本文選題：知母皂苷 + 心肌缺血��； 參考：《西南交通大學(xué)》2017年碩士論文

【摘要】：目的:研究灌胃給藥的知母皂苷Officinalisinin Ⅰ及知母皂苷bⅡ?qū)π募∪毖谋Ｗo(hù)作用及知母皂苷Officinalisinin Ⅰ的作用機(jī)制。研究腹腔注射給藥知知母皂苷Officinalisinin Ⅰ對(duì)心肌缺血的保護(hù)作用及作用機(jī)制。方法:(1)實(shí)驗(yàn)大鼠隨機(jī)分為空白組、模型組、Officinalisinin Ⅰ與知母皂苷bⅡ高低劑量組和陽性組,共7組。用異丙腎上腺素制備急性心肌缺血模型。分別用知母皂苷 Officinalisinin Ⅰ(300、600mg/kg)、知母皂苷 bⅡ(300、600mg/kg)和地奧心血康(陽性對(duì)照,120mg/kg)灌胃,5d后,處死動(dòng)物,取心肌組織做病理切片,觀察心肌組織病理學(xué)變化;檢測大鼠血清中LDH、CK、AST指標(biāo)變化。(2)實(shí)驗(yàn)大鼠隨機(jī)分為空白組、模型組、知母皂苷Officinalisinin Ⅰ高低劑量組和陽性組,共5組。用異丙腎上腺素制備急性心肌缺血模型。分別用知母皂苷Officinalisinin Ⅰ(300、600mg/kg)和地奧心血康(陽性對(duì)照,120mg/kg)灌胃,5d后,取心肌組織勻漿,檢測各組心肌組織勻漿中的Gsh-px、SOD、ROS、MDA;Bcl-2、BAX、p53以及HO-1水平變化。(3)實(shí)驗(yàn)大鼠隨機(jī)分為空白組、模型組、知母皂苷Officinalisinin Ⅰ高中低劑量組和陽性組,共6組。用異丙腎上腺素制備急性心肌缺血模型。分別用知母皂苷Officinalisinin Ⅰ(100、50、25mg/kg)和地奧心血康(陽性對(duì)照,100mg/kg)腹腔注射,5d后,取心肌組織做病理切片,觀察心肌組織病理學(xué)變化;檢測大鼠血清中LDH、CK、AST指標(biāo)變化。取心肌組織勻漿,檢測各組心肌組織勻漿中的Gsh-px、SOD、ROS、MDA;Bcl-2、BAX、p53以及HO-1水平變化,Tunel法檢測細(xì)胞凋亡。結(jié)果:(1)灌胃給藥的知母皂苷Officinalisinin Ⅰ與知母皂苷bⅡ均可以改善心肌缺血模型病理學(xué)變化。兩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各組相比知母皂苷bⅡ各組能夠更大程度降低心肌缺血模型血清中LDH、CK、AST的水平。(2)灌胃給藥的知母皂苷OfficinalisininⅠ可以降低心肌缺血模型心肌組織中MDA、ROS水平,并能提高心肌組織中Gsh-px與SOD活力;可以降低心肌缺血模型心肌組織中Bax、p53的水平,并能提高心肌組織中Bcl-2的水平,提高Bcl-2/Bax的比值;但其對(duì)心肌缺血模型心肌組織中HO-1蛋白水平無顯著影響(3)腹腔注射給藥的知母皂苷OfficinalisininⅠ能夠改善心肌缺血模型病理學(xué)變化并可以降低心肌缺血模型血清中LDH、CK、AST的水平。同時(shí),還能夠降低心肌缺血模型心肌組織中MDA、ROS水平,并能提高心肌組織中Gsh-px與SOD活力;可以抑制細(xì)胞凋亡,并降低心肌缺血模型心肌組織中Bax、p53的水平,提高心肌組織中Bcl-2的水平,提高Bcl-2/Bax的比值。腹腔注射給藥知母皂苷OfficinalisininⅠ相比灌胃給藥知母皂苷OfficinalisininⅠ對(duì)大鼠急性心肌缺血模型治療的有效劑量顯著降低。結(jié)論:(1)知母皂苷OfficinalisininⅠ與知母皂苷bⅡ兩者均具有保護(hù)急性心肌缺血損傷的作用,且知母皂苷OfficinalisininⅠ對(duì)急性心肌缺血損傷的保護(hù)作用比知母皂苷bⅡ更顯著。(2)灌胃給藥知母皂苷OfficinalisininⅠ可以降低心肌缺血模型心肌組織中MDA、ROS水平,并提高心肌組織中Gsh-px與SOD活力,提示其通過抗自由基及過氧化,保護(hù)心肌組織;知母皂苷OfficinalisininⅠ可以提高Bcl-2/Bax的比值,降低p53水平,對(duì)HO-1蛋白無明顯作用。說明其減少心肌細(xì)胞凋亡的作用機(jī)制與改善心肌細(xì)胞凋亡蛋白有關(guān),而HO-1蛋白無關(guān)。(3)腹腔注射給藥知母皂苷OfficinalisininⅠ,對(duì)急性心肌缺血損傷同樣具有保護(hù)作用。其作用機(jī)制與抗自由基及過氧化、抑制細(xì)胞凋亡,改善心肌細(xì)胞凋亡蛋白表達(dá)有關(guān)。使用腹腔注射給藥方法給藥,相比使用灌胃給藥方法給藥,藥物的有效劑量明顯降低。推測是由于腹腔注射給藥的方式比起灌胃給藥的方式,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.
【學(xué)位授予單位】：西南交通大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R285.5

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