Inflammatory and transcriptional roles of poly (ADP-ribose) polymerase in ventilator-induced lung injury
- Authors
- Kim, Je Hyeong; Suk, Min Hyun; Yoon, Dae Wui; Kim, Hye Young; Jung, Ki Hwan; Kang, Eun Hae; Lee, Sung Yong; Lee, Sang Yeub; Suh, In Bum; Shin, Chol; Shim, Jae Jeong; In, Kwang Ho; Yoo, Se Hwa; Kang, Kyung Ho
- Issue Date
- 2008
- Publisher
- BMC
- Citation
- CRITICAL CARE, v.12, no.4
- Indexed
- SCIE
SCOPUS
- Journal Title
- CRITICAL CARE
- Volume
- 12
- Number
- 4
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/125554
- DOI
- 10.1186/cc6995
- ISSN
- 1466-609X
- Abstract
- Introduction Poly (ADP-ribose) polymerase ( PARP) participates in inflammation by cellular necrosis and the nuclear factor-kappa-B (NF-kappa B)-dependent transcription. The purpose of this study was to examine the roles of PARP in ventilator-induced lung injury (VILI) in normal mice lung. Methods Male C57BL/6 mice were divided into four groups: sham tracheostomized (sham), lung-protective ventilation (LPV), VILI, and VILI with PARP inhibitor PJ34 pretreatment (PJ34+VILI) groups. Mechanical ventilation (MV) settings were peak inspiratory pressure (PIP) 15 cm H2O + positive end-expiratory pressure (PEEP) 3 cm H2O + 90 breaths per minute for the LPV group and PIP 40 cm H2O + PEEP 0 cm H2O + 90 breaths per minute for the VILI and PJ34+ VILI groups. After 2 hours of MV, acute lung injury (ALI) score, wet-to-dry (W/D) weight ratio, PARP activity, and dynamic compliance (CD) were recorded. Tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), myeloperoxidase (MPO) activity, and nitrite/nitrate (NOX) in the bronchoalveolar lavage fluid and NF-.B DNA-binding activity in tissue homogenates were measured. Results The VILI group showed higher ALI score, W/D weight ratio, MPO activity, NOX, and concentrations of TNF-alpha and IL-6 along with lower CD than the sham and LPV groups (P < 0.05). In the PJ34+ VILI group, PJ34 pretreatment improved all histopathologic ALI, inflammatory profiles, and pulmonary dynamics (P < 0.05). NF-kappa B activity was increased in the VILI group as compared with the sham and LPV groups (P < 0.05) and was decreased in the PJ34+ VILI group as compared with the VILI group (P = 0.009). Changes in all parameters were closely correlated with the PARP activity (P < 0.05). Conclusion Overactivation of PARP plays an important role in the inflammatory and transcriptional pathogenesis of VILI, and PARP inhibition has potentially beneficial effects on the prevention and treatment of VILI.
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