摘要
目的研究老鹳草素(geraniin)对脂多糖(lipopolysaccharide,LPS)诱导的小鼠急性肺损伤(acute lung injury,ALI)的保护作用机制。方法48只BALB/c小鼠(雌性,4周龄,18~22g)随机分为空白组(control组)、LPS组、地塞米松组(Dex组,2 mg/kg)、老鹳草素低剂量组(LD组,10 mg/kg)、老鹳草素中剂量组(MD组,20 mg/kg)、老鹳草素高剂量组(HD组,40 mg/kg),每组8只。空白组和LPS组灌胃生理盐水,地塞米松组灌胃地塞米松,老鹳草素各剂量组灌胃相应剂量的药物,生理盐水与各个受试药物均每日1次,连续3 d。末次给药1 h后,除空白组外的其余各组均鼻内滴注LPS(4 mg/kg)构建急性肺损伤模型。造模6 h后,检测各组小鼠肺湿干(wet-to-dry,W/D)质量比。采用HE染色法观察肺组织的病理学改变,测定血液及肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中炎性细胞数;采用酶联免疫吸附法(ELISA)检测血清及BALF中白细胞介素6(IL-6)、白细胞介素-1β(IL-1β)、肿瘤坏死因子α(TNF-α)含量;采用免疫组织化学法检测磷酸化核因子-κBp65(p-NF-κBp65)的表达。结果与空白组相比,LPS组小鼠肺泡结构破坏、炎性细胞浸润,血清及BALF中IL-6、IL-1β、TNF-α含量、肺W/D比值、BALF中巨噬细胞数目及中性粒细胞数目、肺组织中p-NF-κBp65的相对表达量均显著升高(P<0.01)。与LPS组比较,各给药组中的肺组织病理状态明显得到改善;血清及BALF中IL-6、IL-1β、TNF-α含量、肺W/D比值、BALF中巨噬细胞数目及中性粒细胞数目、肺组织中p-NF-κBp65的相对表达量均显著降低(P<0.05)。结论老鹳草素对小鼠急性肺损伤具有保护作用,其作用机制可能与其抑制p-NF-κBp65表达、从而减少炎症因子IL-6、IL-1β、TNF-α分泌有关。
Objective To explore the protective mechanism of geraninn on acute lung injury(ALI)induced by lipopolysaccharide(LPS)in mice.Methods Forty-eight BALB/c mice(female,4 weeks old,18~22 g)were randomly divided into 6 groups(n=8):the blank group(control group),the LPS group,the dexamethasone group(Dex group,2 mg/kg),the geraninn low dose group(LD group,10 mg/kg),the geraninn medium dose group(MD gruop,20 mg/kg)and the geraninn high dose group(HD group,40 mg/kg).The mice in blank group and LPS group were fed with normal saline,the mice in the Dex group were fed with dexamethasone and the mice in geraniin groups were given corresponding dose of drugs.Normal saline and all tested drugs were given once a day for 3 d.In 1 h later after the last administration,the acute lung injury model was established by using intranasal drip of LPS(4 mg/kg)in all groups except the blank group.In 6 h after modeling,the wet-to-dry(W/D)weight ratio of the lung tissues of mice in each group was collected.The pathological changes of lung tissue were observed by HE staining,and the number of inflammatory cells in broncho alveolar lavage fluid(BALF)and blood was measured;The levels of interleukin-6(IL-6),interleukin-1βand tumor necrosis factorα(TNF-α)in plasma and BALF were detected by ELISA.The amount of p-NF-κBp65 was detected by immunohistochemical method.Results Compared with the blank group,the alveolar structure in LPS group was destroyed,inflammatory cell infiltrated,and the contents of IL-6,IL-1βand TNF-αin serum and BALF in the LPS group increased;The W/D weight ratio of the lung tissues,the number of macrophages and neutrophils in BALF and serum,the relative expression of p-NF-κBp65 in lung tissue also increased(P<0.01).Compared with the LPS group,pathological state of the lung tissues improved obviously among the groups(except the blank group);The contents of IL-6,IL-1β,TNF-αin the serum and BALF,the W/D ratio of the lung tissues,the numbers of macrophages and neutrophils in BALF and the relative expression of p-NF-κBp65 of
作者
王静
李雪
朱庆林
王文婷
李宛蓉
江仁义
黄蒙蒙
郜静欣
尹陈晨
WANG Jing;LI Xue;ZHU Qinglin;WANG Wenting;LI Wanrong;JIANG Renyi;HUANG Mengmeng;GAO Jingxin;YIN Chenchen(School of Biological and Food Engineering,Suzhou University,Suzhou,Anhui Province,234000,China)
出处
《陆军军医大学学报》
CAS
CSCD
北大核心
2022年第22期2300-2306,共7页
Journal of Army Medical University
基金
安徽省创新训练项目(S202010379065)
安徽省自然科学基金青年项目(2208085QH261)
宿州学院科研平台开放课题(2020ykf19)
