndecreased significant ly at16w．Conclusion：(1) A high-fat diet for8w，rat liver get to the progress o fNASH， intervent ion with fish o il， Perilla o il have different relieves thedegree of inflammatory reaction．(2) The omega-3PUFA may act ivat ing thenf-kappa B pathway， increase the production o f inflammatory cytokines，eventually led to the occurrence of nonalcoholic fatty hepat it is．...