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清肺保元胶囊对COPD模型大鼠气道炎症的抑制作用及对NLRP3
信号通路的影响 Δ
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胡万福 ,刘 明 ,杨 燕 ,李 玲 ,李广松(1.贵州中医药大学第一附属医院药剂科,贵阳 550002;2.贵州
中医药大学基础医学院药理学教研室,贵阳 550025;3.贵州医科大学组织工程与干细胞实验中心,贵阳
550025)
中图分类号 R285.5 文献标志码 A 文章编号 1001-0408(2021)03-0309-05
DOI 10.6039/j.issn.1001-0408.2021.03.10
摘 要 目的:探讨清肺保元胶囊对慢性阻塞性肺疾病(COPD)模型大鼠气道炎症的抑制作用,以及对 NOD 样受体蛋白 3
(NLRP3)信号通路的影响。方法:将60只SD雄性大鼠随机分为空白对照组、模型组、地塞米松组(阳性对照,0.2 mg/kg)和清肺保
元胶囊高、中、低剂量组(1 232.0、616.0、308.0 mg/kg),每组10只。除空白对照组外,其余各组大鼠经烟熏28 d和气管内滴注脂多
糖2次以复制COPD模型。自实验第29天起,空白对照组和模型组大鼠灌胃等体积生理盐水,各给药组大鼠灌胃相应药物;给药
体积均为10 mL/kg,每日1次,连续28 d。末次给药后,检测各组大鼠肺功能;采用苏木精-伊红染色法观察其肺组织病理学变化,
采用酶联免疫吸附测定法检测其支气管肺泡灌洗液中白细胞介素1β(IL-1β)的含量并进行白细胞计数;采用Western blotting法检
测其肺组织中NLRP3、剪切的胱天蛋白酶1(Cleaved caspase-1)蛋白的相对表达量。结果:模型组、地塞米松组和清肺保元胶囊高、
中、低剂量组分别有3、2、1、1、2只大鼠死亡。与空白对照组比较,模型组大鼠第0.3秒用力呼气容积/用力肺活量比值(FEV0.3/FVC)
显著降低(P<0.01);其肺组织可见大量炎性细胞浸润,病变明显;其支气管肺泡灌洗液中IL-1β含量和白细胞计数以及肺组织中
NLRP3、Cleaved caspase-1蛋白的相对表达量均显著升高(P<0.05或P<0.01)。与模型组比较,各给药组大鼠FEV0.3/FVC均显著
升高(P<0.05或P<0.01);其肺组织病变不同程度地改善;其肺泡灌洗液中IL-1β含量和白细胞计数,肺组织中NLRP3蛋白(清肺
保元胶囊低剂量组除外)和 Cleaved caspase-1 蛋白(清肺保元胶囊中、低剂量组除外)的相对表达量均显著降低(P<0.05 或 P<
0.01)。结论:清肺保元胶囊可减轻COPD模型大鼠的肺组织病理损伤、改善其肺功能,这种作用可能与抑制NLRP3信号通路进而
抑制炎症反应有关。
关键词 清肺保元胶囊;慢性阻塞性肺疾病;气道炎症;NOD样受体蛋白3信号通路;大鼠
Inhibitory Effects of Qingfei Baoyuan Capsule on Airway Inflammation in Rats with Chronic Obstructive
Pulmonary Disease and Its Effect on NLRP3 Signaling Pathway
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HU Wanfu ,LIU Ming ,YANG Yan ,LI Ling ,LI Guangsong(1. Dept. of Pharmacy,the First Affiliated Hospital
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of Guizhou University of TCM,Guiyang 550002,China;2. Dept. of Pharmacology,School of Basic Medicine,
Guizhou University of TCM, Guiyang 550025,China;3. Center for Tissue Engineering and Stem Cell
Experiment,Guizhou Medical University,Guiyang 550025,China)
ABSTRACT OBJECTIVE:To investigate inhibitory effects of Qingfei baoyuan capsule on airway inflammation in rats with
chronic obstructive pulmonary disease(COPD),and its effects on NLRP3 signaling pathway. METHODS:Totally 60 SD male rats
were randomly divided into blank control group,model group,dexamethasone group (positive control,0.2 mg/kg),Qingfei
baoyuan capsule high-dose,medium-dose and low-dose groups(1 232.0,616.0,308.0 mg/kg),with 10 rats in each group. Except
for blank control group,other groups were fumigated for 28 days and given intratracheal dripping of lipopolysaccharide twice to
induce COPD model. Since the 29th day after modeling,blank control group and model group were given constant volume of
normal saline intragastrically,and administration groups were given related medicine intragastrically. The administration volume
was 10 mL/kg,once a day,for consecutive 28 days. After last administration,the lung function was detected. The pathological
changes of lung tissue were observed by HE staining. The content of interleukin-1 β (IL-1 β) in bronchoalveolar lavage fluid
(BALF)were detected by ELISA,and the number of leukocytes was counted;the expression of NLRP3 and Cleaved caspase-1 in
lung tissue of rats were detected by Western blotting assay.
Δ 基金项目:全国中药特色技术传承人才培训项目(No.国中医药
RESULTS:Three,two,one,one and two rats died in model
人教函〔2018〕204 号);贵州省科技计划项目(No.黔科合 LH 字〔2017〕
group, dexamethasone group, Qingfei baoyuan capsule
7150号)
*副主任药师,硕士。研究方向:中药复方制剂。电话:0851- high-dose,medium-dose and low-dose groups,respectively.
85638525。E-mail:357480063@qq.com Compared with blank control group,FEV0.3/FVC of rats in
# 通信作者:主任药师。研究方向:医院制剂质量控制。电话: model group was significantly decreased (P<0.01). A large
0851-85639479。E-mail:1654226588@qq.com number of inflammatory cells infiltration were found in the
中国药房 2021年第32卷第3期 China Pharmacy 2021 Vol. 32 No. 3 ·309 ·