Ghrelin regulates sepsis‑induced rat acute gastric injury

Abstract

Ghrelin, a peptide expressed in the gastric mucosa, has an essential role in sustaining the normal function of the digestive system. Sepsis is one of the primary causes of mortality in intensive care units and can lead to multiple organ dysfunction, especially in the gastrointestinal system. The aim of the present study was to explore the effect of ghrelin on gastric blood flow in a rat model of sepsis, as well as the effect of ghrelin on the expression of the apoptotic markers, B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (Bax), in gastric tissues. The sepsis model was established using cecal ligation and puncture (CLP). The expression levels of apoptosis-related factors in gastric epithelial cell were determined by immunohistochemistry, reverse transcription quantitative-PCR and western blotting. Collectively, the present results suggested that ghrelin administration attenuated sepsis symptoms induced by CLP. Blood flow in the stomach greater curvature was significantly higher in the CLP-induced sepsis group rats (284.3±95.7 perfusion units) compared with the sham operation group (317.8±5.2 perfusion units; P<0.05), whereas there was no difference between the CLP group treated with ghrelin (377.8±99.0 perfusion units) and the sham rats. Ghrelin administration also reduced the secretion of pro-inflammatory cytokines compared with the CLP-induced sepsis group rats. In addition, CLP significantly reduced the expression of Bcl-2 and enhanced the expression of the pro-apoptotic proteins, Bax and cleaved caspase-3; whereas, ghrelin application reversed the effects of CLP on these apoptosis-associated proteins. In conclusion, the present study revealed that ghrelin has the ability to increase blood flow in the gastrointestinal tract in a sepsis model and can also regulate the expressions of apoptosis-associated factors in gastric tissues. These results suggest that ghrelin could be a novel treatment for sepsis-induced gastric injury.

Ghrelin as an Anti-Sepsis Peptide: Review

“…In another rat model, treatment with ghrelin after CLP increased the expression of autophagy-associated proteins. This further supports that ghrelin protects intestinal mucosa from sepsis injury ( 117 – 121 ).…”

“…In a CLP-induced septic mouse model, administration of ghrelin decreased weight loss and intestinal mucosal damage by reducing inflammatory responses. It also improved the function of intestinal epithelial cells of rats ( 117 ). In another rat model, treatment with ghrelin after CLP increased the expression of autophagy-associated proteins.…”

“…Ghrelin administration in a mouse model induced angiogenesis and neurogenesis in the hippocampus (136). After CLP in rats, FIGURE 3 | Ghrelin and its effect on various organs during sepsis (110)(111)(112)(113)(114)(115)(116)(117)(118)(119)(120)(121)(122)(123)(124)(125)(126).…”

Ghrelin attenuates infectious bursal disease virus–induced early inflammatory response and bursal injury in chicken

“…In mammals, a number of studies demonstrated that ghrelin alleviated organ injury in different disease models. For example, ghrelin protected the heart against ischemia/reperfusion injury ( Wang et al., 2017 ), ameliorated acute lung injury after hemorrhagic shock ( Zhang et al., 2019 ), and regulated sepsis-induced rat acute gastric injury ( Li et al., 2019 ). Our results indicated that ghrelin could protect the chicken bursa from damage similar to that of mammals through decreasing the production of cytokines in the bursa evoked by IBDV.…”