和厚朴酚对脂多糖诱导的急性肺损伤小鼠的保护作用  

Protective Effect of Honokiol on Lipopolysaccharide-induced Acute Lung Injury Mice

作　　者：王林[1] 李红波[2] 刘南[1] 赵静[1] 段鹏凯[2] 刘亚楠[3] 

机构地区：[1]广州中医药大学第一附属医院急诊科,广东广州510405 [2]广州军区广州总医院重症医学科,广东广州510010 [3]南方医科大学,广东广州510515

出　　处：《中药新药与临床药理》2016年第6期810-815,共6页Traditional Chinese Drug Research and Clinical Pharmacology

摘　　要：目的探讨和厚朴酚(HNK)对脂多糖(LPS)诱导的急性肺损伤小鼠的保护作用。方法选取SPF级BALB/c小鼠40只,随机分为5组,每组8只,即正常组,模型组,HNK高、低剂量组,地塞米松(DEX)组,利用LPS诱导小鼠急性肺损伤(ALI)模型,和厚朴酚腹腔注射后检测肺干湿比值(W/D)、进行支气管肺泡灌洗液(BALF)中性粒细胞计数、检测血气分析、计算肺泡液体清除率(AFC)等。ELISA法检测各组小鼠血清中TNF-α和细胞因子IL-1β表达的变化,Western blot法和Real time PCR检测各组小鼠肺组织MMP-9和NF-κB表达。结果模型组中,小鼠BALF中中性粒细胞计数、肺W/D比值、TNF-α、IL-1β、MMP-9以及NF-κB水平明显增高,与正常组比较,差异有统计学意义(P<0.05);小鼠PaO_2、酸碱度(pH)、AFC显著降低,与正常组比较,差异有统计学意义(P<0.05)。与模型组比较,HNK高、低剂量组,小鼠BALF中中性粒细胞计数、肺W/D比值、TNF-α、IL-1β、MMP-9以及NF-κB表达水平明显下降,PaO_2、p H、AFC显著上升,差异均有统计学意义(P<0.05)。结论和厚朴酚通过抑制NF-κB、MMP-9对LPS诱导的急性肺损伤发挥重要的保护作用。Objective To investigate the protective effect of honokiol（HNK）on mice with acute lung injury induced by lipopolysaccharide（LPS）.Methods Forty SPF BALB/c mice were randomly dived into 5 groups,namely placebo control group,LPS group,low-dose HNK group,high-dose HNK group,and dexamethasone（Dex）group,8 mice in each group.Acute lung injury mice model was induced by LPS.After intraperitoneal injection of HNK,the ratio of mice lung wet mass to dry mass（W/D）was measured,neutrophilic granulocytic count in bronchoalveolar lavage fluid（BALF）was determined,arterial blood gas analysis was performed,and alveolar fluid clearance（AFC） was calculated.The expression levels of tumor necrosis factor alpha（TNF-α） and interleukin-1β（IL-1β） were detected by ELISA.The expression levels of matrix metalloproteinase-9（MMP-9）and nuclear factor kappa B（NF-κB）were examined by Western blot and real-time PCR.Results The neutrophilic granulocytic count in BALF,lung W/D ratio,and the expression levels of TNF-α,IL-1β,MMP-9 and NF-κB of mice were significantly increased in LPS group（P〈0.05）,and arterial partial pressure of oxygen（Pa O2）,p H,and AFC were dramatically decreased（P〈0.05）as compared with the placebo control group.In low-and high-dose HNK groups,the neutrophilic granulocytic count in BALF,lung W/D ratio,and the expression levels of TNF-α,IL-1β,MMP-9 and NF-κB of mice were significantly reduced（P〈0.05）,and the arterial partial pressure of oxygen（Pa O2）,p H,and AFC were markedly increased（P〈0.05）as compared with the model group.Conclusion HNK exerts certain protective effect on LPS-induced acute lung injury in mice,The mechanism may be related to the inhibition of MMP-9 and NF-κB expression.

关 键 词：和厚朴酚 脂多糖 急性肺损伤 NF-κB MMP-9 小鼠 

分 类 号：R285.5[医药卫生—中药学]