摘要
目的探讨p38丝裂素活化蛋白激酶(p38MAPK)在新生大鼠高氧肺损伤中的表达及其特异性抑制剂SB203580,对其产生保护作用的机制。方法160只新生大鼠随机分为空气对照组、高氧肺损伤组、高氧肺损伤+SB203580组和高氧肺损伤+生理盐水组,建立模型。作用12、24、72h和1周后,分别处死大鼠。取右上肺进行肺组织病理学检查,取右下肺进行肺湿/干重比值(W/D)测定,取左肺以Western免疫印迹法检测肺组织中p38MAPK的表达,以酶联免疫吸附试验检测肺组织中TGF-β1的含量。结果72h时,高氧肺损伤组和高氧肺损伤+生理盐水组p38MAPK呈强阳性表达;在这两组中,肺组织TGF-β1浓度随时间延长呈持续上升趋势,在各时相点均明显高于空气对照组和高氧肺损伤+SB203580组(P均<0.01)。结论p38MAPK参与了新生大鼠高氧肺损伤的过程,SB203580能够通过阻断p38MAPK表达,进而抑制TGF-β1表达来减轻这种损伤。
Objective To investigate the expression of p38MAPK and the mechanism of lung protective effect of its specific inhibitor SB203580 in newborn rats with hyperoxia induced lung injury. Methods One hundred and sixty newborn rats were divided randomly into 4 group： Ⅰ air control group, Ⅱ hyperoxia induced lung injury group, Ⅲ hyperoxia induced lung injury ＋ SB203580 group （intraperitoneal injection at 5 mg/kg, 1/d, totally 3 days） and Ⅳ hyperoxia induced lung injury ＋ Sodium Chloride group. Group Ⅱ ,Ⅲ and Ⅳ were exposured to hyperxia （ 〉95% ） for 72 h, at the same time, group Ⅰ were fed in normal air. The rats were sacrificed 12 h, 24 h, 72 h and 1 week after hyperoxia and SB203580 treatment. Right upper lobe of lungs were harvested for histopathologic study, right lower lobe of lungs were harvested for measurement of wet/dry weight （W/D） ratio and left lung were harvested for measurement of expression of p38MAPK by Western blot and TGF-β1 concentration by ELISA. Results The expression of p38MAPK was strongly positive in hyperoxia group and hyperoxia ＋ Sodium Chloride group at 72 hours. In these groups, the concentration of TGF-β1 increased significantly with time. lasting and their concentrations were higher than those in the air control group and hyperoxia ＋ SB203580 group at each time point （P 〈 0. 01 ）. Conclusions p38MAPK is involved in the process of hyperoxia induced lung injury. The lung injury can be relieved by administering SB203580 which blocks the expression of p38MAPK, then. inhibiting the expression of TGF-β1.
出处
《中国新生儿科杂志》
CAS
2007年第3期153-156,共4页
Chinese Journal of Neonatology
关键词
高氧症
肺
基因
Hyperoxia
Lung
Genes
