孟鲁司特钠对大鼠肺缺血再灌注损伤的保护作用的研究  

Protective effects of montelukast on lung ischemia-reperfusion injury in rats

作　　者：陈良 白宏晔 甘辉立[1] CHEN Liang;BAI Hongye;GAN Huili(Department of Cardiac Surgery,Beijing Anzhen Hospital,Capital Medical University,Beijing Institute of Heart,Lung and Blood Vessel Diseases,Beijing 100029,China)

机构地区：[1]首都医科大学附属北京安贞医院-北京市心肺血管疾病研究所心脏外科,100029

出　　处：《心肺血管病杂志》2020年第6期728-732,共5页Journal of Cardiovascular and Pulmonary Diseases

基　　金：北京市自然科学基金项目(#7172067)。

摘　　要：目的:验证孟鲁司特钠(montelukast)对大鼠肺缺血再灌注损伤(LIRI)的预防作用。方法:将40大鼠随机分四组,每组10只:A组为假手术组、B组为LIRI模型组、C组为孟鲁司特钠低剂量组(ML组)、D组为孟鲁司特钠高剂量组(MH组)。A、B组连续4 d,每日接受2 mL/kg 0.9%氯化钠溶液灌胃,C、D:连续4 d,分别给予3 mg/kg、30 mg/kg孟鲁司特钠灌胃,溶剂为0.9%氯化钠溶液2 mL/kg。第5日,A组在相同的时间内仅接受麻醉下气管切开机械通气、开胸翻动、依次关胸,不进行缺血再灌注处理;其余三组:采用左肺动脉夹闭法制备大鼠肺缺血再灌注模型。造模后2 h断颈处死大鼠,结扎左肺门并切除左肺。测定肺组织干湿重比(W/D),HE染色观察肺组织病理变化;测定丙二醛(MDA)含量、髓过氧化物酶(MPO)活性、超氧化物岐化酶活以及核因子-κB(NF-κB)含量。结果:与假手术组对比,肺组织W/D、MDA、NF-κB含量及MPO、SOD活性,以及肺组织病理改变在LIRI模型组、ML组和MH组均有明显变化,差异有统计学意义(P<0.05);且ML组和MH组间的差异也具有统计学意义,且MH组病理改变更轻。结论:孟鲁司特钠可下调NF-κB蛋白表达,抑制炎性反应和氧化应激,来减轻大鼠肺缺血再灌注造成的肺损伤,且高浓度(30 mg/kg)较低浓度(10 mg/kg)保护作用更显著。Objective:To assess the protective effect of montelukast against lung ischemia-reperfusion injury(LIRI).Methods:Forty adult Sprague Dawley rats were randomly assigned to four groups of ten:sham group(group A),LIRI group(group B),montelukast low(ML)group(group C)and montelukast high(MH)group(group D).In group A and B,rats were i.g.normal saline 2 mL·kg^-1·d^-1 from day 1 to day 4.In group C and D,rats were i.g.normal saline 2 mL·kg^-1·d^-1 and montelukast 3 and 30 mg·kg^-1·d^-1 respectively from day 1 to day 4.In day 5,group A:only exposed left pulmonary artery;group B,C and D:clamped the left pulmonary artery 60 min followed by 120 min reperfusion.Then they were sacrificed and the lung tissues were taken for observation of the pathological changes and for measurement of the lung wet/dry weight ratio(W/D).the MDA,the activity of SOD and MPO in the lung tissue were determined;the expression of NF-κB in the lung tissue was determined by Western Blot.Results:Montelukast can effectively alleviate the lung damage caused by lung ischemia-reperfusion through down-regulating NF-κB expression,relieving inflammatory reaction and oxidative stress in rates.Conclusions:Montelukast can effectively alleviate the tissue damage caused by lung ischemia-reperfusion,which can reduce NF-κB expression and relieve inflammatory reaction and oxidative stress in rats.What’s more,High-dose montelukast(30 mg/kg)benefits the alleviation more than low-dose montelukast(10 mg/kg)does.

关 键 词：再灌注损伤 肺 孟鲁司特钠 大鼠 

分 类 号：R54[医药卫生—心血管疾病]