利多卡因抑制基质金属蛋白酶活性改善脂多糖诱导的小鼠急性肺损伤的机制研究  

Lidocaine attenuates LPS-induced acute lung injury in mice via an inhibition on matrix metalloproteinases

作　　者：郑彬彬 张嘉男 范轶鑫 胡亮[1] 刘文涛 王雪融[1] ZHENG Binbin;ZHANG Jianan;FAN Yixin;HU Liang;LIU Wentao;WANG Xuerong(School of Basic Medical Sciences,Nanjing Medical University,Nanjing 210029,China)

机构地区：[1]南京医科大学基础医学院,南京210029

出　　处：《中国药科大学学报》2020年第2期180-184,共5页Journal of China Pharmaceutical University

基　　金：南京医科大学“科技创新基金”重大项目资助(No.2017NJMUCX004);江苏省自然科学基金资助项目(No.BK20161033)。

摘　　要：考察利多卡因对脂多糖(lipopolysaccharide,LPS)诱导急性肺损伤(ALI)小鼠模型血浆中基质金属蛋白酶MMP-9和MMP-2活性的影响,并探讨其改善LPS诱导的急性肺损伤的作用机制。小鼠尾静脉注射不同浓度的利多卡因(2,4,8 mg/kg,iv)预处理30 min,再腹腔注射LPS 10 mg/kg刺激12 h建立小鼠ALI模型,测定小鼠7 d存活率及肺组织湿/干重比;Western blot法检测肺组织中p38 MAPK的磷酸化水平;明胶酶谱法测定血浆中MMP-9和MMP-2活性。实验结果发现,利多卡因预处理可剂量依赖性提高ALI小鼠存活率,降低肺组织湿/干重比,抑制血浆中MMP-9和MMP-2活性,并下调肺组织中p38的磷酸化水平。研究结果表明,利多卡因改善LPS诱导的小鼠急性肺损伤,其机制可能与抑制基质金属蛋白酶的活化有关。The aim of the present study was to investigate the effects and mechanisms of lidocaine on lipopolysaccharide(LPS)-induced matrix metalloproteinase(MMP)-9 and MMP-2 activity in plasma,and the effects of lidocaine on LPS-induced acute lung injury(ALI).Mice were pretreated with lidocaine(2,4,8 mg/kg)for 30 minutes,and then treated with 10 mg/kg LPS(ip)for 12 h to induce ALI.The 7-day survival rate and lung wet/dry weight ratio of mice were monitored.Phosphorylation level of p38 was measured by western blot.The activity of MMP-9 and MMP-2 in plasma was evaluated by gelatin zymography.The results showed that pretreatment with lidocaine could significantly reduce the death rate of ALI mice as well as the lung wet/dry weight ratio in a dose-dependent manner and suppress the activity of MMP-9 and MMP-2 in plasma.Moreover,lidocaine also markedly inhibited LPS-induced upregulation of p-p38 in a dose-dependent manner.In conclusion,lidocaine alleviated LPS-induced acute lung injury by suppressing MMP-9 and MMP-2 activity.

关 键 词：利多卡因 脂多糖 急性肺损伤 基质金属蛋白酶 

分 类 号：R965[医药卫生—药理学]