冬凌草甲素对急性肺损伤小鼠肺组织炎症的抑制作用及相关机制研究  

Inhibitory Effect and Mechanism of Oridonin on Lung Inflammation in Mice with Acute Lung Injury

作　　者：郭民 高继萍 张瑞虎 景志杰 史泽雅 侯佳楠 霍怡彤 陈朝阳 GUO Min;GAO Jiping;ZHANG Ruihu;JING Zhijie;SHI Zeya;HOU Jianan;HUO Yitong;CHEN Zhaoyang(Laboratory of Animal Center,Shanxi Key Laboratory of Experimental Animal Science and Animal Model of Human Disease,Shanxi Mediral University,Iaiyuan 030001 Shanxi,China)

机构地区：[1]山西医科大学实验动物中心,实验动物与人类疾病动物模型,山西省重点实验室,山西太原030001

出　　处：《中药新药与临床药理》2022年第4期441-445,共5页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：山西省科技基础条件平台项目(201805D141008-3);山西省实验动物专项资金项目[2013(410)]。

摘　　要：目的研究冬凌草甲素(oridonin)对急性肺损伤(ALI)小鼠的抗炎作用及其机制。方法将24只Balb/c雄性小鼠随机分为4组:对照组、模型组、冬凌草甲素组和地塞米松(DEX)组,每组6只。小鼠腹腔注射冬凌草甲素(10 mg·kg^(-1))或地塞米松(5 mg·kg^(-1))1 h后,鼻内滴注脂多糖(0.5 mg·kg^(-1))作用12 h诱导急性肺损伤,设为冬凌草甲素组和地塞米松组;模型组小鼠仅鼻内滴注脂多糖作用12 h,建立急性肺损伤模型;对照组仅鼻内滴注等剂量生理盐水。采用HE染色检测肺组织病理损伤;酶联免疫吸附(ELISA)法检测支气管肺泡灌洗液(BALF)中肿瘤坏死因子α(TNF-α)、白细胞介素(IL)-1β、IL-6;Western Blot法检测肺组织核因子κB(NF-κB)p65、丝裂原活化蛋白激酶(MAPK)相关蛋白质(ERK、p38和JNK)磷酸化。结果与对照组比较,模型组肺组织出现明显病理损伤,中性粒细胞和巨噬细胞浸润增多(P<0.01);与模型组比较,冬凌草甲素组和地塞米松组小鼠肺组织中性粒细胞和巨噬细胞浸润减少(P<0.05)。与对照组比较,模型组支气管肺泡灌洗液中TNF-α、IL-1β和IL-6含量增加(P<0.01);与模型组比较,冬凌草甲素组和地塞米松组小鼠支气管肺泡灌洗液中TNF-α、IL-1β和IL-6含量减少(P<0.01)。与对照组比较,模型组肺组织磷酸化的p65、ERK、p38和JNK增多(P<0.01);与模型组比较,冬凌草甲素组和地塞米松组肺组织磷酸化的p65、ERK、p38和JNK减弱(P<0.05,P<0.01)。结论冬凌草甲素可减轻急性肺损伤小鼠肺组织炎症反应,其作用机制与抑制NF-κB和MAPK信号通路有关。Objective To study the anti-inflammatory effect of oridonin on acute lung injury(ALI)mice and its underlying mechanism. Methods Twenty-four Balb/c male mice were randomly divided into 4 groups: control group, model group(LPS), oridonin group and dexamethasone(DEX)group, six mice in each group. Oridonin group and DEX group were treated intraperitoneally with 10 mg·kg^(-1)of oridonin or 5 mg·kg^(-1)of DEX 1 h before lipopolysaccharide(0.5 mg·kg^(-1)) was given intranasally for 12 h. The ALI mice model was also established by intranasal administration of lipopolysaccharide for 12 h. The control group was instilled with the same dose of saline.H&E staining was used to detect the pathological damage of lung tissues,and ELISA method was used to assess tumor necrosis factor α(TNF-α),interleukin 1β(IL-1β),IL-6 in alveolar lavage fluid(BALF). Western blot was performed to evaluate the phosphorylation of nuclear factor κB(NF-κB) p65, mitogen-activated protein kinase(MAPK)related proteins(ERK,p38 and JNK). Results Compared with the control group,the lung injury of the model group was obvious, the infiltration of neutrophils and macrophages increased(P<0.01), whereas the infiltration of neutrophils and macrophages in oridonin and DEX groups declined compared with that in the model group(P<0.05). Compared with the control group,the TNF-α、IL-1β and IL-6 in BALF augmented(P<0.01).However,TNF-α、IL-1β and IL-6 in BALF in oridonin and DEX groups decreased compared with those in the model group(P<0.01). Compared with the control group, the levels of phosphorylation of p65, ERK, p38 and JNK were ascended(P<0.01). Nevertheless,the phosphorylation of p65,ERK,p38 and JNK was weakened in oridonin and DEX groups compared with those in the model group(P<0.05,P<0.01). Conclusion Oridonin could alleviate the inflammatory response in lung tissues of mice with acute lung injury via inhibiting NF-κB and MAPK signaling pathways.

关 键 词：冬凌草甲素 急性肺损伤 抑制 炎症因子 核因子κB(NF-κB) 丝裂原活化蛋白激酶(MAPK) 小鼠 

分 类 号：R285.5[医药卫生—中药学]