[Protective effects and mechanism of SP600125 on lung ischemia/reperfusion injury in rats].

Abstract

OBJECTIVE:

To investigate the protective effects and mechanism of SP600125-specificity inhibitor of c-Jun N-terminal kinase (JNK)on lung ischemia /reperfusion injury in rats.

METHODS:

The unilateral lung ischemia/reperfusion model was replicated in vivo. Rats were randomly divided into three groups (n = 10): control group, ischemia/reperfusion group ( I/R group) and ischemia/reperfusion + SP600125 group (SP600125 group). The lung tissues sampled at the end of each experiment were assayed for wet/dry weight ratio (W/D),the injured alveoli rate (IAR), the expression of phosphorylation JNK (p-JNK) and JNK protein were detected by Western blot, the expression of Bcl-2, Bax, Caspase3 protein were detected by immunocytochemistry techniques, the pneumocyte apoptosis index (AI) was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end abeling(TUNEL), the ultrastructure changes were observed under electron microscope.

RESULTS:

Compared to I/R group, the expression of p-JNK, Bcl-2, Bax and caspase-3 protein were markedly decreased (all P < 0.01), the expression of Bcl-2 protein and the ratio of Bcl-2/Bax were markedly increased in SP600125 group(all P < 0.01). The value of AI, W/D, IAR showed significantly lower than those in I/R group (all P <0.01). Meanwhile, light morphological and ultrastructure injury were found in SP600125 group.

CONCLUSION:

SP600125 can suppress JNK signal pathway, up-regulate the ratio of Bcl-2/Bax to inhibit Caspase-3 dependent apoptosis, so that it protects lung tissue from ischemia/reperfusion injury.

• Authors: Xiao-xiao Qiu, Yong-yue Dai, Zhang-juan Song, Zhou-xi Fang, Wan-tie Wang
• Journal: Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology (Zhongguo Ying Yong Sheng Li Xue Za Zhi) Vol. 28 Issue 3 Pg. 255-8 (May 2012) ISSN: 1000-6834 [Print] China
• PMID: 22860429 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Anthracenes
• Bax protein, rat
• Proto-Oncogene Proteins c-bcl-2
• bcl-2-Associated X Protein
• pyrazolanthrone
• Casp3 protein, rat
• Caspase 3

Topics

• Animals
• Anthracenes (pharmacology)
• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Lung (blood supply, metabolism, pathology)
• MAP Kinase Signaling System
• Phosphorylation
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Rats
• Rats, Wistar
• Reperfusion Injury (metabolism, pathology)
• bcl-2-Associated X Protein (metabolism)