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舒芬太尼后处理对非糖尿病和糖尿病大鼠心肌缺血再灌注损伤的影响及其与PI3K-Akt通路、Cyt-C的关系

发布时间:2018-07-27 19:20
【摘要】:目的:研究舒芬太尼后处理对非糖尿病(non-diabetic mellitus,NDM)和糖尿病大鼠(diabetic mellitus,DM)心肌缺血再灌注损伤(Myocardial ischemia/reperfusion injury,MI/RI)的影响及其与磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)-蛋白激酶B(Akt)通路、细胞色素C(Cytochrome C,Cyt-C)的关系。方法:选择健康SD大鼠二十四只,利用随机数字表法,将其分为四组(n=6):分别是NDM假手术组(NDM-S组)、缺血再灌注组(NDM-I/R组)、舒芬太尼后处理组(NDM-SP组)、舒芬太尼后处理+渥曼青霉素(PI3K抑制剂)组(NDM-SP+W组)。另外重新选择健康SD大鼠,将其制备成DM大鼠,选取造模成功的大鼠二十四只,将其也分为四组(n=6):DM假手术组(DM-S组)、缺血再灌注组(DM-I/R组)、舒芬太尼后处理组(DM-SP组)、舒芬太尼后处理+渥曼青霉素组(DM-SP+W组)。结扎其LAD制备大鼠MI/RI的模型。其中S组只穿线不结扎;I/R组穿线后稳定5min,阻断30min,再灌注120min;SP组于恢复灌注前5min静注舒芬太尼1.0μg/kg;SP+W组于恢复灌注前5min静注渥曼青霉素15μg/kg和舒芬太尼1.0μg/kg。实验完毕后取血,测肌钙蛋白I(c Tn I)的浓度;处死大鼠并收集心肌组织,采用TUNEL法测定心肌细胞的凋亡指数(AI);Western blot法检测心肌组织Akt、p-Akt、Cyt-C的表达水平。结果:舒芬太尼后处理可明显减轻NDM组的MI/RI,使升高的c Tn I浓度降低、AI降低,p-Akt的表达增加、Cyt-C的表达下调,而对DM组MI/RI的各项指标均无明显的影响。NDM-SP组的血浆c Tn I的浓度、AI、Cyt-C的表达明显低于DM-SP组而p-Akt的表达高于DM-SP组。结论:舒芬太尼后处理对NDM大鼠MI/RI有保护作用,通过PI3K-Akt通路减少了Cyt-C的释放。而对DM大鼠MI/RI没有保护作用,PI3K-Akt通路不参与该过程。
[Abstract]:Aim: to study the effects of sufentanil postconditioning on myocardial ischemia-reperfusion injury (Myocardial ischemia/reperfusion / RI) in non-diabetic Mellitus diabetic rats and its relationship with phosphatidylinositol 3-kinase- PI3K-protein kinase B (Akt) pathway, cytochrome C (Cytochrome Cyt-C. Methods: 24 healthy Sprague-Dawley rats were selected. They were divided into four groups: NDM sham-operation group (NDM-S group), ischemia-reperfusion group (NDM-I/R group), sufentanil post-treatment group (NDM-SP group) and sufentanil post-treated womanpenicillin (NDM-SP W group). In addition, healthy SD rats were re-selected and made into DM rats. 24 rats were selected for successful modeling. They were also divided into four groups: sham operation group (DM-S group), ischemia reperfusion group (DM-I/R group), sufentanil aftertreatment group (DM-SP group), and sufentanil aftertreatment group (DM-SP W group). The rat model of MI/RI was established by ligating its LAD. In S group, sufentanil 1.0 渭 g / kg SP W was injected intravenously with womanpenicillin 15 渭 g/kg and sufentanil 1.0 渭 g / kg 路kg before reperfusion in group S, only 5 minutes after ligation without ligation, and 30 minutes after occlusion, and 120 minutes after reperfusion. The patients in group S received intravenous injection of sufentanil (1.0 渭 g / kg) and sufentanil (15 渭 g / kg) before reperfusion. At the end of the experiment, the concentration of troponin I (c Tn I) was measured, and the myocardial tissue was collected and killed. The apoptosis index (AI) of myocardial cells was measured by TUNEL, and the expression of Akttip-Akttiocyt C in myocardial tissue was detected by (AI) blot. Results: after treatment with sufentanil, MI-RI in NDM group was significantly alleviated, and the increased c Tn I concentration decreased the expression of p-Akt, increased the down-regulation of Cyt-C expression. However, there was no significant effect on the indexes of MI/RI in DM group. The level of plasma c Tn I in NDM-SP group was significantly lower than that in DM-SP group, and the expression of p-Akt was higher than that in DM-SP group. Conclusion: sufentanil post-treatment has protective effect on MI/RI in NDM rats and reduces the release of Cyt-C through PI3K-Akt pathway. The PI3 K-Akt pathway was not involved in the process of MI/RI in DM rats.
【学位授予单位】:山西医科大学
【学位级别】:硕士
【学位授予年份】:2015
【分类号】:R614

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