天津医药 ›› 2021, Vol. 49 ›› Issue (6): 598-602.doi: 10.11958/202013011

• 实验研究 • 上一篇    下一篇

阿托伐他汀钙对COPD模型大鼠肺血管重塑的影响及机制探讨

何永鸿,强丽,王宋平   

  1. 1西南医科大学附属医院呼吸与危重医学科(邮编646000),2感染科
  • 收稿日期:2020-11-02 修回日期:2021-02-24 出版日期:2021-06-15 发布日期:2021-06-15
  • 通讯作者: 何永鸿 E-mail:1007175340@qq.com

The effect of atorvastatin calcium on pulmonary vascular remodeling in chronic obstructive pulmonary disease rats #br#

HE Yong-hong, QIANG Li, WANG Song-ping   

  1. 1 Department of Respiratory and Critical Care Medicine, 2 Department of Infectious Disease, the Affiliated Hospital of
    Southwest Medical University, Luzhou 646000, China

  • Received:2020-11-02 Revised:2021-02-24 Published:2021-06-15 Online:2021-06-15
  • Contact: yonghong he E-mail:1007175340@qq.com

摘要: 目的 探讨阿托伐他汀钙对慢性阻塞性肺疾病(COPD)大鼠肺血管重塑的调节机制及对组蛋白脱乙酰 酶-2(HDAC2)的影响。方法 18只雌性SD大鼠按照随机数字表法分为空白对照组、COPD组、阿托伐他汀钙组,每 组6只。使用烟熏加气道滴入脂多糖法建立COPD模型,阿托伐他汀钙组于第2天开始,每天烟熏前30 min阿托伐他 汀钙片灌胃,剂量10 mg/ (kg·d),其余2组大鼠同时予以等量生理盐水灌胃,实验共6周。实验期间观察大鼠一般情 况变化,每2周称1次体质量。6周后HE染色和维多利亚蓝+苦味酸-酸性品红(VG)染色观察各组肺组织病理改变, 并对肺血管重塑程度进行评价。酶联免疫吸附测定(ELISA)法检测 HDAC2 含量,Western blot 法检测肺组织中 HDAC2 和血管内皮生长因子(VEGF)蛋白含量,实时荧光定量 PCR(qPCR)法检测肺组织 HDAC2 mRNA 表达。结果 实验第2、4、6周时,与空白对照组相比,COPD组大鼠体质量下降(P<0.05);与COPD组相比,阿托伐他汀钙组 大鼠体质量明显增加(P<0.05)。与空白对照组相比,COPD组的肺血管炎症、肺血管重构程度明显,血管壁面积/血 管总面积(WA%)、血管壁厚度/血管外径长度(WT%)明显增加,肺部炎症评分明显升高,血清和肺组织中HDAC2含 量明显降低,肺组织中VEGF水平升高(P<0.05)。与COPD组比较,阿托伐他汀钙组肺组织少量炎性细胞浸润,血管 病理改变较轻,WT%、WA%下降,肺部炎症评分降低,血清和肺组织HDAC2含量升高,VEGF表达减少(P<0.05)。 结论 阿托伐他汀钙可减轻COPD大鼠肺血管重塑的程度,其机制可能与增加HDAC2的表达有关。

关键词: 肺疾病, 慢性阻塞性, 阿托伐他汀钙, 大鼠, Sprague-Dawley, 组蛋白脱乙酰基酶2, 肺血管重塑

Abstract: Objective To investigate the regulatory mechanism of atorvastatin on pulmonary vascular remodeling and expression of histone deacetylation enzyme-2 (HDAC2) in chronic obstructive pulmonary disease (COPD) rats. Methods Eighteen female SD rats were randomly divided into control group, COPD group and atorvastatin calcium group, with 6 rats in each group. The COPD model was established by passive smoking and intratracheal injection of lipopolysaccharide. From the second day, atorvastatin group was intragastrically administered with atorvastatin 10 mg/(kg·d) half an hour prior to smoking, control group and COPD group were given equal amount of normal saline at the same time. The experiment lasted six weeks. The general condition of the rats was observed during the experiment, and the body weight was weighed every two weeks. After six weeks, Hematoxylin-eosinstaining and Victoria Blue + Van Gibson VG were used to observe lung tissue pathological changes, and the degree of pulmonary vascular remodeling was evaluated. HDAC2 was determined with ELISA. The protein expression of HDAC2 was measured by Western blot assay and HDAC2 mRNA was detected by qPCR. Results At the 2nd, 4th and 6th week, compared with the control group, the body weights were decreased in COPD group (P<0.05). Compared with COPD group, the weights of rats were increased in the atorvastain group (P<0.05). Compared with control group, the degree of pulmonary vascular inflammation and pulmonary vascular remodeling increased in COPD group, and the vascular wall area/total vascular area (WA% ), vascular wall thickness/vascular outer diameter length (WT% ), lung inflammation score increased significantly, with the serum and lung tissue expressions of HDAC2 decreased. The level of VEGF in the lung tissue increased (P<0.05). Compared with COPD group, the lung tissue showed less inflammatory cells in the atorvastatin group, and vascular pathological changes were significantly relieved. The WT% , WA% and lung inflammation score decreased significantly, with the expression of HDAC2 in the serum and lung tissue increased, and the level of VEGF in the lung tissue decreased (P<0.05). Conclusion Atorvastatin calcium can reduce the degree of pulmonary vascular remodeling in COPD rats by increasing the expression and level of HDAC2.

Key words: pulmonary disease, chronic obstructive, atorvastatin calcium, rats, Sprague-Dawley, histone deacetylase 2, pulmonary vascular remodeling