小鼠脑缺血再灌注后蛇床子素对心肺组织氧化应激反应的影响

发布时间：2018-06-20 22:43

本文选题：蛇床子素 + 脑缺血再灌注　；参考：《河北医科大学》2017年硕士论文

【摘要】：脑缺血再灌注后会引起多器官损伤,其机制复杂,氧化应激反应是引发早期损伤的重要途径之一。蛇床子素(Osthole,OST)属于天然香豆素类化合物,前期实验研究发现,蛇床子素对脑缺血再灌注引起的多器官损伤有保护功效,此结果是否通过氧化应激途径发挥作用,是本课题研究的主要内容。目的:在全脑缺血再灌注小鼠模型上,观察蛇床子素对心肺组织氧化应激指标的影响,分析其保护作用机制。方法:采用改进的Himori法暂时性阻断两侧颈总动脉制备小鼠脑缺血再灌注损伤的模型,50只小鼠,随机分为5组,分别为假手术组(进行手术,但不进行脑缺血再灌注)、模型组(即脑缺血再灌注组)、蛇床子素高剂量组、中剂量组和低剂量组,高、中、低剂量组于缺血前30min分别腹腔注射(ip)蛇床子素10 mg·kg~(-1),1.0 mg·kg~(-1),0.1mg·kg~(-1);假手术组与模型组分别ip等体积溶剂l0ml·kg~(-1)(按N,N-二甲基甲酰胺:吐温80:生理盐水等于1:1:8配制)。应用生化试验盒检测小鼠心肺组织及血浆中超氧化物歧化酶(superoxide dismutase,SOD);过氧化氢酶(catalase,CAT);谷胱甘肽过氧化物酶(glutathioneperoxidase,GSH-PX)的活性及丙二醛(malondialdehyde,MDA)的含量,统计分析上述指标变化。结果:1脑缺血再灌注小鼠心肌组织内GSH-PX,SOD,CAT活性和MDA含量变化与假手术组比较,模型组小鼠心肌内GSH-PX、CAT、SOD活性显著降低(P0.01),MDA含量显著增高(P0.01);与模型组比较,蛇床子素组的GSH-PX、SOD活性均显著提高(高剂量组P0.01,中、低剂量组P0.05),CAT活性明显提高(高剂量组P0.01,中剂量组P0.05),MDA含量显著降低(高剂量组P0.01,中、低剂量组P0.05)。2脑缺血再灌注小鼠肺组织内GSH-PX,SOD,CAT活性和MDA含量变化与假手术组比较,模型组小鼠的GSH-PX,SOD,CAT活性显著降低(P0.01),MDA含量显著增高(P0.01);与模型组比较,蛇床子素组GSH-PX活性明显提高(高剂量组P0.01,中剂量组P0.05),CAT、SOD活性明显提高(高剂量组P0.01,中、低剂量组P0.05),MDA含量显著降低(高剂量组P0.01,中、低剂量组P0.05)。3脑缺血再灌注小鼠血液内GSH-PX,SOD,CAT活性和MDA含量变化与假手术组比较,模型组小鼠的GSH-PX,SOD,CAT活性显著降低(P0.01),MDA含量显著增高(P0.01);与模型组比较,蛇床子素组GSH-PX、CAT、SOD活性明显提高(高剂量组P0.01,中剂量组P0.05),MDA含量显著降低(高剂量组P0.01,中剂量组P0.05)。结论:脑缺血再灌注模型小鼠,其心肌组织、肺和血液中GSH-PX,SOD,CAT的活力明显下降,MDA的含量显著增高,出现明显的氧化应激反应;蛇床子素可显著改善此种氧化应激反应,提示对脑缺血再灌注后的心肺组织起到保护作用。
[Abstract]:The mechanism of multiple organ damage induced by cerebral ischemia and reperfusion is complicated. Oxidative stress is one of the important ways to induce early injury. Ostholein OST is a natural coumarin compound. Previous studies have found that osthol has protective effect on multiple organ damage induced by cerebral ischemia-reperfusion, and whether this effect can be played by oxidative stress pathway. It is the main content of this research. Aim: to observe the effect of osthol on oxidative stress index of heart and lung tissue and analyze the protective mechanism of osthol on global cerebral ischemia reperfusion mice model. Methods: a total of 50 mice with cerebral ischemia-reperfusion injury were established by temporary occlusion of bilateral common carotid arteries by modified Himori method. But without cerebral ischemia-reperfusion, the model group (i.e. cerebral ischemia-reperfusion group, high dose group, middle dose group and low dose group, high and medium dose group), In the low dose group, 30min was injected intraperitoneally before ischemia, the osthol 10 mg 路kg ~ (-1) ~ (-1) was 1.0 mg 路kg ~ (-1), the sham operation group and the model group were given IP equal volume solvent l0ml ~ (1) ~ (-1) (according to NN-dimethylformamide: Tween 80: normal saline = 1:1:8), the rats in the sham operation group and the model group were prepared with iso-volume solvent (NN-dimethylformamide: Tween-80: normal saline = 1:1:8). The activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX) and malondialdehyde (malondialdehyde) (MDAs) in heart and lung tissues and plasma of mice were detected by biochemical test box. Results compared with the sham operation group, the activity of GSH-PXX SODX cat and the content of MDA in the myocardial tissue of mice with cerebral ischemia and reperfusion were significantly decreased in the model group compared with that in the sham operation group, and the content of MDA in the myocardium of the model group was significantly lower than that of the model group, and compared with the model group, the activity of GSH-PXX CATO SOD in the model group was significantly lower than that in the model group. The activity of GSH-PXO SOD in the osthol group was significantly increased (P 0.01 in high dose group, P0.05 cat activity in low dose group (P 0.01 in high dose group, P 0.05 in middle dose group, P 0.01 in high dose group, P 0.01 in middle dose group, P 0.01 in high dose group, P 0.01 in middle dose group, P 0.01 in high dose group, P 0.01 in middle dose group). Compared with sham-operated group, the activity of GSH-PXX SODX cat and the content of MDA in lung tissue of low dose group P0.05n.2 mice with cerebral ischemia-reperfusion increased significantly compared with those of sham operation group, and the activity of GSH-PXX SODX cat increased significantly compared with model group, and compared with model group, the activity of GSH-PXX SODX cat in model group increased significantly than that in model group. The activity of GSH-PX in osthol group was significantly increased (P 0.01 in high dose group and CAT SOD activity in medium dose group was significantly increased (P 0.01 in high dose group, P 0.05 in medium dose group, P 0.05 in low dose group, P 0.01 in high dose group, in medium dose group, P 0.01 in medium dose group). Compared with the sham-operated group, the activity of GSH-PXX SODX cat and the content of MDA in the blood of the low dose group P0.050.3.Compared with the sham operation group, the activity of GSH-PXX SODD-cat decreased significantly in the model group, and the content of MDA in the model group was significantly higher than that in the model group, and compared with the model group, the activity of GSH-PXX SODX cat in the model group was significantly higher than that in the model group. The activity of SOD was significantly increased in osthol group (P0.01 in high dose group and P0.05 in middle dose group (P0.01 in high dose group and P0.05 in middle dose group). Conclusion: the activity of GSH-PXX SODD-cat in myocardial tissue, lung and blood of cerebral ischemia-reperfusion model mice is obviously decreased, the content of MDA is significantly increased and the oxidative stress response is obvious, and osthol can significantly improve the oxidative stress response. The results suggest that it can protect the cardiopulmonary tissue after cerebral ischemia and reperfusion.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R285.5

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