Ghrelin Attenuates Sepsis-Associated Acute Lung Injury Oxidative Stress in Rats
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This study investigated the effect of ghrelin on oxidative stress in septic rat lung tissue. Male Sprague-Dawley rats were divided into sham-operation, sepsis, and ghrelin groups. Sepsis was induced by cecal ligation and puncture. Ghrelin was administered intraperitoneally at 3 and 15 h post-operation. Bronchoalveolar lavage was performed to collect alveolar macrophages (AMs). Inducible nitric oxide synthase (iNOS) messenger RNA (mRNA) expression in alveolar macrophages and iNOS protein levels were measured by reverse transcription PCR (RT-PCR) and Western blot. Pulmonary pathology was analyzed and nitrotyrosine expression was examined by immunohistochemistry. Plasma superoxide dismutase (SOD) and lung wet/dry weight were measured. In the sepsis group, iNOS mRNA expression in AMs was 1.33 ± 0.05, 1.44 ± 0.08, and 1.57 ± 0.11 at 6, 12, and 20 h post-surgery, respectively, and were higher compared with the sham-operation group (p < 0.05). No increase was observed at longer time points. iNOS mRNA expression in the sepsis group was lower compared with the ghrelin group (2.27 ± 0.37) (p < 0.05) at 20 h post-surgery. iNOS protein levels in the ghrelin group (0.87 ± 0.03, p < 0.05) were lower than in the sepsis group at 20 h. Ghrelin group pathological scores were lower than in the sepsis group (p < 0.05). Plasma SOD was slightly non-significantly decreased in the ghrelin group. No difference was observed in lung wet/dry weight ratios between sepsis and ghrelin groups. iNOS mRNA expression in AMs was elevated between 6 and 20 h after cecal ligation and puncture (CLP), but did not progress. Ghrelin attenuated pulmonary iNOS protein expression and tended to increase plasma SOD activity. Ghrelin suppressed pulmonary nitrosative stress in septic rats, but did not improve lung wet/dry weight ratios.
KEY WORDSghrelin oxidative stress acute lung injury sepsis
Mian Zeng, guarantor of the entire manuscript, conceived the study, participated in its design, and drafted the manuscript. Wanmei He carried out operation on animals, samples detection, and drafted the manuscript. Lijun Li helped to translate the manuscript. Bin Li participated in the collection of samples. Liang Luo and Weiling Chen participated in the blood sample collection. Xubin Huang and Kaipan Guan performed the statistical analysis. All authors read and approved the final manuscript.
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