【摘要】 目的评价大鼠肉瘤基因同源物（Rho）/Rho相关卷曲螺旋蛋白激酶（Rock）信号通路在呼吸机相关性肺损伤（VILI）中的作用,以及法舒地尔对VILI的保护作用。方法选取2019年1—5月在南昌大学第二附属医院行择期全身麻醉下机械通气时间≥4 h的普通外科手术患者60例,采用随机数字表法将患者分为法舒地尔组和0.9%氯化钠组（对照组）,每组30例。法舒地尔组于麻醉诱导后给予法舒地尔30 mg（以100 mL 0.9%氯化钠溶液稀释）静脉注射,于15 min内完成;对照组给予等容量0.9%氯化钠溶液静脉注射。记录两组患者手术过程中呼吸机参数（潮气量、峰流速、呼吸频率、PEEP）,分别于麻醉诱导前和麻醉苏醒后进行急性生理学与慢性健康状况评价Ⅱ（APACHEⅡ）评分,分别于机械通气前后采集患者的外周血和动脉血样本,测定血清Rock水平并行血气分析（血气分析指标为p_aO₂、氧合指数、呼吸指数）。分别于机械通气前后收集患者的支气管肺泡灌洗液（BALF）,采用ELISA法测定BALF中髓过氧化物酶（MPO）、TNF-α、IL-6、RhoA和Rock2水平。记录两组患者术后7 d肺部并发症的发生情况。结果两组间患者手术过程中潮气量、峰流速、呼吸频率和PEEP的差异均无统计学意义（P值均>0.05）。两组间麻醉诱导前APACHEⅡ评分的差异无统计学意义（P>0.05）,法舒地尔组麻醉苏醒后APACHEⅡ评分显著高于对照组麻醉苏醒后（P<0.05）。两组间机械通气前血清Rock水平和氧合指数、呼吸指数、p_aO₂,以及BALF中MPO、TNF-α、IL-6、RhoA和Rock2水平的差异均无统计学意义（P值均>0.05）。法舒地尔组机械通气后氧合指数显著高于对照组机械通气后（P<0.05）,血清Rock水平和呼吸指数均显著低于对照组机械通气后（P值均<0.05）;两组间机械通气后p_aO₂的差异无统计学意义（P>0.05）。法舒地尔组机械通气后BALF中MPO、TNF-a、IL-6、RhoA和Rock2水平均显著低于对照组机械通气后（P值均<0.05）。法舒地尔组术后7 d肺部并发症发生率显著低于对照组（P<0.05）。结论 Rock抑制剂法舒地尔可减轻患者机械通气时VILI,减少术后肺部并发症的发生,该作用机制可能与其抑制Rho/Rock信号通路后减轻炎症反应有关。更多还原

【Abstract】 Objective To evaluate the role of the rat sarcoma homolog（Rho）/Rho associated coiled-coil forming protein kinase（Rock） signaling pathway in ventilator-induced lung injury（VILI） and the protective role of fasudil. Methods Sixty patients, who underwent elective general surgery under mechanical ventilation for more than 4 hours in our hospital from January 2019 to May 2019, were selected and randomly divided into fasudil group and control group（n=30）. Fasudil 30 mg（diluted with 100 mL 0.9% sodium chloride solution） was intravenously injected within 15 min after induction of anesthesia in fasudil group. The equal volume of saline was given in control group. The respiratory function indexes（tidal volume, peak flow rate, respiratory rate and positive end expiratory pressure [PEEP]） during operation were recorded in the two groups. Acute physiology and chronic health evaluation Ⅱ（APACHE Ⅱ） scores were recorded before anesthesia induction and after anesthesia recovery. The samples of peripheral blood and arterial blood and the alveolar lavage fluid were collected before and after mechanical ventilation. Serum Rho kinase levels, p_aO₂, oxygenation index and respiratory index were measured. Myelinated peroxidase（MPO）, tumor necrosis factor-α（TNF-α）, interleukin-6（IL-6）, RhoA and Rock2 in bronchoalveolar lavage fluid were measured by enzyme linked immunosorbent assay（ELISA）. The incidence of pulmonary complications was recorded within 7 days after surgery. Results There was no significant difference in tidal volume, peak flow rate, respiratory frequency, or PEEP between the two groups（all P>0.05）. Neither was the APACHE Ⅱ score before anesthesia induction（P>0.05）. The APACHE Ⅱ score after anesthesia recovery in fasudil group was significantly higher than that in control group（P<0.05）. There was no significant difference in Rock, oxygenation index, respiratory index, p_aO₂, MPO, TNF-α, IL-6, RhoA or Rock2 before mechanical ventilation between the two groups（all P>0.05）. Compared with control group, after mechanical ventilation, the oxygenation index was significantly increased in fasudil group, while the level of serum Rho kinase, respiratory index and the levels of MPO, TNF-α, IL-6, RhoA and Rock2 in alveolar lavage fluid were significantly decreased（all P<0.05）. No significant difference was found in p_aO₂ between the two groups after mechanical ventilation（P>0.05）. The incidence of postoperative pulmonary complications in fasudil group was significantly lower than that in control group（P<0.05）. Conclusion Fasudil can alleviate VILI and reduce the incidence of postoperative pulmonary complications, which may be related to the reduction of inflammatory response after inhibition of Rho/Rock signaling pathway.更多还原