阿托伐他汀对慢性阻塞性肺疾病大鼠肺血管重构的抑制作用。
Effects of atorvastatin in suppressing pulmonary vascular remodeling in rats with chronic obstructive pulmonary disease.
机构信息
Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou City, Sichuan Province, China.
Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou City, Sichuan Province, China.
出版信息
Clinics (Sao Paulo). 2023 Jul 15;78:100252. doi: 10.1016/j.clinsp.2023.100252. eCollection 2023.
OBJECTIVE
To investigate the effects of atorvastatin calcium on pulmonary vascular remodeling, the authors explored the regulatory mechanism of Histone Deacetylation Enzyme-2 (HDAC2) in rats with Chronic Obstructive Pulmonary Disease (COPD), and provided a new direction for drug treatment in the progression of vascular remodeling.
METHODS
Eighteen female SD rats were randomly divided into control (Group S1), COPD (Group S2), and atorvastatin calcium + COPD (Group S3) groups. A COPD rat model was established by passive smoking and intratracheal injection of Lipopolysaccharide (LPS). Haematoxylin and eosin staining and Victoria Blue + Van Gibson staining were used to observe pathological changes in the lung tissue. The pulmonary vascular inflammation score was calculated, and the degree of pulmonary vascular remodeling was evaluated. The ratio of Muscular Arteries in lung tissue (MA%), the ratio of the vessel Wall Area to the vessel total area (WA%), and the ratio of the vessel Wall Thickness to the vascular outer diameter (WT%) were measured using imaging software. The expression of HDAC2 was measured using western blotting, ELISA (Enzyme-Linked Immunosorbent Assay), and qPCR (Real-time PCR).
RESULTS
Compared with the control group, the degree of pulmonary vascular inflammation and pulmonary vascular remodeling increased in rats with COPD. The WT%, WA%, and lung inflammation scores increased significantly; the expression of HDAC2 and HDAC2mRNA in the serum and lung tissue decreased, and the level of Vascular Endothelial Growth Factor (VEGF) in the lung tissues increased (p < 0.05). Compared with the COPD group, the lung tissues from rats in the atorvastatin group had fewer inflammatory cells, and the vascular pathological changes were significantly relieved. The WT%, WA%, and lung inflammation scores decreased significantly; the expression of HDAC2 and HDAC2mRNA in the serum and lung tissues increased, and the level of VEGF in the lung tissues decreased (p < 0.05).
CONCLUSION
The present study revealed that atorvastatin calcium could regulate the contents and expression of HDAC2 in serum and lung tissues and inhibit the production of VEGF, thereby regulating pulmonary vascular remodeling in a rat model with COPD.
目的
探讨阿托伐他汀钙对慢性阻塞性肺疾病（COPD）大鼠肺血管重构的影响，研究组探索组蛋白去乙酰化酶-2（HDAC2）在 COPD 大鼠中的调节机制，为血管重构进展的药物治疗提供新方向。
方法
将 18 只雌性 SD 大鼠随机分为对照组（S1 组）、COPD 组（S2 组）和阿托伐他汀钙+COPD 组（S3 组）。通过被动吸烟和气管内注射脂多糖（LPS）建立 COPD 大鼠模型。苏木精和伊红染色及维多利亚蓝+范吉森染色观察肺组织病理变化，计算肺血管炎症评分，评估肺血管重构程度。采用图像软件测量肺组织中肌型动脉比例（MA%）、血管壁总面积与血管总面积比值（WA%）、血管壁厚度与血管外径比值（WT%）。采用 Western blot、ELISA（酶联免疫吸附试验）和 qPCR（实时 PCR）检测 HDAC2 的表达。
结果
与对照组相比，COPD 大鼠肺血管炎症和肺血管重构程度增加，WT%、WA%和肺炎症评分显著增加；血清和肺组织中 HDAC2 及 HDAC2mRNA 表达降低，肺组织血管内皮生长因子（VEGF）水平升高（p<0.05）。与 COPD 组相比，阿托伐他汀组大鼠肺组织炎症细胞减少，血管病理变化明显缓解，WT%、WA%和肺炎症评分显著降低；血清和肺组织中 HDAC2 及 HDAC2mRNA 表达升高，肺组织 VEGF 水平降低（p<0.05）。
结论
本研究表明，阿托伐他汀钙可调节 COPD 大鼠血清和肺组织中 HDAC2 的含量和表达，抑制 VEGF 的产生，从而调节 COPD 大鼠的肺血管重构。
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