摘要
目的:探讨金振口服液(JZKFY)对脂多糖(LPS)致急性肺损伤(ALI)模型小鼠的影响及其分子水平作用机制。方法:小鼠随机分为正常组、模型组、醋酸地塞米松组、金振口服液高、中、低(4.4,2.2,1.1 g·kg(-1))剂量组,各给药组给予相应剂量药物,正常组和模型组灌胃同等剂量的生理盐水,1次/d,连续7 d后,模型组及药物组小鼠腹腔注射LPS(10 mg·kg(-1))复制急性肺损伤小鼠模型,正常组腹腔注射同等剂量的生理盐水。6 h后采集小鼠肺组织,测定左肺湿/干质量比(W/D);酶联免疫吸附法(ELISA)检测肺组织中肿瘤坏死因子-α(TNF-α),白细胞介素(IL)-1β;蛋白免疫印迹法(Western blot)测定肺组织中p65,IκBα,ERK1/2,p38蛋白及其磷酸化蛋白表达水平。结果:与正常组比较,模型组小鼠W/D显著升高(P〈0.01),肺组织中TNF-α,IL-1β水平显著升高(P〈0.01),p65,IκBα,ERK1/2,p38蛋白磷酸化水平显著上调(P〈0.01)。与模型组比较,金振口服液低、高剂量及地塞米松组W/D显著降低(P〈0.05,P〈0.01);金振口服液各剂量组及地塞米松组肺组织中TNF-α,IL-1β水平显著降低;金振口服液各剂量组及地塞米松组p65,IκBα,p38蛋白磷酸化水平显著下调(P〈0.05,P〈0.01),金振口服液高剂量、地塞米松组ERK1/2蛋白磷酸化水平显著下调(P〈0.05,P〈0.01)。结论:金振口服液能够有效改善LPS诱导的ALI肺组织间质性水肿及降低致炎细胞因子的含量,其作用机制与抑制p65,IκBα,ERK1/2,p38多个靶蛋白磷酸化,从而阻断核转录因子-κB(NF-κB),丝裂原活化蛋白激酶(MAPK)炎症通路的信号传导密切相关。
Objective:To explore the effect and mechanism of Jinzhen oral liquid(JZOL) on lipopolysaccharide(LPS)-induced acute lung injury(ALI) model in mice.Method:Mice were randomly divided into normal control group,model group,dexamethasone group(DEX),JZOL high(JZOLG),medium(JZOLZ)and low(JZOLD) dose(4.4,2.2,1.1 g·kg^(-1)) groups.Corresponding dose of medicine was given in the treatment groups,and the mice in normal group and model group received the same dose of normal saline,once a day for 7 days.Then the ALI models were induced by intraperitoneal injection of LPS(10 mg·kg^(-1)),while the mice in normal group received intraperitoneal injection of the same dose of normal saline.Six hour later,the lung tissues were taken; left lung wet-to-dry ratio(W/D) was measured; tumor necrosis factor(TNF)-α,and interleukin(IL)-1β in lung tissues were detected by enzyme-linked immunosorbent assay(ELISA); the protein expression levels of p65,IκBα,ERK1/2,p38 protein and their phosphorylation levels in lung tissues were detected by Western blot.Result:As compared with the normal group,the W/D,levels of TNF-α,IL-1β and the phosphorylation expression levels of p65,IκB,p38 protein were increased in the model group(P 〈 0.01).As compared with the model group,the W/D was significantly decreased in JZOLD,JZOLG and DEX groups; the levels of TNF-α and IL-1β were decreased significantly,and the phosphorylation expression levels of p65,IκB,p38 protein were significantly down-regulated in JZOLG,JZOLZ,JZOLD,and DEX groups(P 〈 0.05,P 0.01); and the phosphorylation expression level of ERK1/2 was significantly down-regulated in JZOLG and DEX groups(P 〈 0.05,P 〈 0.01).Conclusion:JZOLY can effectively improve the interstitial edema of the lung tissues and reduce inflammatory cytokines in mice with LPS-induced ALI.The mechanism is closely associated with inhibiting the phosphorylation levels of p65,IκBα,ERK1/2 and p38,blocking nuclear transcription factor-kappa B(NF-κB) and mitogen activated protein kinase(MAPK) inflammatory pathway.
作者
宗绍波
孙兰
吕耀中
周军
王振中
萧伟
ZONG Shao-bo;SUN Lan;LYU Yao-zhong;ZHOU Jun;WANG Zhen-zhong;XIAO Wei(Jiangsu Kanion Parmaceutical Co. Ltd. , State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Lianyungang 222001, China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2018年第9期155-159,共5页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家“重大新药创制”科技重大专项(2013ZX09402203)
关键词
金振口服液
急性肺损伤
脂多糖
丝裂原活化蛋白激酶
核转录因子-ΚB
Jinzhen oral liquid
acute lung injury
lipopolysaccharide (LPS)
mitogen activated protein kinase (MAPK)
nuclear transcription factor-kappa B (NF-κB)