Impact of dexmedetomidine on p38MAPK signaling pathway in of ventilator -associated lung injury of rats
10.3760/cma.j.issn.1008-6706.2016.21.002
- VernacularTitle:右美托咪定对大鼠呼吸机相关肺损伤时 p38丝裂原活化蛋白激酶信号通路的影响
- Author:
Min QU
- Publication Type:Journal Article
- Keywords:
Ventilator -induced lung injury;
Dexmedetomidine;
p38 Mitogen -activated protein kinases;
Rats
- From:
Chinese Journal of Primary Medicine and Pharmacy
2016;23(21):3205-3209
- CountryChina
- Language:Chinese
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Abstract:
Objective To evaluate the effect of dexmedetomidine on p38 mitogen -activated protein kinase (p38MAPK)signaling pathways in ventilator -induced lung injury of rats.Methods 100 SD rats were divided into 5 groups(n =20)by random number table.The control group(Group C),mechanical ventilation(Group H)and different dosage of dexmedetomidine group (Group DEX1 -3 ).Group C:no mechanical ventilation with natural breathing air for 4h;Group H:high tidal volume ventilation for 4H,inhaled oxygen concentration was 21%;Group DEX1 -3:20min before mechanical ventilation,infusion of dexmedetomidine(0.5,1.0,and 2.0μg/kg)with loading dose (5mL,0.5,1.0,and 2.0μg·kg -1 ·h -1 )for 4 hours.Femoral arterial blood were collected after mechanical ventilation for 1h,2h and 4h(T1 -4 )in basic status,the arterial blood gas and the PaO2 were analysized and recorded. concentration of total protein,TNF -αand macrophage inflammatory protein -2(MIP -2)in bronchoalveolarlavage fluid(BALF)were detected in rats after ventilation for 4h;myeloperoxidase(MPO)activity in lung tissue was deter-mined;intercellular adhesion molecule -1(ICAM-1)expression and lung wet/dry weight(w/d)ratio were detected;p -p38MAPK protein expression was detected by Western blot;pathological changes of lung tissue in each group and cell apoptosis were observated.Results Compared with the group C,expression of P -p38MAPK(5.4 ±0.5)and p38MAPK/p -p38MAPK(1.64 ±0.17)increased in Group H(F =3.22,3.28,all P <0.05),accompanied by the increased expression of CAM-1 in lung tissue,MPO activity,total protein,TNF -αand MIP -2 concentration in the BALF[(6.4 ±1.1),(1.95 ±0.16)U /g,(1 459.39 ±0.29)mg/L,(182 ±9)ng/L,(436 ±31)ng/L](F =3.53, 3.66,3.21,3.32,3.43,all P <0.05);.And compared with group H,expression of p -p38MAPK and p38MAPK/p -p38MAPK in DEX2 groups and DEX3 fell(F =3.22,3.28,all P <0.05)accompanied by decreased expression of CAM-1 in lung tissue,MPO activity,total protein,TNF -a and MIP -2 concentration in the BALF(F =3.53,3.66, 3.21,3.32,3.43,all P <0.05).Compared with the group H,PaO2 at each point showed no statistically significant difference in group DEX1 -3(F =1.43,P >0.05),and no significant difference of W/D in group DEX 2 ~3(F =2.89,P >0.05 ).Heavy pathological damage of lung tissue and significant apoptosis were observed in group H. Conclusion Dexmedetomidine can inhibit the development of ventilator -associated lung injury.The mechanism may associated with the inhibition of phosphorylation of p38MAPK,thereby inhibiting the expression of downstream inflam-matory factors.
