【作者】 杨琳；

【导师】 周玉娟；

【作者基本信息】 河北大学 ， 药理学， 2014， 硕士

【摘要】 目的：观察丹七对兔心肌缺血再灌注损伤的保护作用，探讨其可能的作用机制。方法：18只健康清洁级新西兰大耳白，随机分为3组：假手术组、模型组、丹七干预组。每组正常喂食，丹七干预组每天给予丹七片400mg·kg-1·d-1灌胃，假手术组和模型组每天给予等量蒸馏水灌胃，连续应用一周。末次给药1h后，采用结扎兔左冠状动脉前降支的方法制备缺血再灌注损伤模型。运用BL-420F生物机能实验系统记录各组动物左心功能指标的变化。再灌注120min后颈总动脉取血，离心血清，比色法检测磷酸肌酸激酶(CK)、乳酸脱氢酶(LDH)、一氧化氮合酶(NOS)、超氧化物歧化酶(SOD)、一氧化氮(NO)、丙二醛(MDA)。酶联免疫吸附法测量白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、可溶性细胞间粘附分子-1(sICAM-1)。取心肌组织， HE染色光镜观察病理改变。结果：1、模型组与假手术组相比出现明显的心肌缺血再灌注损伤的病理表现，丹七干预组心肌缺血再灌注损伤的病理改变比模型组有所减轻。2、模型组左心功能指标左心室收缩压(LVSP)、左心室内压最大上升速率(+dp/dtmax)、左心室内压最大下降速率(-dp/dtmax)的数值比假手术组明显降低，左心室舒张末压(LVEDP)的数值比假手术组明显升高（P＜0.05）。丹七干预组LVSP、+dp/dtmax、-dp/dtmax数值比模型组有所上升，LVEDP数值比模型组有所下降（P＜0.05）。3、模型组CK、LDH的水平高于假手术组（P＜0.05）。丹七干预组CK、LDH的水平比模型组有所降低（P＜0.05）。4、模型组SOD、NOS、NO水平低于假手术组，MDA水平高于假手术组（P＜0.05）。丹七干预组SOD、NOS、NO水平高于模型组，MDA水平低于模型组（P＜0.05）。5、模型组IL-6、TNF-α、sICAM-1的含量高于假手术组（P＜0.05）。丹七干预组IL-6、TNF-α、sICAM-1的含量低于模型组（P＜0.05）。结论：1、丹七可以改善兔MIRI模型中心肌组织的病理变化。2、丹七可以改善兔MIRI模型中的心功能，降低血清中CK、LDH的水平，减轻心肌的损伤。3、丹七通过升高血清SOD、NOS、NO水平，降低MDA水平，减轻MIRI中的氧化应激，从而抑制MIRI的发生发展。4、丹七通过减少IL-6、TNF-α、sICAM-1的含量，从一定程度上抑制MIRI的炎症反应，从而保护缺血再灌注损伤的心肌。更多还原

【Abstract】 Objective:To observe the protective effect of Danqi on myocardial ischemia reperfusion injury inrabbits, and to explore its possible mechanism.Methods:Eighteen healthy rabbits were randomly divided into three guoups: sham operation,model group, Danqi intervention group. Each group of normal feeding, Danqi interventiongroup were given Danqi400mg·kg-1·d-1every day, sham operation and model group weregiven distilled water by gavage every day, continuous application of a week. One hour afterthe last administration, the ligation of the left anterior descending coronary artery method toprepare the model of ischemia reperfusion injury. Using the BL-420F biological andfunctional experimental system recorded the changes of left ventricular function indexes;After reperfusion120minutes, collecting blood sample from common carotid artery,centrifugal serum. Than to detect kinase colorimetric method(CK), lactatedehydrogenase(LDH), nitric oxide synthase(NOS), superoxide dismutase(SOD), nitricoxide(NO), malondialdehyde(MDA). Enzyme linked immunosorbent assay measuringinterleukin-6(IL-6), tumor necrosis factor alpha(TNF-α), soluble intercellular adhesionmolecule-1(sICAM-1). HE staining to observe the myocardial tissue pathological changes.Results:1The model group appeared obvious pathological manifestations of myocardialischemia reperfusion injury compared with the sham operation group, the Danqi interventiongroup pathological changes of myocardial ischemia reperfusion injury reduced than themodel group.2In model group, the left ventricular function indexes of left ventricular systolicpressure (LVSP), the maximum rise rate of left ventricular pressure(+dp/dtmax), the maximumfall rate of left ventricular pressure (-dp/dtmax) value was lower than that of sham operationgroup, the left ventricular end-diastolic pressure (LVEDP) value was higher than the shamoperation group (P<0.05). In Danqi intervention group, LVSP,+dp/dtmax,-dp/dtmaxvaluehigher than the model group, the LVEDP value lower than the model group (P<0.05). 3In model group, the level of CK and LDH were higher than the sham operationgroup (P<0.05). The level of CK and LDH in Danqi intervention group were lower thanmodel group (P<0.05).4The model group SOD, NOS, NO levels are lower than those in the sham operationgroup, the MDA level is higher than the sham operation group (P<0.05). The Danqiintervention groups SOD, NOS, NO levels are higher than the model group, the MDA level islower than the model group (P<0.05).5In the model group IL-6, TNF-α, sICAM-1are higher than those in the shamoperation group (P<0.05). The Danqi intervention group IL-6, TNF-α, sICAM-1are lowerthan that of model group (P <0.05).Conclusion:1Danqi can improve the pathological changes of myocardial tissue of rabbits in MIRImodel.2Danqi can improve cardiac function of rabbits in the model of MIRI, decrease thelevel of CK, LDH in serum.3Danqi can increase the level of SOD, NOS, NO in serum, decrease the level of MDA,decrease oxidative stress in MIRI development, so as to suppress MIRI.4Danqi through reducing IL-6, TNF-α, sICAM-1content, inhibit the inflammatoryreaction of MIRI from a certain extent, so as to protect the ischemia reperfusion injury ofmyocardium.更多还原