Liu Ying, Liao Ribin, Qiang Zhanrong, Zhang Cheng
Department of Gastroenterology, The Second Affiliated Hospital of Guilin Medical University, Guilin 541000, People's Republic of China
Department of Gastroenterology, The Second Affiliated Hospital of Guilin Medical University, Guilin 541000, People's Republic of China.
Biosci Rep. 2017 Apr 28;37(2). doi: 10.1042/BSR20160483. Print 2017 Apr 30.
Severe acute pancreatitis (SAP) is a disease usually associated with systemic organ dysfunction or pancreatic necrosis. Most patients with SAP suffer from defective intestinal motility in the early phase of the disease. Additionally, SAP-induced inflammation produces hydrogen sulphide (HS) that impairs the gastrointestinal (GI) system. However, the exact mechanism of HS in the regulation of SAP is yet to be elucidated. In the present paper, we used a rat model of SAP to evaluate the role of HS on intestinal motility by counting the number of bowel movements and investigating the effect of HS on inflammation. We treated colonic muscle cells (CMCs) with SAP plasma, tumour necrosis factor-α (TNF-α) or interleukin-6 (IL-6) and measured the expressions of HS-producing enzymes cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS) and and PI3K/Akt by using quantitative PCR, Western blotting and immunohistochemical detection. We used the PI3K inhibitor LY294002 and the siRNA si- to suppress the activity of the PI3K/Akt/ signalling pathway. We found that, in the SAP rat model, HS facilitated an inhibitory effect on intestinal motility and enhanced the inflammatory response caused by SAP (<0.05). The expressions of CSE and CBS in CMCs were significantly increased after treatment with TNF-α or IL-6 (<0.05). Blocking the PI3K/Akt/ pathway remarkably inhibited the synthesis of CSE and CBS. Our data demonstrated that HS plays a vital role in the pathogenesis of SAP and that SAP is modulated by inflammation driven by the PI3K/Akt/ signalling pathway.
重症急性胰腺炎（SAP）是一种通常与全身器官功能障碍或胰腺坏死相关的疾病。大多数SAP患者在疾病早期存在肠道动力障碍。此外，SAP引发的炎症会产生硫化氢（HS），损害胃肠（GI）系统。然而，HS在SAP调节中的具体机制尚待阐明。在本研究中，我们使用SAP大鼠模型，通过计算排便次数评估HS对肠道动力的作用，并研究HS对炎症的影响。我们用SAP血浆、肿瘤坏死因子-α（TNF-α）或白细胞介素-6（IL-6）处理结肠肌细胞（CMCs），并通过定量PCR、蛋白质印迹和免疫组化检测来测量产HS酶胱硫醚-γ-裂解酶（CSE）、胱硫醚-β-合酶（CBS）以及PI3K/Akt的表达。我们使用PI3K抑制剂LY294002和小干扰RNA（siRNA）抑制PI3K/Akt/信号通路的活性。我们发现，在SAP大鼠模型中，HS对肠道动力有抑制作用，并增强了SAP引起的炎症反应（<0.05）。用TNF-α或IL-6处理后，CMCs中CSE和CBS的表达显著增加（<0.05）。阻断PI3K/Akt/信号通路可显著抑制CSE和CBS的合成。我们的数据表明，HS在SAP发病机制中起重要作用，且SAP受PI3K/Akt/信号通路驱动的炎症调节。
