知母皂苷对心肌缺血损伤的保护作用及其机制研究

发布时间：2018-06-05 13:31

  本文选题：知母皂苷 + 心肌缺血　； 参考：《西南交通大学》2017年硕士论文

【摘要】：目的:研究灌胃给药的知母皂苷Officinalisinin Ⅰ及知母皂苷bⅡ对心肌缺血的保护作用及知母皂苷Officinalisinin Ⅰ的作用机制。研究腹腔注射给药知知母皂苷Officinalisinin Ⅰ对心肌缺血的保护作用及作用机制。方法:(1)实验大鼠随机分为空白组、模型组、Officinalisinin Ⅰ与知母皂苷bⅡ高低剂量组和阳性组,共7组。用异丙肾上腺素制备急性心肌缺血模型。分别用知母皂苷 Officinalisinin Ⅰ(300、600mg/kg)、知母皂苷 bⅡ(300、600mg/kg)和地奥心血康(阳性对照,120mg/kg)灌胃,5d后,处死动物,取心肌组织做病理切片,观察心肌组织病理学变化;检测大鼠血清中LDH、CK、AST指标变化。(2)实验大鼠随机分为空白组、模型组、知母皂苷Officinalisinin Ⅰ高低剂量组和阳性组,共5组。用异丙肾上腺素制备急性心肌缺血模型。分别用知母皂苷Officinalisinin Ⅰ(300、600mg/kg)和地奥心血康(阳性对照,120mg/kg)灌胃,5d后,取心肌组织匀浆,检测各组心肌组织匀浆中的Gsh-px、SOD、ROS、MDA;Bcl-2、BAX、p53以及HO-1水平变化。(3)实验大鼠随机分为空白组、模型组、知母皂苷Officinalisinin Ⅰ高中低剂量组和阳性组,共6组。用异丙肾上腺素制备急性心肌缺血模型。分别用知母皂苷Officinalisinin Ⅰ(100、50、25mg/kg)和地奥心血康(阳性对照,100mg/kg)腹腔注射,5d后,取心肌组织做病理切片,观察心肌组织病理学变化;检测大鼠血清中LDH、CK、AST指标变化。取心肌组织匀浆,检测各组心肌组织匀浆中的Gsh-px、SOD、ROS、MDA;Bcl-2、BAX、p53以及HO-1水平变化,Tunel法检测细胞凋亡。结果:(1)灌胃给药的知母皂苷Officinalisinin Ⅰ与知母皂苷bⅡ均可以改善心肌缺血模型病理学变化。两者均可以不同程度降低心肌缺血模型血清中LDH、CK、AST的水平,知母皂苷Officinalisinin Ⅰ各组相比知母皂苷bⅡ各组能够更大程度降低心肌缺血模型血清中LDH、CK、AST的水平。(2)灌胃给药的知母皂苷OfficinalisininⅠ可以降低心肌缺血模型心肌组织中MDA、ROS水平,并能提高心肌组织中Gsh-px与SOD活力;可以降低心肌缺血模型心肌组织中Bax、p53的水平,并能提高心肌组织中Bcl-2的水平,提高Bcl-2/Bax的比值;但其对心肌缺血模型心肌组织中HO-1蛋白水平无显著影响(3)腹腔注射给药的知母皂苷OfficinalisininⅠ能够改善心肌缺血模型病理学变化并可以降低心肌缺血模型血清中LDH、CK、AST的水平。同时,还能够降低心肌缺血模型心肌组织中MDA、ROS水平,并能提高心肌组织中Gsh-px与SOD活力;可以抑制细胞凋亡,并降低心肌缺血模型心肌组织中Bax、p53的水平,提高心肌组织中Bcl-2的水平,提高Bcl-2/Bax的比值。腹腔注射给药知母皂苷OfficinalisininⅠ相比灌胃给药知母皂苷OfficinalisininⅠ对大鼠急性心肌缺血模型治疗的有效剂量显著降低。结论:(1)知母皂苷OfficinalisininⅠ与知母皂苷bⅡ两者均具有保护急性心肌缺血损伤的作用,且知母皂苷OfficinalisininⅠ对急性心肌缺血损伤的保护作用比知母皂苷bⅡ更显著。(2)灌胃给药知母皂苷OfficinalisininⅠ可以降低心肌缺血模型心肌组织中MDA、ROS水平,并提高心肌组织中Gsh-px与SOD活力,提示其通过抗自由基及过氧化,保护心肌组织;知母皂苷OfficinalisininⅠ可以提高Bcl-2/Bax的比值,降低p53水平,对HO-1蛋白无明显作用。说明其减少心肌细胞凋亡的作用机制与改善心肌细胞凋亡蛋白有关,而HO-1蛋白无关。(3)腹腔注射给药知母皂苷OfficinalisininⅠ,对急性心肌缺血损伤同样具有保护作用。其作用机制与抗自由基及过氧化、抑制细胞凋亡,改善心肌细胞凋亡蛋白表达有关。使用腹腔注射给药方法给药,相比使用灌胃给药方法给药,药物的有效剂量明显降低。推测是由于腹腔注射给药的方式比起灌胃给药的方式,吸收更快更完全,生物利用度更高。
[Abstract]:Objective: To study the protective effect of the saponins Officinalisinin I and the saponins B II of the Anemarrhena saponins on the myocardial ischemia and the mechanism of the action of the saponin Officinalisinin I of Anemarrhena Anemarrhena II. The protective effect and mechanism of saponin Officinalisinin I on the myocardial ischemia were studied by intraperitoneal injection. Methods: (1) the experimental rats were randomly divided into empty space. The white group, the model group, the Officinalisinin I and the Anemarrhena saponins B II high and low dose group and the positive group were 7 groups. The acute myocardial ischemia models were prepared with isoproterenol, using the saponins Officinalisinin I (300600mg/kg), the saponins B II (300600mg/kg) of the Anemarrhena Anemarrhena (300600mg/kg) and the Diao Xin Xue Kang (positive control, 120mg/kg). After 5D, the animals were killed. The pathological changes of myocardial tissue were taken to observe the changes of myocardial histopathology, and the changes of LDH, CK and AST in the serum of rats were detected. (2) the experimental rats were randomly divided into blank group, model group, high and low dose group of saponin Officinalisinin I of Anemarrhena anemonaris and positive group, and the acute myocardial ischemia model was prepared by ISO propionic adenine, respectively, using the saponins Off of Anemarrhena Anemarrhena, respectively. Icinalisinin I (300600mg/kg) and Diao Xin Xue Kang (positive control, 120mg/kg) were gavage. After 5D, the myocardial homogenate was taken and the Gsh-px, SOD, ROS, MDA, Bcl-2, BAX, p53, and HO-1 levels were detected in the homogenate of each group. (3) the experimental rats were randomly divided into blank group, model group, and Anemarrhena saponin I high school low dose group and Yang Acute myocardial ischemia models were made