ABSTRACT
Objective:To investigate whether memantine hydrochloride (MEM) could promote the bactericidal effect of neutrophils against methicillin-resistant Staphylococcus aureus (MRSA) and the possible mechanism. Methods:Neutrophils were co-incubated with different concentrations of MEM and MRSA for 4 h. Then the cell lysates were collected and cultured on plate for survival bacteria counting. After co-incubation, the neutrophils were collected to detect the production of reactive oxygen species (ROS) and the release of neutrophil extracellular traps (NETs). A mouse model of MRSA infection was established, and then the mice were treated with or without MEM. Blood, spleen and kidney samples were collected from the mice for bacterial colony counting and blood procalcitonin (PCT) detection. In the 48 h survival experiment, the mice were first infected with MRSA, and then treated with MEM or PBS. The survival rates of the mice were calculated and the survival curves were drawn.Results:The number of MRSA co-cultured with neutrophils decreased significantly in the presence of MEM, and within a certain concentration range, the survival number of MRSA decreased with the increase of MEM concentration. Moreover, MEM could significantly promote the production of ROS by neutrophils and the formation of NETs. In vivo experiment showed that the concentration of PCT in mouse blood samples was lower in the MRSA+ MEM group than in the MRSA+ PBS group. The animal experiment also revealed that MEM significantly decreased the bacteria loads in mouse blood and organs and increased the 48 h survival rate after MRSA infection.Conclusions:MEM could significantly promote the bactericidal effect of neutrophils against MRSA, which might be related to the enhanced generation of ROS by neutrophils and the formation of NETs.
ABSTRACT
Objective:To investigate the characteristics of serum cytokine IL-4 and IFN- γ levels in patients with chronic insomnia with mild cognitive impairment (MCI), and to further explore the relationship between cognitive function and IL-4 and IFN-γ in patients with chronic insomnia.Methods:Sixty-two patients with chronic insomnia were divided into MCI group( n=30) and non-MCI group( n=32) according to the scores of Montreal cognitive assessment(MoCA), mini-mental state examination(MMSE) score and chief complaint of cognitive decline. Pittsburgh sleep quality index(PSQI), Hamilton depression scale(HAMD 24) and Hamilton anxiety scale 14 item(HAMA 14) were evaluated. Serum IL-4 and IFN-γ were detected by flow fluorescence, correlation analysis and regression analysis were carried out. Results:The levels of IL-4 and IFN-γ in MCI group were significantly lower than those in non-MCI group (IL-4: 0.875(0.143, 1.655)μg/L, 1.855(0.813, 2.723)μg/L; IFN-γ: 0.450(0.173, 1.163)μg/L, 1.160(0.483, 3.075)μg/L, all P<0.05). There was no significant difference in IFN- γ/IL-4, PSQI, HAMA 14 and HAMD 24 scores between MCI group and non-MCI group. IL-4 was positively correlated with the total score of MoCA( r=0.318, P<0.05), orientation( r=0.324, P<0.05)and delayed recall( r=0.368, P<0.01). The results of multivariate regression showed that IL-4 had significant effects on MCI in patients with chronic insomnia( B=2.161, OR=8.682, 95% CI=2.058~36.633, P=0.003). Conclusion:The cognitive function of chronic insomnia is closely related to serum IL-4 and IFN-γ, and serum IL-4 has a protective effect on cognition in chronic insomnia patients. Therefore, it can be speculated that cytokines may be an important pathophysiological link of cognitive change in chronic insomnia patients.