Study on the Effect and Its Mechanism of Dexmedetomidine on the Inflammatory Response in Septic Mice
10.6039/j.issn.1001-0408.2017.19.17
- VernacularTitle:右美托咪定对脓毒症小鼠炎症反应的影响及机制研究
- Author:
Mao GUO
;
Wenming WANG
- Keywords:
Sepsis;
Dexmedetomidine;
miR-146a;
Inflammatory response;
Mice;
Toll-like receptor 4/nuclear factor-κB
- From:
China Pharmacy
2017;28(19):2651-2654
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To study the effect and its mechanism of dexmedetomidine(Dex)on inflammatory response in septic mice. METHODS:Mice were randomly divided into normal control group,model group,miR-146a inhibitor (50 mg/kg)+Dex (50 μg/kg)group,Dex low-dose,medium-dose,high-dose groups(10,30,50 μg/kg),10 in each group. Except for normal con-trol group,other groups were intraperitoneally injected lipopolysaccharide to induce septic models,intraperitoneally injected rele-vant medicines after 0.5 h. After drug intervention for 6 h,miR-146a expression,IRAK1 and TRAF6 mRNA expressions in periph-eral blood mononuclear cells in each group were detected by real-time fluorescence quantitative polymerase chain reaction method. IRAK1,TRAF6 protein expressions in peripheral blood mononuclear cells in each group were detected by Western blot method. TNF-α,IL-6 levels in serum were detected by enzyme-linked immunosorbent method. RESULTS:Compared with normal control group,miR-146a expression,TNF-α and IL-6 levels,IRAK1,TRAF6 mRNA and protein expressions in peripheral blood mononu-clear cells in model group were increased(P<0.01). Compared with model group,miR-146a expression in peripheral blood mono-nuclear cells in Dex medium-dose,high-dose groups were increased;TNF-α and IL-6 levels,IRAK1,TRAF6 protein expressions were decreased (P<0.05 or P<0.01);while IRAK1,TRAF6 mRNA expressions changed less obviously (P>0.05). Compared with Dex high-dose group,miR-146a expression,in peripheral blood mononuclear cells in miR-146a inhibitor+Dex group was de-creased;TNF-α and IL-6 levels,IRAK1,TRAF6 protein expressions were increased (P<0.05 or P<0.01);while IRAK1, TRAF6 mRNA expressions changed less obviously(P>0.05). CONCLUSIONS:Dex can inhibit the inflammatory response in sep-tic mice. The mechanism may associate with inducing miR-146a expression and inhibiting the 2 important adaptor proteins IRAK1, TRAF6 expressions in Toll-like receptor 4/nuclear factor-κB pathway.
