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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
                                                                                                Δ

                 1*
                           2
          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
                     1
                                   2
          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 ·
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