Effects of Penehyclidine Hydrochloride Combined with Mechanical Ventilation on Inflammation in Rats with ARDS_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

YANG Zhou , SHEN Feng

Department of Critical Care Medicine, Affiliated Hospital of Guiyang Medical College. Guiyang, Guizhou,550004, ChinaCorresponding Author: SHEN Feng, E-mail: doctorshenfeng@ 163. com;

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Keywords：

Acute respiratory distress symdrom; Mechanical ventilation; Penehyclidine hydrochloride

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Objective To observe the effects of penehyclidine hydrochloride ( PHCD) combined with mechanical ventilation ( MV) on inflammatory response in rats with ARDS induced by oleic acid ( OA) .
Methods The rat ARDS model was established by OA via intravenous injection ( iv) . 32 adult healthy male SD rats were randomly divided into four groups, ie. a normal control group( group C: intra-peritoneal injection of a same amount of normal saline and intravenous injection of a same amount of normal saline respectively rather than PHCD) , a model group( group A1) , a PHCD group ( group A2: intra-peritoneal injection of 0. 5 mg/kg PHCD30 minutes before OA iv) and a PHCD+MV group ( group A3: VT = 4 mL/kg,respiratory rate =70 beats /min, I∶E =1∶2, FiO2 =21%) . Four hours after OA iv, arterial partial pressure of oxygen ( PaO2 ) was measured, and the oxygenation index ( PaO2 /FiO2 ) as well as wet /dry weight ratio( W/D) of lung tissue were calculated respectively. The pathological changes of lung tissue was observed through light microspcope. Interlukin-8 ( IL-8 ) , myeloperoxidase ( MPO) and NF-κB in lung tissue homogenate were measured by enzyme linked immunosorbent assay ( ELISA ) .
Results Extensive pneumonedema, pneumorrhagia, focal atelectasis and amout of inflammatory cells infiltration in lung tissues were all revealed in ARDS rats. Lung injury score ( 8. 63 ±2. 20 vs. 1. 38 ±0. 92) , W/D ratio ( 8. 37 ±0. 99 vs. 4. 08 ±0. 65) were all higher in the ARDS rats than those in group C( all P lt;0. 01) . PaO2 /FiO2 was lower in group A1 than that in group C [ ( 206 ±32) mm Hg vs. ( 428 ±28) mm Hg, P lt; 0. 01] . The concentrations of MPO [ ( 33. 91 ±1. 43) ng/mL vs. ( 20. 92 ±1. 40) ng/mL) ] , IL-8 [ ( 809 ±39) ng/L vs. ( 583 ±91) ng/L] and NF-κB [ ( 1163 ±105) ng/L vs. ( 803 ±130) ng/L] in lung tissue homogenate were significantly increased in the ARDS rats than those in group C ( all P lt;0. 01) . Pathological changes of lung tissue ( including pneumonedema, pneumorrhagia, atelectasis and inflammatory cell infiltration, etc. )obviously improved when treated by PHCD or/and PHCD combined with MV ( all P lt;0. 05) . PaO2 /FiO2 in group A2 and A3 were both significantly increased when compared with group A1 ( both P lt; 0. 05) .Meanwhile,W/D ratio, lung injury score, and concentrations of MOP, IL-8 and NF-κB were sharply decreased in group A2 and A3 ( all P lt;0. 05) . The improvement in all above indices were more significant in group A3 than those in group A2, despite all those indices failed to meet the levels of normal rats ( all P lt; 0. 05) .
Conclusion PHCD can inhibit the inflammatory response in ARDS rats induced by OA iv, through which it protect the lung tissue frominjury induced by OA. The protective role of PHCD plus MV is superior to that of PHCD only.

Citation： YANG Zhou,SHEN Feng. Effects of Penehyclidine Hydrochloride Combined with Mechanical Ventilation on Inflammation in Rats with ARDS. Chinese Journal of Respiratory and Critical Care Medicine, 2013, 12(5): 485-488. doi: Copy

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1. 芮萌, 段蕴铀. 中性粒细胞凋亡与急性肺损伤. 中国急救医学,2008, 28: 1129-1132.
2. 姜丽华, 王涛, 姚尚龙. 盐酸戊乙奎醚预先给药对新生大鼠内毒素性急性肺损伤时NF-κB 活性的影响. 中华麻醉学杂志, 2010 ,30: 369 -371.
3. 雷利荣, 王焱林, 贾宝辉, 等. 盐酸戊乙奎醚对腹腔感染脓毒症小鼠肺损伤的保护作用. 中国危重病急救医学, 2007 , 19 : 623-624.
4. 王棣馨, 但伶. 盐酸戊乙奎醚预先给药对失血性休克大鼠急性肺损伤时NF-κB 活性的影响. 中华麻醉学杂志, 2010, 30 : 497-499.
5. 唐召力, 许健瑞, 梁丽萍. 油酸制造急性呼吸窘迫综合征动物模型. 实用心脑血管病杂志, 2005 , 13: 235-236.
6. 王全红, 沈锋. 不同水平呼气末正压通气对急性肺损伤/急性呼吸窘迫综合症大鼠水通道蛋白1 和5 的影响. 中华结核和呼吸杂志, 2012, 35 : 706-707.
7. Smith KM, Mrozek JD, Simonton SC, et al. Prolonged partial liquid ventilation using conventional and high-frequency ventilatory techniques: Gas exchange and lung pathology in an animal model ofrespiratory distress syndrome. Crit Care Med, 1997 , 25: 1888 -1897.
8. 陈文杰, 沈锋, 王迪芬. 大鼠急性肺损伤肺组织中白细胞介素17的含量变化及异丙酚的影响. 中国呼吸与危重监护杂志, 2010 ,9 : 532-536.
9. 俞辰斌, 孙海晨, 聂时南, 等. 盐酸戊乙奎醚对创伤性急性肺损伤的早期干预作用. 创伤外科杂志, 2007, 9: 359-362.

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Effects of Penehyclidine Hydrochloride Combined with Mechanical Ventilation on Inflammation in Rats with ARDS

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