Abdominal sepsis is a common, life-threatening condition in the critically ill patients. The c-Jun N-terminal kinase (JNK) is known as a stress-activated protein kinase, in order to study the role of JNK on peritonitis-induced lung injury, the changes of plasma dihydrorhodamine 123 (DHR 123) oxidation level; the myeloperoxidase (MPO) and extravasations of Evans blue dye (EBD) of lung in wild-type (WT) mice with P. aeruginosa-induced peritonitis were determined first. Second, the specific JNK inhibitor, SP600125 or lefunomide, was given to WT mice immediately after P. aeruginosa injection and DHR oxidation, MPO activity, and EBD extravasations were examined. Third, JNK1-/- mice and JNK1+/- mice were subjected to peritonitis and assayed for DHR 123 oxidation, MPO activity, EBD extravasations, and reactive oxygen species (ROS). Fourth, chimeric mice (WT ¡÷ WT, JNK1-/- ¡÷ WT, WT¡÷JNK1-/-) were generated and used to determine the role of hematopoietic cells in peritonitis-induced lung damage. The results show that peritonitis induced DHR 123 oxidation; MPO activity and EBD extravasations in lungs and administration of specific JNK inhibitor decreased the peritonitis-induced DHR oxidation and lung damage. Also, both JNK1-/- and JNK1+/- mice showed a decreased DHR oxidation and lung damage after peritonitis. Finally, the decrease of DHR 123 oxidation, ROS, and lung damage in JNK1-/- ¡÷ WT chimeric mice suggests that that peritonitis-induced expression of iNOS and subsequent peroxynitrite production and lung damage depends on the JNK1 signaling of the hematopoietic cells.
| Identifer | oai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0804108-215703 |
| Date | 04 August 2008 |
| Creators | Tseng, Hsiu- Ting |
| Contributors | Chen, Lee-Wei, Tai, Ming-Hong, Hsu, Ching-Mei, Hsu, Li-Chung |
| Publisher | NSYSU |
| Source Sets | NSYSU Electronic Thesis and Dissertation Archive |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0804108-215703 |
| Rights | campus_withheld, Copyright information available at source archive |
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