Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China.
Department of Oncology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China.
Mol Med Rep. 2019 May;19(5):3449-3458. doi: 10.3892/mmr.2019.10049. Epub 2019 Mar 18.
The present study aimed to investigate the effect of carbon monoxide (CO)‑releasing molecule‑2 (CORM‑2) on pancreatic function in sepsis‑model mice. To perform the present investigation, mice were rendered septic by cecal ligation and puncture (CLP). Then, mice were either treated with or without CORM‑2 (8 mg/kg, intravenous) for different durations (6, 12 and 24 h) immediately following CLP. The levels of serum amylase and lipase, tumor necrosis factor α, interleukin‑1β and interleukin‑6 in addition to myeloperoxidase (MPO) activity in pancreatic tissues were determined at 6, 12 and 24 h post‑CLP. Histological scores and the expression of intercellular adhesion molecule 1 (ICAM‑1), vascular cell adhesion molecule 1 (VCAM‑1), nuclear factor‑κB (NF‑κB) and phosphorylated inhibitor of κB (p‑IκB‑α) in the pancreas were also evaluated at 24 h post‑CLP. The results of the present study revealed that compared with CLP‑alone group, CORM‑2 treatment significantly (P<0.05) reduced the levels of serum amylase, lipase and pro‑inflammatory cytokines. In parallel, the severity of pancreatic histology, MPO activity and the expression levels of ICAM‑1 and VCAM‑1 in the pancreas of CORM‑2 treated CLP mice were substantially decreased compared with the untreated group. Furthermore, CORM‑2 treatment inhibited the expression levels of NF‑κB and P‑IκB‑α in the pancreas of mice following CLP compared with the untreated group. CORM‑2‑liberated CO exerted protective effects on the pancreatic function of septic mice, and the beneficial effects may be due to the suppression of NF‑κB activation and subsequent regulation of NF‑κB‑dependent expression of cytokines.
本研究旨在探讨一氧化碳（CO）释放分子-2（CORM-2）对脓毒症模型小鼠胰腺功能的影响。为进行本研究，通过盲肠结扎和穿刺（CLP）使小鼠发生脓毒症。然后，在 CLP 后立即给予或不给予 CORM-2（8mg/kg，静脉内）不同时间（6、12 和 24h）。在 CLP 后 6、12 和 24h 时测定血清淀粉酶和脂肪酶、肿瘤坏死因子-α、白细胞介素-1β和白细胞介素-6以及胰腺组织髓过氧化物酶（MPO）活性。在 CLP 后 24h 时还评估了胰腺组织中细胞间黏附分子 1（ICAM-1）、血管细胞黏附分子 1（VCAM-1）、核因子-κB（NF-κB）和磷酸化的 IκB-α（p-IκB-α）的表达以及组织学评分。本研究结果表明，与 CLP 组相比，CORM-2 治疗显著（P<0.05）降低了血清淀粉酶、脂肪酶和促炎细胞因子水平。平行地，与未处理组相比，CORM-2 处理的 CLP 小鼠胰腺组织中胰腺组织学严重程度、MPO 活性以及 ICAM-1 和 VCAM-1 的表达水平显著降低。此外，与未处理组相比，CORM-2 处理抑制了 CLP 后小鼠胰腺中 NF-κB 和 P-IκB-α的表达水平。CORM-2 释放的 CO 对脓毒症小鼠的胰腺功能具有保护作用，其有益作用可能是由于抑制了 NF-κB 的激活以及随后对 NF-κB 依赖性细胞因子表达的调节。
