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目的研究浸水束缚(WIR)应激大鼠胃黏膜p38MAPK信号转导级联的活化情况及氧自由基对其的影响。方法雄性SD大鼠随机分为对照组(n=10)、WIR应激模型组(n=50)和Tempol预处理组(n=20)。采用浸水束缚应激方法复制大鼠应激性溃疡损伤模型,术前1h按分组情况给予或不给予氧自由基清除剂Tempol。WIR应激模型组动物于应激后0、5、15、30、45、90、180、360min分批处死,Tempol处理组动物于应激30min和360min处死取材,Westernblot法检测胃黏膜p38MAPK活化情况,并检测胃黏膜组织丙二醛(MDA)活性和促炎性细胞因子的表达情况。结果胃黏膜组织p38MAPK在应激后15min即开始活化,90min达高峰并且持续活化到应激后360min。提前给予Tempol后抑制了p38MAPK活化,应激后30min及360min大鼠胃黏膜p38MAPK活化水平Tempol处理组(分别为0.77±0.24、0.58±0.12)明显低于模型组(分别为1.22±0.16、1.73±0.09,P<0.05),且MDA活性和促炎性细胞因子TNF-α、IL-1β、CINC-1的mRNA表达都受到抑制。结论氧自由基介导的p38MAPK活化在浸水束缚应激后早期大鼠胃黏膜损伤中具有重要作用,清除氧自由基可预防和治疗应激后胃黏膜损伤。
Objective To investigate the activation of p38 MAPK signal transduction cascade in gastric mucosa of rats exposed to water immersion (WIR) and the effect of oxygen free radicals on it. Methods Male SD rats were randomly divided into control group (n = 10), WIR stress model group (n = 50) and Tempol pretreatment group (n = 20). The model of stress ulcer injury was induced by water immersion and restraint stress method. The oxygen free radical scavenger Tempol was given or not given by grouping 1h before operation. Animals in WIR stress group were sacrificed at 0, 5, 15, 30, 45, 90, 180, 360min after stress. Animals in Tempol group were sacrificed at 30min and 360min. Western blotting was used to detect the activation of p38MAPK in gastric mucosa. , And detected the malondialdehyde (MDA) activity and the expression of proinflammatory cytokines in gastric mucosa. Results The gastric mucosal tissue p38MAPK started to activate at 15 min after stress, peaked at 90 min and continued to activate at 360 min after stress. Pretreatment with Tempol inhibited the activation of p38MAPK. The levels of p38MAPK in gastric mucosa of Tempol-treated group (0.77 ± 0.24 and 0.58 ± 0.12, respectively) at 30 min and 360 min after stress were significantly lower than those in model group (1.22 ± 0.16 and 1.73 ± 0.09, P <0.05), and the MDA activity and the mRNA expression of proinflammatory cytokines TNF-α, IL-1β and CINC-1 were all inhibited. Conclusion Oxygen free radical-mediated activation of p38MAPK plays an important role in the early gastric mucosal injury induced by water immersion and restraint stress. Scavenging oxygen free radicals can prevent and treat gastric mucosal injury after stress.