细胞外HSP70对小鼠心肌缺血再灌注损伤作用的实验研究

发布时间：2018-04-01 02:02

本文选题：热休克蛋白　切入点：缺血再灌注损伤　出处：《华中科技大学》2007年硕士论文

【摘要】： 细胞内HSP70对心肌的保护作用已经得到证实,但近年来有研究表明细胞外HSP70有促进炎症因子表达、释放的作用,且在心肌损伤时(如心肌梗死、冠状动脉旁路移植术后)细胞外HSP70水平有显著性升高,而炎性反应在心肌缺血再灌注损伤中起着重要作用。细胞外HSP70在心肌缺血再灌注损伤中的变化及作用少见研究报道。本研究采用在体小鼠心肌缺血再灌注模型,观察心肌缺血再灌注中细胞外HSP70的变化情况,并研究其在心肌缺血再灌注损伤中的作用及可能机制。第一部分细胞外HSP70与心肌缺血再灌注损伤的相关性研究目的:研究急性心肌缺血再灌注损伤过程中细胞外HSP70的变化,及此变化与心肌缺血再灌注损伤程度的相关性。方法:20只雄性昆明小鼠随机分成二组,即假手术组、缺血再灌注组,检测两组术前及术后1h、3h、5h血清中的HSP70的浓度及缺血再灌注组再灌注1h、3h、5h时血清中CK活性。结果:缺血再灌注组再灌注1h、3h、5h血清中HSP70水平较假手术组有显著性的升高(p0.05),并于再灌注3h时达高峰,且再灌注后血清中HSP70的浓度与CK的水平呈正相关(r=0.879,p0.001)。结论:缺血再灌注过程会引起细胞外HSP70浓度升高,且此升高程度与心肌缺血再灌注损伤程度呈正相关。第二部分细胞外HSP70在小鼠心肌缺血再灌注损伤中的作用目的:研究细胞外HSP70在小鼠心肌缺血再灌注损伤中的作用及其可能机制。方法:将雄性昆明小鼠随机分成三组,即假手术组(A组)、缺血再灌注组(B组)及HSP70处理组(C组),后两组建立小鼠心肌缺血再灌注动物模型,再灌注时经颈总动脉插管分别注射0.2ml灭菌生理盐水或0.2mlHSP70。检测各组再灌注5h时血清中CK及乳酸脱氢酶(LDH)的活性,和心肌组织中髓过氧化物酶(MPO)活性、丙二醛(MDA)含量及NF-κB表达。结果:B组CK、LDH、MPO活性、MDA含量和NF-κB表达均比A组明显升高(p0.01),而C组CK、LDH、MPO活性、MDA含量和NF-κB表达比B组明显升高(p0.05); 结论:同源性细胞外HSP70有加重心肌再灌注损伤的作用,其机制可能是通过膜受体(TLR-4)激活NF-κB,促发炎症反应,致多型核中性粒细胞浸润(PMNs)和活性氧的生成增加,从而加重心肌再灌注的炎症反应。
[Abstract]:The protective effect of intracellular HSP70 on myocardium has been confirmed, but in recent years, studies have shown that extracellular HSP70 can promote the expression and release of inflammatory factors, and in myocardial injury (such as myocardial infarction, for example, myocardial infarction), The level of extracellular HSP70 increased significantly after coronary artery bypass grafting. However, inflammatory response plays an important role in myocardial ischemia-reperfusion injury. The changes and effects of extracellular HSP70 in myocardial ischemia-reperfusion injury are rarely reported. To observe the changes of extracellular HSP70 during myocardial ischemia-reperfusion, and to study the role and possible mechanism of extracellular HSP70 in myocardial ischemia-reperfusion injury. The relationship between extracellular HSP70 and myocardial ischemia-reperfusion injury. Aim: to study the changes of extracellular HSP70 during acute myocardial ischemia-reperfusion injury and the relationship between the changes and the degree of myocardial ischemia-reperfusion injury. Methods Twenty male Kunming mice were randomly divided into two groups: sham-operated group and ischemia-reperfusion group. The serum HSP70 concentration before and 1 hour after operation and the serum CK activity in the ischemia reperfusion group were measured. Results: the serum HSP70 level in the ischemia reperfusion group was significantly higher than that in the sham operation group at 1 h, 3 h and 5 h after reperfusion, and reached its peak at 3 h after reperfusion. The serum HSP70 concentration was positively correlated with the level of CK. Conclusion: the concentration of extracellular HSP70 is increased during ischemia reperfusion, and the degree of increase is positively correlated with the degree of myocardial ischemia reperfusion injury. The role of extracellular HSP70 in myocardial ischemia-reperfusion injury in mice. Aim: to study the effect of extracellular HSP70 on myocardial ischemia reperfusion injury in mice and its possible mechanism. Methods: male Kunming mice were randomly divided into three groups: sham operation group (group A), ischemia-reperfusion group (group B) and HSP70 treatment group (group C). During reperfusion, 0.2ml sterilized saline or 0.2 ml HSP70 were injected into the common carotid artery respectively. The activities of CK and lactate dehydrogenase (LDH) in serum, myeloperoxidase (MPO) activity, malondialdehyde (MDA) content and NF- 魏 B expression in myocardium were measured at 5 h after reperfusion. Results the content of MDA and the expression of NF- 魏 B in group C were significantly higher than those in group A, while the content of MDA and the expression of NF- 魏 B in group C were significantly higher than those in group B. Conclusion: extracellular homologous HSP70 can aggravate myocardial reperfusion injury, and its mechanism may be that NF- 魏 B is activated by membrane receptor TLR-4, inflammation is induced, PMNs are infiltrated by polymorphonuclear neutrophils (PMNs) and reactive oxygen species (Ros) production is increased. Thus exacerbating the inflammatory response of myocardial reperfusion.
【学位授予单位】：华中科技大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R363

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