Simvastatin mitigates functional and structural impairment of lung and right ventricle in a rat model of cigarette smoke-induced COPD

Int J Clin Exp Pathol. 2014 Dec 1;7(12):8553-62. eCollection 2014.

Abstract

Objectives: This study is conducted to investigate an effect of simvastatin on cigarette smoke-induced COPD.

Methods: Rats were exposed to air (control) and cigarette smoke (smoking) in presence and absence of simvastatin. Heart and lung tissues were harvested for histopathologic and morphometric analysis. Body weight of rat, mean liner intercept (MLI), mean alveolar number (MAN), lung function test, mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index (RVHI) and 5-HTT level in serum and BALF were examined in experimental rats, respectively.

Results: Application of simvastatin mitigated peribronchiolar inflammation and pulmonary bullae formed in the smoke-exposed lungs with weight gain as compared to the smoking rats (P < 0.05). Simvastatin-treated rats showed slight but significant decreases in MLI and MAN with a partial reversal of lung function decline (all P < 0.05). Treatment with simvastatin resulted in a significant decrease not only in mPAP and RVHI but also in a 5-HTT level in serum and BALF (P < 0.01 or 0.05) with a good correlation between the 5-HTT level and mPAP or RVHI (r = 0.693 and 0.479; 0.675 and 0.508).

Conclusion: Simvastatin partly reverses lung function decline and attenuates structural impairments of lung and right ventricle possibly through reducing 5-HTT content in the model of COPD.

Keywords: 5-hydroxytryptamine transporter; Simvastatin; cigarette smoke; peribronchiolar inflammation and pulmonary bullae.

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / chemistry
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Heart Ventricles / drug effects*
  • Heart Ventricles / pathology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Inflammation / etiology
  • Inflammation / pathology
  • Lung / drug effects*
  • Lung / pathology
  • Male
  • Pulmonary Disease, Chronic Obstructive / etiology
  • Pulmonary Disease, Chronic Obstructive / pathology*
  • RNA-Binding Proteins / analysis
  • RNA-Binding Proteins / biosynthesis*
  • Rats
  • Rats, Sprague-Dawley
  • Respiratory Function Tests
  • Simvastatin / pharmacology*
  • Smoking / adverse effects

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • RNA-Binding Proteins
  • Sert1 protein, rat
  • Simvastatin