[p38丝裂原活化蛋白激酶抑制剂抑制脑死亡大鼠肝脏中促炎细胞因子的表达]

[p38 mitogen-activated protein kinase inhibitor suppresses the expression of pro-inflammatory cytokines in liver from brain dead rats].

作者信息

Chen Jie, Liu Jia-wen, Zeng Hui-lan, Zeng Yao-ying, Su Ze-xuan

机构信息

Department of Organ Transplantation, First Affiliated Hospital of Jinan University, Guangzhou 510630, China.

出版信息

Zhonghua Gan Zang Bing Za Zhi. 2010 Sep;18(9):703-6. doi: 10.3760/cma.j.issn.1007-3418.2010.09.014.

DOI:10.3760/cma.j.issn.1007-3418.2010.09.014

PMID:20943085

Abstract

OBJECTIVE

To observe the suppressive effect on the expression of pro-inflammatory cytokines in liver from brain dead (BD) rats through inhibition of p38 mitogen-activated protein kinase (MAPK) signaling pathway by SB203580.

METHODS

A total of 30 male Wistar rats weighing from 180 to 200 g were randomly divided into 3 experimental groups: (1) BD group (n = 10): brain death was induced in rats; (2) BD+SB203580 group (n = 10): brain death was successfully induced and SB203580 (10 mg/kg) was given through dorsal vein of penis. After brain death artificial ventilation was maintained for 6 hours and only those with mean arterial blood pressure more than 80 mm Hg (1 mm Hg = 0.133 kPa) were accepted as BD donors. (3) Control group (n = 10): living healthy rats. The expressions of TNFalpha and IL-1beta mRNA in liver tissues were analyzed by RT-PCR and the protein expressions of TNFalpha, IL-1beta and phosphorylated p38MAPK were detected by Western blot.

RESULTS

The phosphorylated p38MAPK detected in the liver in BD group was significantly increased compared with the control group (q = 172.53, P < 0.01), and the expressions of TNFalpha and IL-1beta mRNA and proteins in liver were also significantly increased in BD group compared with the control group (q = 123.99, 135.35, 243.09 and 192.23, respectively, P < 0.01). The phosphorylated p38MAPK was decreased in BD+SB203580 group and significantly decreased compared with the BD group (q = 63.90, P is less than 0.05), but higher than that in control group (q = 108.63, P < 0.01). The expressions of TNFalpha and IL-1beta mRNA and proteins in liver were significantly decreased in BD+SB203580 group compared with the BD group (q = 55.11, 98.13, 61.03 and 50.85, respectively, P < 0.01), but higher than that in control group (q = 68.89, 37.22, 182.06 and 141.38, respectively, P < 0.01). SB203580 can suppress the expression of pro-inflammatory cytokines in the liver of brain dead rats through the inhibition of p38MAPK signaling pathway which may reduce the immunogenicity of donor livers.

摘要

目的

通过SB203580抑制p38丝裂原活化蛋白激酶（MAPK）信号通路，观察其对脑死亡（BD）大鼠肝脏中促炎细胞因子表达的抑制作用。

方法

选取30只体重180～200 g的雄性Wistar大鼠，随机分为3个实验组：（1）BD组（n = 10）：诱导大鼠脑死亡；（2）BD+SB203580组（n = 10）：成功诱导脑死亡后，经阴茎背静脉给予SB203580（10 mg/kg）。脑死亡后维持人工通气6小时，仅将平均动脉血压高于80 mmHg（1 mmHg = 0.133 kPa）的大鼠作为BD供体。（3）对照组（n = 10）：健康存活大鼠。采用RT-PCR分析肝组织中TNFα和IL-1β mRNA的表达，采用蛋白质印迹法检测TNFα、IL-1β和磷酸化p38MAPK的蛋白表达。

结果

BD组肝脏中检测到的磷酸化p38MAPK较对照组显著升高（q = 172.53，P < 0.01），BD组肝脏中TNFα和IL-1β mRNA及蛋白表达较对照组也显著升高（q分别为123.99、135.35、243.09和192.23，P < 0.01）。BD+SB203580组磷酸化p38MAPK降低，与BD组相比显著降低（q = 63.90，P < 0.05），但高于对照组（q = 108.63，P < 0.01）。BD+SB203580组肝脏中TNFα和IL-1β mRNA及蛋白表达较BD组显著降低（q分别为55.11、98.13、61.03和50.85，P < 0.01），但高于对照组（q分别为68.89、37.22、182.06和141.38，P < 0.01）。SB203580可通过抑制p38MAPK信号通路抑制脑死亡大鼠肝脏中促炎细胞因子的表达，这可能降低供肝的免疫原性。