Effect of penehyclidine hydrochloride combined with mechanical ventilation on inflammation in rats with acute respiratory distress syndrome induced by hydrochloric acid inhalation
10.3969/j.issn.1008-9691.2014.01.015
- VernacularTitle:戊乙奎醚联合机械通气对盐酸吸入性急性呼吸窘迫综合征大鼠炎症反应的影响
- Author:
Zhou YANG
;
Feng SHEN
- Publication Type:Journal Article
- Keywords:
Penehyclidine hydrochloride;
Mechanical ventilation;
Hydrochloric acid;
Inhalation;
Acute respiratory distress syndrome;
Rat
- From:
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care
2014;(1):50-54
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the effect of penehyclidine hydrochloride (PHCD) combined with mechanical ventilation on inflammatory response in rats with acute respiratory distress syndrome(ARDS)induced by hydrochloric acid(HCl)inhalation. Methods 32 adult healthy male Sprague-Dawley(SD)rats were randomly divided into four groups:sham operation group,ARDS model group,PHCD group(intraperitoneal injection of 0.5 mg/kg PHCD at 30 minutes before HCl instillation)and mechanical ventilation group〔mechanical ventilation was given after PHCD treatment,ventilator settings were as follows:tidal volume(VT)=4 mL/kg,respiratory rate(RR)= 70 beats/min,the time ratio of inspiration to expiration(I:E)=1:2,fraction of inspired oxygen concentration(FiO2)=0.21〕,8 rats in each group. The rat ARDS model was created by HCl(0.1 mol/L,1.2 mL/kg) intratracheal instillation. After mechanical ventilation for 4 hours,the experiment was stopped. Arterial partial pressure of oxygen(PaO2)was measured,and the oxygenation index as well as lung wet/dry weight ratio(W/D)were calculated respectively. The pathological changes in lung tissues were observed under light microscope,and the pathological score was evaluated. The levels of myeloperoxidase(MPO),interlukin-8(IL-8)and nuclear factor-κB (NF-κB)in homogenate of lung tissues were all measured respectively by enzyme linked immunosorbent assay (ELISA). Results In rats of ARDS model group, there were significant infiltration of inflammatory cells, collapse of extensive pulmonary alveoli and hyaline membrane formation in lung tissues,but the edema in pulmonary mesenchymal tissue and congestion of micro vessels were not obvious. Compared with sham operation group,the lung tissue pathological score(9.88±2.03 vs. 1.38±0.92),lung W/D ratio(7.67±0.96 vs. 4.08±0.65)were significantly increased(both P<0.01),while oxygenation index〔mmHg(1 mmHg=0.133 kPa):213±29 vs. 428±28〕was markedly decreased in model group(P<0.01);and the concentrations of MPO(μg/L:34.18±3.99 vs. 20.92±1.40), IL-8(ng/L:864±53 vs. 583±91)and NF-κB(ng/L:1 229±133 vs. 803±130)in homogenate of lung tissues were significantly higher in model group(all P<0.01). The pathological changes in lung tissues including inflammatory cell infiltration,collapse of alveoli and pulmonary edema,etc. were obviously improved when treated by PHCD or mechanical ventilation and the lung pathological score and W/D ratio were significantly decreased compared with those of model group,oxygenation index in these two groups were both significantly increased,meanwhile, the concentrations of MPO,IL-8 and NF-κB were sharply decreased when compared with those of model group (all P<0.05). The degree of improvement in all above indexes were greater in mechanical ventilation group than those in PHCD group(lung injury score:5.63±1.85 vs. 7.63±1.67,lung W/D ratio:5.35±1.05 vs. 6.46±1.17, oxygenation index:325±57 vs. 272±44,MPO:25.80±3.36 vs. 29.88±3.93,IL-8:736±53 vs. 802±53, NF-κB:984±75 vs. 1 109±118,all P<0.05),however they did not reach the levels of the sham operation group (P<0.05 or P<0.01). Conclusion PHCD can inhibit the inflammatory response in ARDS rats induced by HCl inhalation,thus it may protect the lung tissue from injury induced by HCl,and the protective role of PHCD plus menchanical ventilation is superior to that of PHCD only.