with isoproterenol (100,50,25mg/kg) and Diao Xin Xue Kang (positive control, 100mg/kg) in 6 groups. After 5D, the myocardial tissue was taken for pathological section to observe the pathological changes of myocardium, and the changes of LDH, CK and AST in serum were detected. Muscle tissue homogenate was used to detect Gsh-px, SOD, ROS, MDA, Bcl-2, BAX, p53, and HO-1 levels in all groups of myocardial tissue, and the apoptosis was detected by Tunel method. Results: (1) the pathological changes in the myocardial ischemia model could be improved by both the saponins Officinalisinin I and the saponins of the Anemarrhena Anemarrhena. Both of them could reduce the myocardium in different degrees. The level of LDH, CK, AST in the serum of ischemic model, each group of saponins Officinalisinin I of Anemarrhena saponins Officinalisinin I can lower the level of LDH, CK, AST in the serum of myocardial ischemia model to a greater degree. (2) the mother saponins Officinalisinin I administered by gavage can reduce the MDA, ROS level in myocardial ischemia model and can improve the heart The activity of Gsh-px and SOD in muscle tissue can reduce the level of Bax and p53 in myocardial ischemia model and improve the level of Bcl-2 in myocardial tissue and increase the ratio of Bcl-2/Bax, but it has no significant effect on the level of HO-1 protein in myocardial ischemia model (3) the ameliorate of the saponins Officinalisinin I with the injection of abdominal cavity injection can be improved. The pathological changes of myocardial ischemia model can reduce the level of LDH, CK and AST in the serum of myocardial ischemia model. At the same time, it can also reduce the level of MDA and ROS in myocardial ischemia model and improve the activity of Gsh-px and SOD in myocardial tissue, inhibit apoptosis and reduce the level of Bax and p53 in myocardial tissue of myocardial ischemia model, and raise the level of Bax and p53 in myocardial ischemia model. The level of Bcl-2 in high myocardial tissue and the ratio of Bcl-2/Bax. Intraperitoneal injection of Anemarrhena saponins Officinalisinin I significantly decreased the effective dose of saponin Officinalisinin I on acute myocardial ischemia model in rats. Conclusion: (1) both the saponins Officinalisinin I and the saponins B II of Anemarrhena Anemarrhena were both guaranteed. Protecting the acute myocardial ischemia injury, and the protective effect of saponins Officinalisinin I on acute myocardial ischemia is more significant than that of the saponins B II. (2) gavage to the Anemarrhena saponins Officinalisinin I can reduce the level of MDA and ROS in myocardial ischemia model and improve the activity of Gsh-px and SOD in myocardial tissue. The protection of myocardial tissue by anti free radicals and peroxidation; the saponin Officinalisinin I of Anemarrhena saponins I can improve the ratio of Bcl-2/Bax, reduce the level of p53, and have no obvious effect on HO-1 protein. It shows that the mechanism of its reduction of cardiomyocyte apoptosis is related to the improvement of cardiomyocyte apoptosis protein, but the HO-1 protein has nothing to do. (3) intraperitoneal injection of Anemarrhena saponins Of Ficinalisinin I also has a protective effect on acute myocardial ischemia. Its mechanism is related to the anti free radical and peroxidation, inhibition of apoptosis and the improvement of the expression of apoptotic protein in cardiac myocytes. The effective dose of the drug is obviously reduced compared with the method of intraperitoneal injection. The method of intraperitoneal injection is faster and more complete and has higher bioavailability than the way of gavage.
【学位授予单位】：西南交通大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R285.5

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