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.%目的：观察戊乙奎醚联合机械通气对大鼠盐酸吸入性急性呼吸窘迫综合征（ARDS）炎症反应的影响。方法将32只成年健康雄性SD大鼠按简单随机法分为假手术组、ARDS模型组、戊乙奎醚组（盐酸吸入前30 min经腹腔注入戊乙奎醚0.5 mg/kg）及机械通气组〔在戊乙奎醚预处理后给予机械通气，呼吸机参数设置：潮气量（VT）4 mL/kg、呼吸频率（RR）70次/min、吸呼比（I：E）1：2、吸入氧浓度（FiO2）0.21〕4组，每组8只。气管内滴注盐酸（0.1 mol/L，1.2 mL/kg）方法复制大鼠ARDS模型。机械通气4 h后为实验终点。测定大鼠动脉血氧分压（PaO2）并计算氧合指数、肺湿/干重（W/D）比值；光镜下观察肺组织病理学改变，并计算病理评分；用酶联免疫吸附试验（ELISA）测定肺组织匀浆中髓过氧化物酶（MPO）、白细胞介素-8（IL-8）及核转录因子-κB（NF-κB）含量。结果模型组大鼠肺组织中有明显炎性细胞浸润，广泛肺泡塌陷，透明膜形成，而肺间质水肿及肺微血管充血不明显。与假手术组比较，模型组大鼠肺组织病理评分（分：9.88±2.03比1.38±0.92）、肺W/D比值（7.67±0.96比4.08±0.65）均明显升高（均P＜0.01），氧合指数〔mmHg（1 mmHg＝0.133 kPa）：213±29比428±28）明显降低（P＜0.01）；肺组织匀浆中MPO（μg/L：34.18±3.99比20.92±1.40）、IL-8（ng/L：864±53比583±91）、NF-κB（ng/L：1229±133比803±130）均高于假手术组（均P＜0.01）。戊乙奎醚组、机械通气组炎性细胞浸润、肺泡塌陷等改变均较模型组减轻，肺组织病理评分、肺W/D比值均较模型组明显降低，氧合指数明显升高，肺组织MPO、IL-8、NF-κB均低于模型组（均P＜0.05）；以机械通气组改变较戊乙奎醚组更为明显（肺组织病理评分：5.63±1.85比7.63±1.67，肺W/D比值：5.35±1.05比6.46±1.17，氧合指数：325±57比272±44，MPO：25.80±3.36比29.88±3.93，IL-8：736±53比802±53，NF-κB：984±75比1109±118，均P＜0.05），但均未达到假手术组水平（P＜0.05或P＜0.01）。结论戊乙奎醚能减轻盐酸吸入性ARDS大鼠肺组织炎症反应，戊乙奎醚联合机械通气的作用优于戊乙奎醚单独使用；抑制肺组织炎症反应可能是戊乙奎醚联合机械通气对盐酸吸入性ARDS大鼠实施保护作用的机制之一。
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