Original Article

Surgery Today

, Volume 43, Issue 3, pp 293-299

Significant correlation between endothelial nitric oxide synthase (eNOS) expression and alveolar repair in elastase-induced rat pulmonary emphysema

  • Hiromichi ItoAffiliated withDepartment of Thoracic Surgery, Graduate School of Comprehensive Human Science, University of Tsukuba
  • , Shonosuke MatsushitaAffiliated withDepartment of Thoracic Surgery, Graduate School of Comprehensive Human Science, University of Tsukuba Email author 
  • , Shigemi IshikawaAffiliated withDepartment of Chest Surgery, International University of Health and Welfare Hospital
  • , Yukinobu GotoAffiliated withDepartment of Thoracic Surgery, Graduate School of Comprehensive Human Science, University of Tsukuba
  • , Mitsuaki SakaiAffiliated withDepartment of Thoracic Surgery, Graduate School of Comprehensive Human Science, University of Tsukuba
  • , Masataka OnizukaAffiliated withDepartment of Thoracic Surgery, Graduate School of Comprehensive Human Science, University of Tsukuba
  • , Yukio SatoAffiliated withDepartment of Thoracic Surgery, Graduate School of Comprehensive Human Science, University of Tsukuba
  • , Yuzuru SakakibaraAffiliated withDepartment of Thoracic Surgery, Graduate School of Comprehensive Human Science, University of Tsukuba

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Abstract

Background and purpose

Angiogenic factors, such as endothelial nitric oxide synthase (eNOS), are thought to play an important role in the repair of pulmonary emphysema (PE); yet, the correlation of the factors involved has not been investigated. We conducted this study to clarify the positive correlation between eNOS expression and alveolar repair in PE recovery.

Methods

We used elastase to induce PE in rats, which were divided into Groups A (Control), B (G-CSF), C (PE) and D (PE + G-CSF). G-CSF was injected for 12 days, 4 weeks after which the alveolar walls, arterioles, and angiogenic factors including eNOS were examined histopathologically and by western blotting.

Results

In comparing Groups A, B, C, and D, the alveolar density was 2.4 ± 0.2, 2.4 ± 0.1, 1.8 ± 0.1, 2.5 ± 0.1 per 100 μm2, respectively (C vs. others; p < 0.00001) and the number of arterioles was 4.5 ± 1.0, 5.6 ± 0.6, 3.2 ± 0.5, 5.5 ± 0.7/mm2, respectively (C vs. others; p < 0.05). Immunohistochemical staining (IHC) revealed different eNOS expression in Group D versus Group C (p < 0.0001) and western blotting revealed different eNOS, VEGF, and FLT-1 expression in Group D versus Group C (p < 0.01, p < 0.05, p < 0.001), reflecting the contribution of angiogenesis to PE repair. eNOS showed a significantly positive correlation to alveolar density and arteriole repair.

Conclusion

Alveolar repair was correlated positively with eNOS expression by vascular regeneration in elastase-induced rat PE.

Keywords

Neovascularization Emphysema eNOS Angiogenic factor G-CSF