Effect of BML-111 on ventilator-induced lung injury in rats
10.3760/cma.j.issn.0254-1416.2015.12.022
- VernacularTitle:BML-111对大鼠机械通气诱发肺损伤的影响
- Author:
Hongbin LI
;
Zhouyang WU
;
Guangzhi WANG
;
Jie GONG
;
You SHANG
;
Shanglong YAO
- Publication Type:Journal Article
- Keywords:
Receptors,lipoxin;
Respiration,artificial;
Respiratory distress syndrome,adult
- From:
Chinese Journal of Anesthesiology
2015;(12):1487-1490
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the effect of BML?111 on ventilator?induced lung injury in rats. Methods Forty?eight healthy male Sprague?Dawley rats, weighing 200-250 g, aged 6-8 weeks, were randomized into 6 groups ( n=8 each) using a random number table: control group ( C group) , low tidal volume (VT) group (LVTgroup), high VT group (HVTgroup), low dose BML?111 group (BL group), high dose BML?111 group ( BH group) , and BML?111 plus BOC?2 ( lipoxin A4 receptor antagonist) group ( BOC?2 group) . Group C kept spontaneous breathing after tracheotomy, and received no mechanical venti?lation. The rats in the other 5 groups were mechanically ventilated ( respiratory rate 80 breaths∕min, frac? tion of inspired oxygen 21%, positive end?expiratory pressure 0) . The VT was 6 ml∕kg in group LVT , or 20 ml∕kg in HVT, BL, BH and BOC?2 groups. BML?111 0?1 and 1?0 mg∕kg were injected intraperitoneally during ventilation in BL and BH groups, respectively. In group BOC?2, BOC?2 50 μg∕kg was injected in?traperitoneally before ventilation, and BML?111 1?0 mg∕kg was injected intraperitoneally during ventilation. Arterial blood samples were collected at 4 h of ventilation, arterial oxygen partial pressure ( PaO2 ) was de?termined. Then animals were sacrificed by exsanguination. Bronchoalveolar lavage fluid ( BALF) of the left lung was collected for determination of neutrophil count, and the level of neutrophil was calculated. The right lung tissue specimens were obtained for microscopic examination, and for determination of wet∕dry lung weight ratio ( W∕D ratio ) , myeloperoxidase ( MPO ) activity, and contents of malondialdehyde ( MDA) , monocyte chemoattractant protein?1 ( MCP?1) , tumor necrosis factor?alpha ( TNF?α) , interleu?kin?1beta ( IL?1β) and IL?6. Results Compared with group C, PaO2 was significantly decreased, and the level of neutrophil in BALF, W∕D ratio, MPO activity, and contents of MDA, MCP?1, TNF?α, IL?1β and IL?6 were increased in group HVT ( P<0?05) , and no significant change was found in the variables mentioned above in group LVT ( P>0?05) . Compared with group HVT , PaO2 was significantly increased, and the level of neutrophil in BALF, W∕D ratio, MPO activity, and contents of MDA, MCP?1, TNF?α, IL?1β and IL?6 were decreased in group BH, and the contents of TNF?α, IL?1βand IL?6 were significantly decreased ( P<0?05) , and no significant change was found in the other variables in group BL ( P>0?05) . Compared with group BH, PaO2 was significantly decreased, and the level of neutrophil in BALF, W∕D ratio, MPO activity, and contents of MDA, MCP?1, TNF?α, IL?1β and IL?6 were increased in group BOC?2 (P<0?05). The pathological changes were significantly attenuated in group BL as compared with HVT and BOC?2 groups. Conclusion BML?111 can attenuate ventilator?induced lung injury in rats, and activated lipoxin A4 receptors are involved in the mechanism.
