钙蛋白酶抑制剂在深低温停循环中肺保护机制的实验研究  

Calpain inhibitor LLY-FMK improves pulmonary function in deep hypothermic circulatory arrest cardiapulmonary bypass

作　　者：董莉亚[1] 张韫佼[1] 黄雅筠 许喜乐 Dong Li-ya Zhang Yun-jiao Huang Ya-jun Xu Xi-le(Departmen of Thoracic and Cardiovascular Surgery, Shanghai Xinhua Hospital, Shanghai Jiaotong University, School of medicine, Shanghai 200092, Chin)

机构地区：[1]上海交通大学医学院附属新华医院心胸外科,上海200092

出　　处：《中国体外循环杂志》2017年第3期185-189,共5页Chinese Journal of Extracorporeal Circulation

摘　　要：目的评估钙蛋白酶(calpain)抑制剂对心脏手术深低温停循环(DHCA)中炎症反应性肺损伤的保护机制,并探讨其作用是否通过核转录因子kappa B(NF-κB)介导。方法 16只幼猪建立体外循环(CPB)DHCA模型,随机分为对照组和实验组,实验组CPB前1 h静脉注射calpain抑制剂LLY-FMK(苄氧羧基-亮氨酸-亮氨酸-酪氨酸-荧光甲基酮)1 mg/kg,对照组则注射同剂量的生理盐水。检测两组CPB前和CPB/DHCA后肺静态顺应性、肺血管阻力指数、肺湿干质量比、支气管肺泡灌洗液肿瘤坏死因子-α(TNF-α)浓度以及肺组织NF-κB水平;CPB/DHCA结束取肺组织HE染色光镜观察肺组织水肿和炎细胞浸润情况。结果与CPB前相比,CPB后两组的肺静态顺应性下降,肺血管阻力、肺湿干重比和肺组织NF-κB表达增加(P<0.05),但两组相比,实验组的改变显著轻于对照组(P<0.05),实验组支气管肺泡灌注液中的TNF-α含量显著低于对照组(P<0.05),光镜下中性粒细胞渗出、肺水肿和肺泡损伤程度轻于对照组。结论 calpain抑制剂LLY-FMK能减轻DHCA后肺部炎症反应,从而改善肺功能,这种保护作用可能与降低NF-κB活性有关。Objective To evaluate the lung protective effects of calpain inhibitor in deep hypothermic circulatory arrest （DHCA）,especially the inflammatory lung injury,and investigate whether its effect is mediated by NF-κB.Methods Using an animal model of DHCA,16 piglets were divided randomly into two groups：control group and experimental group.Eight animals of experimental group were administered calpain inhibitor LLY-FMK （carbobenzoxy-leucinyl-leucinyl-tyrosine-fluoromethyl ketone） （1 mg/kg,intravenously） 60 mins before cardiopulmonary bypass,the other animals were administered saline as a control.At the beginning and end of CPB,lung static compliance （Cstat）,pulmonary vascular resistance （PVR）,TNF-α concentration of bronchoalveolar lavage fluid,NF-κB expressions of lung tissue and the lung wet/dry weight ratio （W/D） were measured.At the end of CPB,some lung tissues were fixed to observe pathological changes.Results After cardiopulmonary bypass,the Cstat decreased while,the PVR,the W/D,the NF-κB expressions of lung tissue increased in both groups,changes of experimental group were much less than those of control group.Content of TNF-α of bronchoalveolar lavage fluid in experimenatal group was lower than that in control group at the end of CPB,Infiltration of neutrophils,pulmonary edema and alveolar damage in experimental group decreased significantly compared with control group.Conclusion Calpain inhibitor can alleviate lung inflammatory response and improve lung function after DHCA,the improvement may be associated with the reduction of NF-κB activity.

关 键 词：体外循环 深低温停循环 CALPAIN 肺缺血再灌注损伤 

分 类 号：R654.1[医药卫生—外科学]