本文選題：蛇床子素 + 腦缺血再灌注　； 參考：《河北醫(yī)科大學》2017年碩士論文

【摘要】：腦缺血再灌注后會引起多器官損傷,其機制復雜,氧化應激反應是引發(fā)早期損傷的重要途徑之一。蛇床子素(Osthole,OST)屬于天然香豆素類化合物,前期實驗研究發(fā)現(xiàn),蛇床子素對腦缺血再灌注引起的多器官損傷有保護功效,此結果是否通過氧化應激途徑發(fā)揮作用,是本課題研究的主要內(nèi)容。目的:在全腦缺血再灌注小鼠模型上,觀察蛇床子素對心肺組織氧化應激指標的影響,分析其保護作用機制。方法:采用改進的Himori法暫時性阻斷兩側頸總動脈制備小鼠腦缺血再灌注損傷的模型,50只小鼠,隨機分為5組,分別為假手術組(進行手術,但不進行腦缺血再灌注)、模型組(即腦缺血再灌注組)、蛇床子素高劑量組、中劑量組和低劑量組,高、中、低劑量組于缺血前30min分別腹腔注射(ip)蛇床子素10 mg·kg~(-1),1.0 mg·kg~(-1),0.1mg·kg~(-1);假手術組與模型組分別ip等體積溶劑l0ml·kg~(-1)(按N,N-二甲基甲酰胺:吐溫80:生理鹽水等于1:1:8配制)。應用生化試驗盒檢測小鼠心肺組織及血漿中超氧化物歧化酶(superoxide dismutase,SOD);過氧化氫酶(catalase,CAT);谷胱甘肽過氧化物酶(glutathioneperoxidase,GSH-PX)的活性及丙二醛(malondialdehyde,MDA)的含量,統(tǒng)計分析上述指標變化。結果:1腦缺血再灌注小鼠心肌組織內(nèi)GSH-PX,SOD,CAT活性和MDA含量變化與假手術組比較,模型組小鼠心肌內(nèi)GSH-PX、CAT、SOD活性顯著降低(P0.01),MDA含量顯著增高(P0.01);與模型組比較,蛇床子素組的GSH-PX、SOD活性均顯著提高(高劑量組P0.01,中、低劑量組P0.05),CAT活性明顯提高(高劑量組P0.01,中劑量組P0.05),MDA含量顯著降低(高劑量組P0.01,中、低劑量組P0.05)。2腦缺血再灌注小鼠肺組織內(nèi)GSH-PX,SOD,CAT活性和MDA含量變化與假手術組比較,模型組小鼠的GSH-PX,SOD,CAT活性顯著降低(P0.01),MDA含量顯著增高(P0.01);與模型組比較,蛇床子素組GSH-PX活性明顯提高(高劑量組P0.01,中劑量組P0.05),CAT、SOD活性明顯提高(高劑量組P0.01,中、低劑量組P0.05),MDA含量顯著降低(高劑量組P0.01,中、低劑量組P0.05)。3腦缺血再灌注小鼠血液內(nèi)GSH-PX,SOD,CAT活性和MDA含量變化與假手術組比較,模型組小鼠的GSH-PX,SOD,CAT活性顯著降低(P0.01),MDA含量顯著增高(P0.01);與模型組比較,蛇床子素組GSH-PX、CAT、SOD活性明顯提高(高劑量組P0.01,中劑量組P0.05),MDA含量顯著降低(高劑量組P0.01,中劑量組P0.05)。結論:腦缺血再灌注模型小鼠,其心肌組織、肺和血液中GSH-PX,SOD,CAT的活力明顯下降,MDA的含量顯著增高,出現(xiàn)明顯的氧化應激反應;蛇床子素可顯著改善此種氧化應激反應,提示對腦缺血再灌注后的心肺組織起到保護作用。
[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.
【學位授予單位】：河北醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R285.5

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