Chen Jie, Liu Jia-wen, Zeng Hui-lan, Zeng Yao-ying, Su Ze-xuan
Department of Organ Transplantation, First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
Zhonghua Gan Zang Bing Za Zhi. 2010 Sep;18(9):703-6. doi: 10.3760/cma.j.issn.1007-3418.2010.09.014.
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.
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.
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.
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。
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。
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。
