Chen Xu-lin, Xia Zhao-fan, Wei Duo, Ben Dao-feng, Wang Yong-jie, Wang Chang-rong, Deng Nian-qing
Department of Burns, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, P.R. China.
Zhonghua Shao Shang Za Zhi. 2005 Dec;21(6):418-21.
To investigate The modulating role of p38 mitogen-activated protein kinase (MAPK) in the expression of tumor necrosis factor-alpha in hepatic cells and its role in hepatic injury in severely burned rats.
Twenty-four adult healthy male SD rats were randomly divided into three groups (8 rats in each group): sham group, burn group, and burn with SB203580 group. A rat model of full-thickness burn injury covering 30% total body surface area (TBSA) was reproduced. The specific inhibitor of p38MAPK (SB203580 in 10 mg/kg) was given to the rats in the burn with SB203580 group at 15 minutes and 12 hours after burn. The serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured at 24 postburn hours (PBHs). The TNF-alpha mRNA expression in the liver was determined by real-time reverse transcription polymerase chain reaction, and the expression levels of p38MAPK and phosphor-p38MAPK in the liver were determined by Western blot analysis.
The serum levels of AST and ALT, and the expression of TNF-alpha mRNA in liver cells were significantly higher in burn group than those in sham and SB203580 groups (P < 0.05 or 0.01), but there was no difference between the two latter groups. It was indicated by Western blot results that there was no difference of p38MAPK expression in rat liver among the three groups (P > 0.05). The phospho-p38MAPK expression ratio among sham, burn and burn with SB203580 groups was 1.00:3.90:1.10. The phospho-p38MAPK expression was significantly lower in burn with SB203580 group than that in burn group (P < 0.01), but there was no significant difference compared with that in sham group (P > 0.05).
The postburn activated p38MAPK in rat liver after severe burn injury enhances the expression of TNF-alpha mRNA and participates in the development of postburn hepatic injury.
探讨p38丝裂原活化蛋白激酶（MAPK）对肝细胞中肿瘤坏死因子-α表达的调节作用及其在严重烧伤大鼠肝损伤中的作用。
将24只成年健康雄性SD大鼠随机分为三组（每组8只）：假手术组、烧伤组、烧伤+SB203580组。复制30%总体表面积（TBSA）的全层烧伤大鼠模型。烧伤+SB203580组大鼠在烧伤后15分钟和12小时给予p38MAPK特异性抑制剂SB203580（10 mg/kg）。在烧伤后24小时（PBHs）测量血清天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）水平。采用实时逆转录聚合酶链反应测定肝脏中TNF-α mRNA表达，采用蛋白质印迹分析测定肝脏中p38MAPK和磷酸化p38MAPK的表达水平。
烧伤组血清AST、ALT水平及肝细胞中TNF-α mRNA表达均显著高于假手术组和烧伤+SB203580组（P＜0.05或0.01），而后两组间无差异。蛋白质印迹结果显示，三组大鼠肝脏中p38MAPK表达无差异（P＞0.05）。假手术组、烧伤组、烧伤+SB203580组磷酸化p38MAPK表达比值为1.00∶3.90∶1.10。烧伤+SB203580组磷酸化p38MAPK表达显著低于烧伤组（P＜0.01），与假手术组比较无显著差异（P＞0.05）。
严重烧伤后大鼠肝脏中活化的p38MAPK增强了TNF-α mRNA的表达，并参与烧伤后肝损伤的发生发展。
