柠檬苦素对脂多糖致小鼠急性肺损伤的作用  

Effects of limoninon on LPS-induced acute lung injury in mice

作　　者：王棣 张欢欢[2] 方杰[2] 钟宇森[2] 余陈欢[2] WANG Di;ZHANG Huanhuan;FANG Jie;ZHONG Yushen;YU Chenhuan(Jianggan People＇s Hospital of Hangzhou, Department of Internal Medicine, Hangzhou 310016, Zhejiang, Chi- na;Zhejiang Key Laboratory of Experimental Animal and Safety Evaluation, Zhefiang Academy of Medical Sciences, Hangzhou 310013, Zhejiang , China)

机构地区：[1]杭州市江干区人民医院内科,浙江杭州310016 [2]浙江省医学科学院,浙江省实验动物与安全性研究重点实验室,浙江杭州310013

出　　处：《中国临床药理学与治疗学》2018年第1期8-12,28,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金项目(81473339,81673583);浙江省科技厅院所专项(2014F10033)

摘　　要：目的:探讨柠檬苦素(LM)对脂多糖(LPS)致小鼠急性肺损伤的影响。方法:40只ICR雄性小鼠,按体质量随机分为4组:正常组、模型组、地塞米松(Dex)给药组和LM给药组,每组10只。Dex和LM均在滴注LPS前2 h分别小鼠腹腔注射10 mg/kg给药,之后除正常组小鼠只给予腹腔注射等体积的生理盐水外,其余小鼠气管滴注致死量的5 mg/kg LPS。LPS注射6 h后,处死小鼠,解剖小鼠取肺脏,计算小鼠肺指数、湿干比值。采用苏木素-伊红(HE)染色观察肺组织形态。采用ELISA法检测小鼠血清中TNF-α、IL-1β和IL-6含量;比色法检测血清髓过氧化物酶(MPO)含量。实时定量PCR检测TNF-α、IL-1β和IL-6mRNA表达情况。Western blot检测TLR4和NF-κB p65蛋白表达。结果:与正常组比较,模型组小鼠肺指数和湿干比值明显升高,肺组织间质炎性细胞浸润,伴明显的肺泡充血、水肿,血清MPO、TNF-α、IL-1β和IL-6含量及其肺组织mRNA表达量均明显升高(P<0.01);与模型组比较,LM给药组小鼠肺指数和湿干比值明显降低,肺组织病理状态明显改善,血清TNF-α、IL-1β和IL-6水平及肺组织TNF-αmRNA、IL-1βmRNA、IL-6 mRNA、TLR4和NF-κB p65蛋白表达量均明显降低(P<0.01)。结论:LM可通过调控TLR4/NF-κB通路抑制炎症因子的表达从而改善LPS诱导的小鼠肺组织损伤。AIM： To investigate the effects of limonin（ LM） on lipopolysaccharides（ LPS）-induced acute lung injury（ ALI） in mice.METHODS： Forty ICR male mice were divided randomly by weight into 4 groups： normal group,model group, dexamethasone（ Dex）-treated group and LM-treated group. Each group had ten mice. Dex and LM were intraperitoneally injected at the dose of10 mg/kg,respectively. Two hours after drug administration,except the mice in normal group treated with same vehicle,others were intracheally injected with LPS（ 5 mg/kg）. Six hours after LPS challenge,mice were sacrificed and lung tissues were obtained for calculating the pulmonary index and wet/dry mass（ W/D） ratio. The sections were stained with hematoxylin and eosin（ HE） for histological analysis. The levels of TNF-α,IL-1β,and IL-6 in serum were determined by ELISA. Myeloperoxidase（ MPO） in serum were determined by chromatometry. The mRNA expressions of TNF-α,IL-1β and IL-6 were determined by RT-PCR while TLR4 and NF-κB p65 protein by Western blot analysis. RESULTS： Compared with normal group,mice in model group had obvious increase of lung indexesand W/D ratios, which were accompanied by marked inflammatory cell infiltration,alveolar congestion and edema in lung; the levels of TNF-α,IL-1β,IL-6 and MPO in serum as well as their mRNA expressions in the lung of ALI mice were also increased（ P〈0. 01）. Compared with model group,lung indexes and W/D ratios were decreased in LMtreated group while histological changes were improved; the levels of TNF-α,IL-1β,and IL-6 in serum（ P〈0. 01） and their mRNA expressions,and the expressions of TLR4 and NF-κB p65 protein in lung tissues were also significantly decreased（ P〈0. 01）. CONCLUSION： LM protects against LPS-induced ALI via regulating TLR4/NF-κB pathway and inhibiting expression of inflammatory cytokines in mice.

关 键 词：柠檬苦素 抗炎作用 脂多糖 急性肺损伤 

分 类 号：R965.2[医药卫生—药理学]