p38MAPK信号转导通路在肢体缺血后处理减轻脑缺血再灌注损伤中的作用

发布时间：2018-03-22 09:58

  本文选题：缺血再灌注　切入点：肢体缺血后处理　出处：《桂林医学院》2014年硕士论文　论文类型：学位论文

【摘要】：目的：探讨p38MAPK信号转导通路在肢体缺血后处理减轻大鼠脑缺血再灌注损伤中的作用。方法：将大鼠随机分为假手术组(sham组)、缺血再灌注组(I/R组)、肢体缺血后处理组(LPostC组)、肢体缺血后处理+p38MAPK抑制剂SB203580组(LPostC+SB组)，线栓法建立局灶性脑缺血再灌注模型，采用双侧下肢股动脉夹闭10min、开放10min三个循环模型。缺血2h再灌注24h，进行神经功能缺损评分，HE染色观察脑组织病理形态学改变，用TUNEL法检测神经细胞凋亡，用免疫组化法观察脑组织磷酸化ATF-2表达，western blot检测大鼠额顶部脑皮质磷酸化p38MAPK蛋白含量。结果：（1）与sham组比较，I/R组大鼠出现明显神经功能缺损及脑组织缺血改变；与I/R组比较，LPostC组、LPostC+SB组神经功能缺损、脑组织缺血改变明显减轻；与LPostC组比较，LPostC+SB组脑组织缺血改变减轻。（2）与sham组比较，I/R组额顶部皮质凋亡细胞数明显增加；与I/R组比较，LPostC组、LPostC+SB组凋亡细胞显著减少；与LPostC组比较，LPostC+SB组凋亡细胞减少（均P0.05）。（3）与sham组比较，I/R组额顶部皮质磷酸化p38MAPK及磷酸化ATF-2表达明显增加；与I/R组比较，LPostC组、LPostC+SB组磷酸化p38MAPK及磷酸化ATF-2表达均显著减少；与LPostC组比较，LPostC+SB组磷酸化p38MAPK及磷酸化ATF-2表达明显减少（均P0.05）。结论：肢体缺血后处理对脑缺血再灌注损伤具有保护作用，，其机制可能与抑制p38MAPK激活，降低磷酸化ATF-2蛋白表达，从而抑制细胞凋亡有关。
[Abstract]:Objective: to investigate the role of p38MAPK signal transduction pathway in reducing cerebral ischemia-reperfusion injury in rats after limb ischemia. Methods: rats were randomly divided into sham group, ischemia reperfusion group and I / R group. The model of focal cerebral ischemia-reperfusion was established in the LPostC group, the limb ischemic p38MAPK inhibitor SB203580 group, and the LPostC SB group, the focal cerebral ischemia-reperfusion model was established by the method of thread embolization. The femoral arteries of the lower extremities were clamped for 10 minutes and the three circulatory models of 10min were opened. After 2 hours of ischemia and 24 hours of reperfusion, the pathological changes of brain tissue were observed by HE staining and the apoptosis of nerve cells was detected by TUNEL method. The expression of phosphorylated ATF-2 in brain tissue was detected by Western blot method. Results compared with sham group, there were obvious neurological deficits and cerebral ischemia changes in sham group. Compared with the I / R group, the neurological impairment and cerebral ischemia in LPostC SB group were significantly alleviated, and those in LPostC SB group were alleviated compared with that in LPostC group. (2) compared with sham group, the number of apoptotic cells in the parietal cortex of the I / R group was significantly higher than that in the sham group. Compared with the I / R group, the apoptotic cells in LPostC SB group were significantly decreased, and the expression of phosphorylated p38MAPK and phosphorylated ATF-2 in the frontal parietal cortex were significantly increased in the LPostC SB group compared with the sham group (P 0.05, P 0.05, P < 0.05), and the expression of phosphorylated ATF-2 in the frontal parietal cortex of the sham group was significantly higher than that in the sham group. Compared with I / R group, the expression of phosphorylated p38MAPK and phosphorylated ATF-2 decreased significantly in LPostC group. Compared with LPostC group, the expression of phosphorylated p38MAPK and phosphorylated ATF-2 in LPostC SB group was significantly decreased (P 0.05). Conclusion: limb ischemic post-treatment has protective effect on cerebral ischemia-reperfusion injury, which may be related to inhibition of p38MAPK activation and decrease of phosphorylated ATF-2 protein expression. It is related to inhibition of apoptosis.
【学位授予单位】：桂林医学院
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R743.3


本文编号：1648153