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重组白介素-1 受体拮抗剂可减轻三硝基苯磺酸诱导的大鼠慢性胰腺炎的严重程度。

Recombinant interleukin-1 receptor antagonist attenuates the severity of chronic pancreatitis induced by TNBS in rats.

机构信息

Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.

Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.

出版信息

Biochem Pharmacol. 2015 Feb 15;93(4):449-60. doi: 10.1016/j.bcp.2014.12.016. Epub 2015 Jan 3.

Abstract

Chronic pancreatitis (CP) is a common disease in the department of gastroenterology, with the main symptoms of exocrine and/or endocrine insufficiency and abdominal pain. The pathogenic mechanism of CP is still not fully clarified and the aims of treatment now are to relieve symptoms. In this study, we attempted to find a connection between interleukin-1β (IL-1β) and interleukin-1 receptor antagonist (IL-1Ra) in trinitrobenzene sulfonic acid (TNBS)-induced chronic pancreatitis, and then the therapeutic effect of recombinant IL-1Ra was also detected in the CP model. Chronic pancreatitis was induced by intraductal infusion of TNBS in SD rats followed by a consecutive administration of rIL-1Ra, and the histological changes and collagen content in the pancreas were measured, as well as the abdominal hypersensitivity. We found that rhIL-1Ra could attenuate the severity of chronic pancreatic injury, modulate the extracellular matrix secretion, focal proliferation and apoptosis, and cellular immunity in TNBS-induced CP. Interestingly, rIL-1Ra could also block the pancreatitis-induced referred abdominal hypersensitivity. In conclusion, IL-1Ra may play a protective role in CP and rIL-1Ra would be a potential therapeutic target for the treatment of CP, while its possible mechanisms and clinical usage still need further investigation.

摘要

慢性胰腺炎(CP)是消化内科的常见病,主要表现为外分泌和/或内分泌功能不全以及腹痛。CP 的发病机制尚未完全阐明,目前的治疗目标是缓解症状。在这项研究中,我们试图在三硝基苯磺酸(TNBS)诱导的慢性胰腺炎中找到白细胞介素-1β(IL-1β)和白细胞介素-1 受体拮抗剂(IL-1Ra)之间的联系,然后在 CP 模型中检测重组 IL-1Ra 的治疗效果。SD 大鼠通过胰管内输注 TNBS 诱导慢性胰腺炎,然后连续给予 rIL-1Ra,测量胰腺的组织学变化和胶原含量,以及腹部过敏反应。我们发现 rhIL-1Ra 可减轻 TNBS 诱导的慢性胰腺损伤的严重程度,调节细胞外基质分泌、局灶性增殖和细胞凋亡以及细胞免疫。有趣的是,rIL-1Ra 还可以阻断胰腺炎引起的牵涉性腹部过敏反应。总之,IL-1Ra 在 CP 中可能发挥保护作用,rIL-1Ra 可能成为 CP 治疗的潜在治疗靶点,但其可能的机制和临床应用仍需进一步研究。

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