Impact Assessment From Targeted-regulating Of Notch-1/NF-?B Signaling Pathway On The Sepsis Encephalopathy

Objective:The levels of various inflammatory mediators,as well as the changes of Notch-1,NF-?B mRNA and protein expression in the brain tissues of sepsis mice were detected.A mouse model of sepsis-associated encephalopathy was established by overexpressing lentivirus miR-34a to evaluate the role of miR-34a in regulating the signaling pathway of Notch-1/NF-KB in sepsis-associated encephalopathy mice.Methods:A total of 54 mouses of clean grade were divided randomly(random number)into four groups,sham group,n=9,only sham-operated laparotomy and abdominal suturing was performed;NC group,n=15,intrathecal negative control lentivirus 5ul(concentration 5×109),one time per day,3days,CLP was performed on the seventh day;Operated group(CLP group),n=15,peritoneotomy,the cecum ligation operation(CLP)and abdominal suturing was performed;intervention group,intrathecal miR-34a lentivirus 5ul(concentration 5×109),one time per day,3 days,CLP was performed on the seventh day.During the observed behavioral changes in mice and assess neurological scores 24 h after CLP.Four group were sacrificed 24 h after modeling or operation.The brain tissues were taken.Pathological changes of brain tissues were observed by light microscopy.The levels of IL-1? IL-6,IL-10 and TNF-a in the brain were measured by ELISA method.The mRNA and protein expression of NF-?B mRNA and Notch-1 in the brain were measured by real-time PCR and Western blot methods.Results:The neurological scores,the cerebral IL-1? and TNF-a levels,and the protein expression of NF-?B(p<0.01),and IL-6(p<0.05)in NC group modeling after 24 h obvious increased than that in sham group.The cerebral IL-10 level,the mRNA and protein expression of Notchl in NC group modeling after 24 h obvious decreased than that in sham group.The mRNA expression of NF-?B had no significant difference in NC group compared with sham group(p>0.05).The neurological scores,the cerebral IL-6,TNF-? levels,the mRNA and protein expression of NF-?B(p<0.01),and IL-1?levels(p<0.05)in CLP group modeling after 24 h obvious increased than that in sham group.The cerebral IL-10 level and the mRNA and protein expression of Notch-1(p<0.01)in CLP group modeling after 24 h obvious decreased than that in sham group.The IL-10 level(p<0.05)and the mRNA(p<0.05)and protein expression(p<0.01)of Notchl in intervention group modeling after 24 h obvious increased than that in CLP group.The mRNA(p<0.05)and protein expression(p<0.01)of NF-?B and the cerebral TNF-a(p<0.01)levels in intervention group modeling after 24 h obvious decreased than that in CLP group.The neurological scores,IL-6 and IL-1?levels had no significant difference in intervention group compared with CLP group(p>0.05).Each indicator in NC group had no significant difference compared with CLP group(p>0.05).After 24h after operation,the degree of cerebral damage were also decreased in intervention group compared withNC group and CLP group in the lightmicroscope.Conclusions:Targeted-regulating of Notch-1/NF-?B signaling pathway can be partially mitigated sepsis encephalopathy brain damage.