舒芬太尼预处理对缺血再灌注损伤心肌细胞自噬的影响

发布时间：2018-05-10 09:15

本文选题：心肌缺血再灌注损伤 + 自噬　；参考：《广州中医药大学》2015年硕士论文

【摘要】：背景：急性心肌梗死(Acute Myocardial Infarction, AMI)是指冠状动脉急性闭塞,血流中断,所引起的局部心肌的缺血性坏死,是冠心病的主要死因。在冠状动脉闭塞的早期,通过干预恢复血流供应可以减轻对心肌细胞的损伤。然而,恢复冠脉血流供应时会导致不可逆的心肌损伤,这种现象被称为心肌缺血再灌注损伤(Myocardial Ischemia Reperfusion Injury, MIRI)。 MIRI机制及心肌保护的研究一直是当今倍受重视的课题。1986年,Murry等人提出缺血预处理的(ischemic preconditioning, IPC)概念,大量实验研究证实了缺血预处理是最行之有效的心脏保护措施。但是由于缺血预处理的实施方法的特定条件,难以在临床上付诸实践,近20年,人们又提出药物预处理(pharmacological preconditioning),对于心肌缺血再灌注也有类似IPC的保护效应,其中包括麻醉药物预处理(Anesthetic-induced Preconditioning, APC)。大量研究表明包括腺苷、阿片类镇痛药都对心脏缺血再灌注损伤具有心脏保护作用。随后有更多的研究证实,阿片类物质在整体动物、离体器官、培养的细胞模型,以及人的心脏组织中能够模拟IPC,缓解心肌梗死造成的疼痛,缩小心肌梗死范围,减少心律失常的发生,对心脏具有潜在的保护作用。因此,开发远端缺血预处理(Remote Ischemic Preconditioning, RIPC)及PPC引起了医学界的关注。目的：明确舒芬太尼的抗MIRI作用,观察心肌缺血再灌注损伤过程中心肌细胞自噬水平的改变,初步探讨自噬途径在舒芬太尼心肌保护效应中的作用方法：24只健康雄性SD大鼠(200-250g)随机分为4组,假手术(Sham)组,假手术组+舒芬太尼组(Sham+SF组),缺血再灌注(I/R)组,缺血再灌注+舒芬太尼组(I/R+SF组)。Sham组：只开胸但不结扎冠状动脉,静脉注射等量生理盐水；Sham+SF组：不结扎冠状动脉,相同方式注射舒芬太尼3 μg/kg;I/R组：开胸造MIRI模型(缺血30min,再灌注120min)注射等量生理盐水；I/R+SF组：缺血前泵注舒芬太尼1 μg/kg,泵注5 min,停止5 min,重复3次,总量共3 μg/kg的预处理方式；再灌注120min后于腹主动脉抽取血液2m1,然后取心肌标本。血液标本检测CK-MB、LDH心肌酶；透射电镜测定心肌细胞变化；Western Blot法检测LC3-II/LC3-I、Beclin 1和Bcl-2蛋白表达。结果：与I/R组比较,I/R+SF组心肌酶(CK-MB值)从2538.9 U/L下降到1577.6U/L,差异有统计学意义(P0.05)；与Sham组相比,IR组LC-II蛋白表达明显增高,Bcl-2蛋白表达明显降低,差异有统计学意义(P0.05)；与Sham+SF组相比,I/R+SF组LC-II蛋白表达明显增高,差异有统计学意义(P0.05)；与IR组相比,I/R+SF组Bcl-2蛋白表达增加明显,差异有统计学差异(P0.05)。结论：舒芬太尼在心肌缺血再灌注损伤中具有心肌保护作用。自噬途径可能参与舒芬太尼心肌保护效应的作用机制。
[Abstract]:Background: acute Myocardial Infarction (AMI) is the main cause of death of coronary heart disease (CHD) due to acute coronary artery occlusion (CAO), interruption of blood flow and local myocardial ischemic necrosis. At the early stage of coronary artery occlusion, myocardial injury can be alleviated by intervention to restore blood flow. However, the restoration of coronary blood flow leads to irreversible myocardial injury, which is called myocardial Ischemia Reperfusion injury. The research on the mechanism of MIRI and myocardial protection has been paid more attention to. In 1986, the concept of ischemic preconditioning (IPCs) was put forward by Murry et al. A large number of experimental studies have proved that ischemic preconditioning is the most effective cardiac protection measure. However, due to the specific conditions of the implementation of ischemic preconditioning, it is difficult to put it into practice in clinical practice. In the last 20 years, it has been proposed that drug preconditioning has similar protective effect to myocardial ischemia-reperfusion, which is similar to that of IPC. These include anesthetic-induced preconditioning, APCA. A large number of studies have shown that adenosine and opioid analgesics have cardioprotective effects on myocardial ischemia-reperfusion injury. More studies later confirmed that opiates can mimic IPCs in whole animals, in vitro organs, in cultured models of cells, and in human heart tissue, to relieve the pain caused by myocardial infarction and to reduce the size of myocardial infarction. Reducing the incidence of arrhythmias has a potential protective effect on the heart. Therefore, the development of remote Ischemic conditioning (RIPC) and PPC has attracted the medical attention. Aim: to investigate the effect of sufentanil on MIRI and to observe the changes of myocardial autophagy during myocardial ischemia-reperfusion injury. To explore the role of autophagy pathway in myocardial protection of sufentanil methods Twenty four healthy male Sprague-Dawley rats were randomly divided into four groups: sham group, sham SF group, I / R group. Ischemia reperfusion sufentanil group I / R SF group, I / R SF group, I / R SF group, I / R SF group: open chest but not ligation of coronary artery, intravenous injection of normal saline and Sham SF group: no ligation of coronary artery, In the same way, sufentanil (3 渭 g / kg / R) was injected into MIRI model (30 minutes after ischemia, 120 minutes after reperfusion). The group of I / R was injected with sufentanil 1 渭 g / kg before ischemia for 5 minutes, stopped for 5 minutes, repeated 3 times, and the total amount of 3 渭 g/kg was 3 渭 g/kg. After reperfusion 120min, the blood was drawn from the abdominal aorta for 2 m 1, and then the myocardial specimens were taken. The myocardial enzymes of CK-MBN LDH were detected in blood samples, and the changes of myocardial cells were detected by transmission electron microscope. The expression of LC3-IILC3-IkeBeclin 1 and Bcl-2 protein was detected by Western Blot method. Results: compared with the I / R group, the myocardial enzyme CK-MB value in the I / R SF group decreased from 2538.9 U / L to 1577.6 U / L, the difference was statistically significant (P 0.05), and the expression of LC-II protein in the IR group was significantly higher than that in the Sham group, and the expression of Bcl-2 protein was significantly decreased in the IR group. Compared with the Sham SF group, the expression of LC-II protein in the I- / R SF group was significantly higher than that in the Sham SF group (P 0.05), and the Bcl-2 protein expression in the I / R SF group was significantly higher than that in the IR group (P 0.05). Conclusion: sufentanil has protective effect on myocardial ischemia reperfusion injury. Autophagy pathway may be involved in the mechanism of myocardial protective effect of sufentanil.
【学位授予单位】：广州中医药大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R614

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