Protective effects of miR-34a on brain function of mice with sepsis by regulating Notch-1/NF-κB signaling pathway

Objective To observe the dynamic changes of TNF-α, IL-1β, IL-6, IL-10, and expressions of Notch-1, NF-κB mRNA and their protein levels in the brain tissue of septic mice and intervention effects of intrathecal injection of lentiviral vector of miR-34a gene for regulating Notch-1/NF-κB signaling pathway. Methods A total of 54 mice of clean grade were divided randomly(random number)into four groups, namely sham group(n=9), in which sham-operated laparotomy was performed; CLP group(n=15), in which the cecum ligation operation(CLP) was performed; NC group(n=15), in which intrathecal injection of lentivirus 5 μL(concentration 5×108 TU/mL), one time per day, for 3 days, then CLP was performed on the seventh day; intervention group(n=15), in wihch intrathecal injection of miR-34a lentivirus 5 μL(concentration 5×108 TU/mL), one time per day, for 3 days, then CLP was performed on the seventh day. The mice of four groups were sacrificed 24 h after modeling or operation. The changes of behavior of mice was observed and the neurological scores were assessed 24 h after CLP. The levels of TNF-α, IL-1β, IL-6 and IL-10 in the brain were measured by ELISA method. The mRNA expression and protein levels of Notch-1 and NF-κB in the brain tissue were measured by real-time PCR and Western blot method, respectively. Pathological changes of brain tissue were observed under light microscope. Results The neurological scores, the cerebral TNF-α, IL-6 levels, the mRNA expression and protein level of NF-κB(P 0.05). The IL-10 level (P 0.05). The degree of cerebral damage found under light microscope was also ameliorated in intervention group compared with CLP group 24 h after modeling. Conclusions The effects of miR-34a via regulating Notch-1/NF-κB signaling pathway on brain function exerts cerebral protective effects in septic mice. Key words: miR-34a; Notch-1; NF-κB; Lentiviral vector; Mice