Department of General Surgery, The Second Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
Department of Intensive Medicine, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
Mol Med Rep. 2019 Jun;19(6):5424-5432. doi: 10.3892/mmr.2019.10208. Epub 2019 Apr 30.
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.
胃饥饿素是一种在胃黏膜中表达的肽，在维持消化系统的正常功能方面起着至关重要的作用。脓毒症是重症监护病房（ICU）患者死亡的主要原因之一，可导致多器官功能障碍，尤其是在胃肠道系统。本研究旨在探讨胃饥饿素对脓毒症大鼠模型胃血流的影响，以及胃饥饿素对胃组织中凋亡标志物 B 细胞淋巴瘤 2（Bcl-2）和 Bcl-2 相关 X（Bax）表达的影响。采用盲肠结扎穿孔（CLP）建立脓毒症模型。通过免疫组织化学、逆转录定量聚合酶链反应和蛋白质印迹法测定胃上皮细胞中凋亡相关因子的表达水平。研究结果表明，胃饥饿素给药可减轻 CLP 诱导的脓毒症症状。CLP 诱导的脓毒症组大鼠胃大弯血流量（284.3±95.7 灌注单位）明显低于假手术组（317.8±5.2 灌注单位；P<0.05），而给予胃饥饿素的 CLP 组（377.8±99.0 灌注单位）与假手术大鼠之间无差异。与 CLP 诱导的脓毒症组大鼠相比，胃饥饿素给药还减少了促炎细胞因子的分泌。此外，CLP 显著降低了 Bcl-2 的表达，并增强了促凋亡蛋白 Bax 和 cleaved caspase-3 的表达；而胃饥饿素的应用则逆转了 CLP 对这些凋亡相关蛋白的影响。综上所述，本研究表明，胃饥饿素具有增加脓毒症模型胃肠道血流的能力，还可以调节胃组织中与凋亡相关的因子表达。这些结果提示胃饥饿素可能成为治疗脓毒症诱导的胃损伤的一种新方法。
