|Effects of peroxisome proliferator-activated receptor-beta/delta on sepsis induced acute lung injury|
|Wang Cairui; Zhou Guopeng; Zeng Zeng|
|关键词||peroxisome proliferator activated receptor acute lung injury sepsis alveolar macrophages STAT3 transcription factor|
|刊名||CHINESE MEDICAL JOURNAL|
|WOS标题词||Science & Technology|
|类目[WOS]||Medicine, General & Internal|
|研究领域[WOS]||General & Internal Medicine|
|关键词[WOS]||RESPIRATORY-DISTRESS-SYNDROME ; PPAR-DELTA ; CECAL LIGATION ; BETA-OXIDATION ; UNITED-STATES ; SEPTIC SHOCK ; LIPOPOLYSACCHARIDE ; INFLAMMATION ; MODELS ; MICE|
Background Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the first steps in the development of multiple organ failure induced by sepsis. A systemic excessive inflammatory reaction is currently the accepted mechanism of the pathogenesis of sepsis. Several studies have suggested a protective role of the peroxisome proliferator activated receptor-beta/delta (PPAR-beta/delta) in related inflammatory diseases. But the role of PPAR beta/delta in ALI remains uncertain. The aim of this study was to investigate the role and possible mechanism of PPAR beta/delta in ALI induced by sepsis.
Methods Cecal ligation and puncture (CLP) was used as a sepsis model. Rats were randomly divided into four groups, the control group (CON, n=6), sham-operation group (SHAM, n=12), cecal ligation and puncture group (CLP, n=30), GW501516 group (CLP+GW, n=25), which underwent CLP and were subcutaneously injected with the PPAR-beta/delta agonist GW501516 (0.05 mg/100 g body weight). Survival was monitored to 24 hours after operation. Blood pressure, serum creatinine, blood urea nitrogen, aspartate aminotrasferase and alanine aminotrasferase were measured after CLP. Concentrations of tumor necrosis factor a (TNF-alpha) and interleukin (IL)-1 beta in serum were detected by enzyme linked immunosorbent assay (ELISA) kits. Lung tissue samples were stained with H&E and scored according to the degree of inflammation. Bacterial colonies were counted in the peritoneal fluid. Alveolar macrophages were cultured and incubated with GW501516 (0.15 mu mol/L) and PPAR beta/delta adenovirus and then treated with Lipopolysaccharide (2 mu g/ml) for 2 hours. The TNF-alpha, IL-1 beta and IL-6 RNA in lung and alveolar macrophages were determined by real-time PCR. Phosphorylation of signal transducer and activator of transcription 3 (STAT3) in lung and alveolar macrophages was detected by Western blotting.
Results GW501516 significantly increased the survival of septic rats, decreased histological damage of the lungs, reduced inflammatory cytokines in serum and lung tissues of septic rats and did not increase counts of peritoneal bacteria. In vitro, GW501516 and over-expression of PPAR beta/delta attenuated gene expression of TNF-alpha, IL-1 beta and IL-6 in alveolar macrophages. Both in vivo and in vitro, PPAR beta/delta inhibited the phosphorylation of STAT3.
Conclusion PPAR beta/delta plays a protective role in sepsis induced ALI via suppressing excessive inflammation.
|资助机构||National Science Fund|
|作者单位||Peking Univ, Hosp 1, Dept Geriatr, Beijing 100034, Peoples R China|
|Wang Cairui,Zhou Guopeng,Zeng Zeng. Effects of peroxisome proliferator-activated receptor-beta/delta on sepsis induced acute lung injury[J]. CHINESE MEDICAL JOURNAL,2014,127(11):2129-2137.|
|APA||Wang Cairui,Zhou Guopeng,&Zeng Zeng.(2014).Effects of peroxisome proliferator-activated receptor-beta/delta on sepsis induced acute lung injury.CHINESE MEDICAL JOURNAL,127(11),2129-2137.|
|MLA||Wang Cairui,et al."Effects of peroxisome proliferator-activated receptor-beta/delta on sepsis induced acute lung injury".CHINESE MEDICAL JOURNAL 127.11(2014):2129-2137.|