Intervention effect of ghrelin on nuclear factor-κB and fibrinolytic system of acute lung injury mice

Abstract

Objective To investigate the effect of ghrelin on nuclear factor-κB (NF-κB) and fibrinolytic system in acute lung injury mice induced by cecal ligation and perforation (CLP) at early stage. Methods Thirty-two Kunming mice were randomly divided into normal group, sham-operated group,CLP group and ghrelin intervention group. Ghrelin intervention group received intraperitoneal injection with ghrelin at 5 h,10 h, 15 h time points after CLP (total 40 nmol/kg). HE staining was usedfor pathological detection. The expression of NF-κB was detected by immunohistochemistry. Plasma plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA) were detected by enzyme linked immunosorbent assay,and the ratio of t-PA/PAI-1 was computed. Results ①Pathology results showed that compared with normal group and sham-operated group, part of alveolar cell structure was damaged,a great deal of inflammatory cell infiltrated, pulmonary interstitial edema was obvious, part had haemorrhage in CLP group. The pathologic'damage of pulmonary tissue reduced significantly in ghrelin intervention group. ②Immunohistochemistry results showed that compared with normal group and sham-operated group, NF-κB expression of pulmonary tissue markedly increased in CLP group. The expression of NF-κB in ghrelin intervention group was weaker than that in CLP group. ③Compared with normal group and sham-operated group, plasma PAI-1 and t-PA level increased significantly (P<0.01), t-PA/PAI-1 obviously decreased (P<0.01) in CLP group. Compared with CLP group, plasma PAI-1 significantly decreased (P<0.001), plasma t-PA slightly increased (P<0.05), and t-PA/PAI-1 significantly increased(P<0.01) in CLP group. Conclusions The fibrinolytic system is inhibited at the early stage of acute lung injury in mice. Ghrelin can reduce the expression of NF-κB in pulmonary tissue caused by CLP. Ghrelin may relieve acute lung injury induced by CLP and enhance fibrinolytic activity via NF-κB pathway. Key words: Acute lung injury; Ghrelin; Nuclear factor-κB; Plasminogen activator inhibitor-1; Tissue-type plasminogen activator