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Critical Care

Open Access

Possible involvement of rho kinase 1 (rock 1) in cecal ligation and puncture-induced sepsis

  • I Cinel1,
  • M Ark1,
  • H Kubat1,
  • T Karabacak1,
  • H Serinol1,
  • L Tamer1 and
  • U Oral1
Critical Care20059(Suppl 1):P84

https://doi.org/10.1186/cc3147

Published: 7 March 2005

We have previously demonstrated that following cecal ligation and puncture (CLP) there is an increase in lung epithelial apoptosis in a rat model [1]. On the other hand, it has been shown that the rho/rho kinase pathway is involved in mechanisms of several aspects such as endothelial cell dysfunction and apoptosis. However, the role of rho kinase in the concept of sepsis-induced apoptosis has yet to be elucidated. In this study, to investigate the possible contribution of rho/rho kinase signalling in CLP-induced lung injury, rho kinase expression and the possible protective effect of the administration of an inhibitor of rho kinase, (+)-(R)-trans-4-1-aminoethyl-N-4-pyridyl cyclohexanecarboxamide dihydrochloride monohydrate (Y-27632), has been investigated in rats in this model.

Thirty-two male Wistar rats were randomly divided into four groups: (1) sham, (2) CLP, (3) sham + Y27632, (4) CLP + Y27632. Y27632 was administered at 1.5 mg/kg, intaperitoneally, 20 min before performing operations. Twenty-four hours later, histopathology and apoptosis were assessed by H&E and immunohistochemically by caspase-3 to demonstrate septic lung injury. Additionally, expression of rock 1 and rock 2 proteins in lung tissue was analyzed by western blotting, and the contribution of oxidative damage was assessed by measuring the levels of thiobarbituric acid reactive substances (TBARS) and the 3-L-nitrotirozin (3-NT)/total tyrosine ratio.

The TBARS and 3-NT/total tirosine ratio levels in lung homogenates were found to be increased (11.05 ± 0.31 vs 29.855 ± 2.87) (0.1485 ± 0.10 vs 0.281 ± 0.05) in the CLP group compared with the sham group, and the administration of Y27632 prevented their increase (8.86 ± 1.87) (0.178 ± 0.02) significantly (P < 0.05). The number of apoptotic cells was significantly lower in the CLP + Y27632 group than CLP group and this finding was supported by caspase-3 expression in the lung. Lung histopathology was also protected by Y27632 in CLP-induced sepsis. Immunoblot experiments revealed the increased expression of active fragment of rock 1 in the CLP group. However, rock 2 expressions were similar in all groups.

In conclusion, since CLP induced active fragmentation of rock 1 and rho-kinase inhibitor prevented peroxynitrite-mediated apoptotic lung injury in this CLP-induced sepsis model, this suggests that rho-kinase plays an important role in apoptotic lung injury. Our data indicate that rock 1 or downstream components of this pathway may be potential targets for the development of novel therapies in sepsis.

Authors’ Affiliations

(1)
Mersin University School of Medicine, Mersin, Turkey

References

  1. Ozdülger A, Cinel I, Koksel O, et al.: The protective effect of N-acetylcysteine on apoptotic lung injury in cecal ligation and puncture-induced sepsis model. Shock 2003, 19: 366-372. 10.1097/00024382-200304000-00012PubMedView ArticleGoogle Scholar

Copyright

© BioMed Central Ltd 2005

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