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白细胞介素-11 可保护小鼠肝脏免受热缺血/再灌注(WI/Rp)损伤。

Interleukin-11 protects mouse liver from warm ischemia/reperfusion (WI/Rp) injury.

机构信息

Laboratory of Liver Transplantation, Nanjing Medical University, Nanjing, China.

Department of Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, 210029 Nanjing, China.

出版信息

Clin Res Hepatol Gastroenterol. 2016 Nov;40(5):562-570. doi: 10.1016/j.clinre.2015.11.009. Epub 2016 Mar 23.

Abstract

BACKGROUND

IL-11 is a multifunctional cytokine that belongs to the IL-6 family. Previous studies have demonstrated that IL-11 has underlying anti-inflammatory and anti-apoptotic properties. In this study, we evaluated the potential effects of IL-11 on mouse liver WI/Rp injury.

METHODS

For in vivo experiments, mice were randomly divided into four main experimental groups (n=5 each): (1) normal group - anesthesia; (2) sham group- laparotomy; (3) I/R group- liver WI/Rp; and (4) IL-11 pretreatment (500μg/kg, tail vein injection) group- administration of RhIL-11 2h before liver WI/Rp induced in the same manner as in group 3. For in vitro experiments, cells were divided into two groups: (1) H/R group- H/R; and (2) IL-11 pretreatment group- pretreatment with RhIL-11 (2μg/mL for 12h) before the induction of H/R. For both groups, three periods of reoxygenation were examined (2h, 6h, and 12h).

RESULTS

In the in vivo experiments, IL-11 protected mouse livers from WI/Rp by reducing liver enzyme levels and cellular degeneration. In the in vitro experiments, IL-11 significantly reduced hepatocyte apoptosis. In both the in vivo and in vitro experiments, IL-11 pre-treatment significantly reduced the expression of TNF-α and IL-1β. In addition, NF-κB, a target of IL-11, was suppressed in macrophages after IL-11 pre-treatment.

CONCLUSIONS

Pre-treatment with IL-11 protects mouse livers from WI/Rp injury by suppressing NF-kB activity.

摘要

背景

IL-11 是一种多功能细胞因子,属于 IL-6 家族。先前的研究表明,IL-11 具有潜在的抗炎和抗凋亡作用。在这项研究中,我们评估了 IL-11 对小鼠肝 WI/Rp 损伤的潜在影响。

方法

对于体内实验,将小鼠随机分为四个主要实验组(每组 5 只):(1)正常组-麻醉;(2)假手术组-剖腹术;(3)I/R 组-肝 WI/Rp;和(4)IL-11 预处理(500μg/kg,尾静脉注射)组-以与组 3 相同的方式在肝 WI/Rp 前 2 小时给予 RhIL-11。对于体外实验,细胞分为两组:(1)H/R 组-H/R;和(2)IL-11 预处理组-在诱导 H/R 前用 RhIL-11(2μg/mL,12 小时)预处理。对于两组,均检查三个复氧期(2h、6h 和 12h)。

结果

在体内实验中,IL-11 通过降低肝酶水平和细胞变性来保护小鼠肝脏免受 WI/Rp 的损伤。在体外实验中,IL-11 显著减少了肝细胞凋亡。在体内和体外实验中,IL-11 预处理均显著降低了 TNF-α和 IL-1β的表达。此外,IL-11 预处理后巨噬细胞中 NF-κB,IL-11 的靶标,受到抑制。

结论

IL-11 预处理通过抑制 NF-κB 活性来保护小鼠肝脏免受 WI/Rp 损伤。

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