紫草素对肺炎链球菌引起的肺炎小鼠细胞外信号调节激酶/p38丝裂素活化蛋白激酶/核苷酸结合寡聚化结构域样蛋白3信号通路及肺血管通透性的影响  

Effects of shikonin on ERK/p38/NLRP3 signaling pathway and pulmonary vascular permeability in streptococcus pneumoniae induced pneumonia mice

作　　者：卫丽[1] 刘虹[1] 闫鲜鹏[1] WEI Li;LIU Hong;YAN Xianpeng(Author Affiliation:Department of Pediatrics,Shaanxi Provincial People's Hospital,Xi'an,Shaanxi 710068,China)

机构地区：[1]陕西省人民医院儿科,陕西西安710068

出　　处：《安徽医药》2021年第11期2159-2164,I0002,共7页Anhui Medical and Pharmaceutical Journal

摘　　要：目的探究紫草素对肺炎链球菌引起的肺炎小鼠细胞外信号调节激酶/p38丝裂素活化蛋白激酶/核苷酸结合寡聚化结构域样蛋白3(ERK/p38/NLRP3)信号通路及肺血管通透性的影响。方法采用肺炎链球菌悬液50 L滴加BALB/c小鼠破损鼻黏膜建立肺炎链球菌性肺炎模型,成模小鼠采用随机数字表法分为模型组、紫草素低、中、高浓度组及头孢呋辛酯组,另取鼻腔滴加50 L生理盐水BALB/c小鼠为对照组,每组10只,紫草素低、中、高浓度组分别给予紫草素12.5 mg/kg、25.0 mg/kg、50.0 mg/kg,头孢呋辛酯组给予头孢呋辛酯50.0 mg/kg,对照组、模型组给予等量生理盐水,每天1次,连续灌胃7 d。末次给药12 h后处死小鼠,检测各组小鼠左肺湿/干重比值(W/D),每组采用随机数字表法选取4只小鼠进行1%伊文氏蓝5 mL/kg尾静脉注射检测肺血管通透性,酶联免疫吸附试验(ELISA)检测肺组织白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)表达量,实时荧光定量聚合酶链式反应(RT-qPCR)及蛋白质印迹法(WB)分别检测肺组织ERK、p38、NLRP3 mRNA及蛋白表达。结果与对照组比较,模型组小鼠肺组织W/D比值[(4.49±0.27)%比(3.02±0.15)%]、肺血管通透性[(0.091±0.009)g/mg比(0.034±0.004)g/mg]、IL-1β[(567.29±14.65)pg/mL比(102.46±6.73)pg/mL]、TNF-α[(417.16±12.89)pg/mL比(83.59±6.28)pg/mL]、ERK、p38、NLRP3 mRNA及蛋白表达水平均显著增加(P<0.05);与模型组比较,紫草素低、中、高浓度组小鼠肺组织W/D比值、肺血管通透性、IL-1β、TNF-α表达量、ERK、p38、NLRP3 mRNA及蛋白表达水平均依次降低(P<0.05),紫草素高剂量组均低于头孢呋辛酯组(P<0.05)。结论紫草素可减轻肺炎链球菌性肺炎小鼠肺组织损伤、炎症反应及肺血管通透性,可能与抑制ERK/p38/NL‐RP3信号通路有关。Objective To investigate the effects of shikonin on extracellular signal-regulated kinase/p38 mitogen-activated protein kinase/nucleotide binding oligomerization domain like receptor protein 3(ERK/p38/NLRP3)signal pathway and pulmonary vascular permeability in Streptococcus pneumoniae induced pneumonia mice.Methods The pneumonia model of Streptococcus pneumoniae was established by dropping 50 L of Streptococcus pneumoniae suspension to the damaged nasal mucosa of BALB/c mice,the model mice were randomly divided into model group,low,medium and high concentrations of shikonin groups and cefuroxime axetil group,in addition,the BALB/c mice with 50 L normal saline added into the nasal cavity were taken as the control group,with 10 in each group.Shikonin of 12.5 mg/kg,25.0 mg/kg and 50.0 mg/kg were given to the low,medium and high concentration groups respectively,in cefu‐roxime axetil group,50.0 mg/kg cefuroxime axetil was given,the control group and the model group were given the same amount of nor‐mal saline,once a day gavage for 7 days.The mice were killed at 12 hours after the last administration,the ratio of left lung wet to dry weight(w/D)was measured,four mice in each group were randomly selected for 1%Evans Blue 5 mL/kg tail vein injection to detect pulmonary vascular permeability,the expressions of IL-1βand TNF-αin lung tissue were detected by enzyme-linked immunosorbent assay(ELISA),and the relative expressions of ERK,p38,NLRP3 mRNA and protein were detected by real-time fluorescent quantita‐tive PCR(RT-qPCR)and Western blot(WB)respectively.Results Compared with those in the control group,the W/D ratio of lung tis‐sue,pulmonary vascular permeability,expressions of IL-1βand TNF-α,and the expression levels of ERK,p38,NLRP3 mRNA and pro‐tein of mice in the model group were significantly higher(P<0.05);compared with those in the model group,the W/D ratio of lung tis‐sue[(4.49±0.27)%vs.(3.02±0.15)%],pulmonary vascular permeability[(0.091±0.009)g/mg vs.(0.034±0.004)g/mg],expressions of IL-1β[(

关 键 词：紫草素 肺炎链球菌 肺炎 小鼠 肺血管通透性 细胞外信号调节激酶/p38丝裂素活化蛋白激酶/核苷酸结合寡聚化结构域样蛋白3信号通路 

分 类 号：R285.5[医药卫生—中药学]