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·药学研究·
补阳还五汤对特发性肺纤维化模型大鼠的改善作用机制
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刘必旺 ,赵 换(1.山西中医药大学傅山学院,山西 晋中 030619;2.山西中医药大学附属医院药剂科,
太原 030024)
中图分类号 R965 文献标志码 A 文章编号 1001-0408(2023)14-1671-05
DOI 10.6039/j.issn.1001-0408.2023.14.02
摘 要 目的 研究补阳还五汤(BYHW)对特发性肺纤维化模型大鼠的改善作用机制。方法 将96只Wistar大鼠随机分成空白
组、模型组、阳性对照组和BYHW低、中、高剂量组,每组16只。除空白组外,其余各组大鼠采用气管滴注博来霉素(5 mg/kg)方法
造模。造模当天开始给药,空白组和模型组大鼠按 10 mL/kg 灌胃生理盐水,阳性对照组大鼠按 5 mg/kg 灌胃地塞米松溶液,
BYHW低、中、高剂量组大鼠按2.5、5、10 g/kg(以生药量计)灌胃药液,每天1次,连续给药28 d。测量各组大鼠造模第0、7、14、21、
28天的体重;动态可视化观察肺细静脉内黏附白细胞数量;检测血清中肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)含量,肺组织
中TNF-α、IL-6、羟脯胺酸(HYP)、转化生长因子β1 (TGF-β1 )含量,肺组织中紧密连接蛋白1(ZO-1)蛋白表达;观察肺组织的病理形
态学变化。结果 与模型组比较,补阳还五汤高、中剂量组和阳性对照组大鼠造模第14、21、28天时体重均显著升高,肺细静脉内
黏附白细胞数量均显著减少,血清和肺组织中TNF-α(BYHW中剂量组血清除外)、IL-6含量以及肺组织中HYP、TGF-β1含量均显
著降低,肺组织中ZO-1蛋白表达均显著升高(P<0.05或P<0.01);肺组织病理变化均不同程度改善。结论 BYHW可能从改善肺
微循环的白细胞黏附、抗炎、抗纤维化等方面发挥抗肺纤维化的作用。
关键词 补阳还五汤;肺纤维化;微循环;紧密连接蛋白1
Improving mechanism of Buyang huanwu decoction on idiopathic pulmonary fibrosis model rats
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LIU Biwang ,ZHAO Huan (1. Fushan College, Shanxi University of Chinese Medicine, Shanxi Jinzhong
030619, China;2. Dept. of Pharmacy, the Affiliated Hospital of Shanxi University of Chinese Medicine,
Taiyuan 030024, China)
ABSTRACT OBJECTIVE To study the improving mechanism of Buyang huanwu decoction (BYHW) on idiopathic pulmonary
fibrosis (IPF) model rats. METHODS Ninety-six Wistar rats were randomly divided into blank group, model group, positive
control group, and BYHW low-dose, middle-dose and high-dose groups, with 16 rats in each group. Except for the blank group,
the IPF model was induced in other groups by intratracheal instillation of bleomycin (5 mg/kg). Starting from the day of modeling,
the blank group and model group were given normal saline (10 mL/kg) intragastrically, while the rats in the positive control group
were given dexamethasone solution (5 mg/kg) intragastrically, BYHW low-dose, middle-dose and high-dose groups were treated
with BYHW (2.5, 5, 10 g/kg, by crude drug) intragastrically, once a day, for 28 consecutive days. The body mass of rats in each
group was measured on days 0, 7, 14, 21 and 28 after modeling. The number of adherent white blood cells in pulmonary veins
was observed by a dynamic visualization system. The contents of TNF-α and IL-6 in serum and TNF-α, IL-6, HYP and TGF-β1 in
lung tissue were detected; the protein expression of ZO-1 was also detected. The pathomorphological changes in lung tissue were
observed. RESULTS Compared with the model group, the body weight of rats all increased significantly in BYHW high-dose and
middle-dose groups, positive control group, while the number of adherent white blood cells in pulmonary veins was decreased
significantly; the contents of TNF- α (except for serum in BYHW middle-dose group) and IL-6 in serum and lung tissue, the
contents of HYP and TGF-β1 in lung tissue were decreased significantly, while the protein expression of ZO-1 in the lung tissue
was increased significantly (P<0.05 or P<0.01). The pathological changes of lung tissue were improved to varying degrees.
CONCLUSIONS BYHW may play anti-pulmonary fibrosis
Δ 基金项目 国家自然科学基金重点支持项目(No.U21A20410); role by improving leukocyte adhesion, anti-inflammatory, anti-
山西省自然科学研究面上项目(No.202203021211217);山西中医药大
fibrosis, and other aspects of pulmonary microcirculation.
学2022年度科技创新团队项目(No.2022TD2005)
*第一作者 副教授,硕士生导师,博士。研究方向:方剂药理学。 KEYWORDS Buyang huanwu decoction; pulmonary
电话:0351-3179717。E-mail:LBW3084@sina.com fibrosis; microcirculation; zonula occludens-1
中国药房 2023年第34卷第14期 China Pharmacy 2023 Vol. 34 No. 14 · 1671 ·