Protective role and mechanism of dexmedetomidine on the LPS-stimulated PC12 cells / 解放军医学杂志

ABSTRACT

Objective To explore the effect ofdexmedetomidine on the lipopolysaccharide (LPS) stimulated PC12 cells and its potential mechanism.Methods PC12 cells were treated by LPS with a concentration of 400μg/ml.The cell viability,the concentrations ofinterleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) in the cell culture supernatant were measured after 3-,6-,or 12-h treatment.The expressions of toll-like receptor 4 (TLR4),myeloid differentiation factor 88 (MyD88) and phosphorylated p65 (p-p65) were measured.In the second part,PC12 cells were cultured under four different treatments,that is,normal culture media in first group,400μg/ml LPS in second group,100μmol/L dexmedetomidine in third group,400μg/ml LPS and100μmol/L dexmedetomidine in fourth group.The indexes mentioned above were measured 6 hours after LPS and DEX treatments.Results The cell viability was decreased after LPS treatment,and the concentrations of IL-6 and TNF-α were increased significantly.Compared with control group,the concentrations in 3-,6-,12-h groups showed statistically significant differences (P＜0.05),especially after 6 hours.The TLR4/MyD88/NF-κB pathway was activated after LPS stimuli and reached the peak value.Compared with LPS treatment group,PC 12 cell apoptosis rate,the concentrations of IL-6 and TNF-α and the expressions of TLR4,MyD88 and p-p65 were decreased.The differences between LPS+DEX group and LPS group was statistically significant (P＜0.05).Conclusion Dexmedetomidine has a protective effect on LPS stimulated PC 12 cells via the inhibition of inflammatory response.