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舒芬太尼后處理對非糖尿病和糖尿病大鼠心肌缺血再灌注損傷的影響及其與PI3K-Akt通路、Cyt-C的關(guān)系

發(fā)布時間:2018-07-27 19:20
【摘要】:目的:研究舒芬太尼后處理對非糖尿病(non-diabetic mellitus,NDM)和糖尿病大鼠(diabetic mellitus,DM)心肌缺血再灌注損傷(Myocardial ischemia/reperfusion injury,MI/RI)的影響及其與磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)-蛋白激酶B(Akt)通路、細(xì)胞色素C(Cytochrome C,Cyt-C)的關(guān)系。方法:選擇健康SD大鼠二十四只,利用隨機(jī)數(shù)字表法,將其分為四組(n=6):分別是NDM假手術(shù)組(NDM-S組)、缺血再灌注組(NDM-I/R組)、舒芬太尼后處理組(NDM-SP組)、舒芬太尼后處理+渥曼青霉素(PI3K抑制劑)組(NDM-SP+W組)。另外重新選擇健康SD大鼠,將其制備成DM大鼠,選取造模成功的大鼠二十四只,將其也分為四組(n=6):DM假手術(shù)組(DM-S組)、缺血再灌注組(DM-I/R組)、舒芬太尼后處理組(DM-SP組)、舒芬太尼后處理+渥曼青霉素組(DM-SP+W組)。結(jié)扎其LAD制備大鼠MI/RI的模型。其中S組只穿線不結(jié)扎;I/R組穿線后穩(wěn)定5min,阻斷30min,再灌注120min;SP組于恢復(fù)灌注前5min靜注舒芬太尼1.0μg/kg;SP+W組于恢復(fù)灌注前5min靜注渥曼青霉素15μg/kg和舒芬太尼1.0μg/kg。實驗完畢后取血,測肌鈣蛋白I(c Tn I)的濃度;處死大鼠并收集心肌組織,采用TUNEL法測定心肌細(xì)胞的凋亡指數(shù)(AI);Western blot法檢測心肌組織Akt、p-Akt、Cyt-C的表達(dá)水平。結(jié)果:舒芬太尼后處理可明顯減輕NDM組的MI/RI,使升高的c Tn I濃度降低、AI降低,p-Akt的表達(dá)增加、Cyt-C的表達(dá)下調(diào),而對DM組MI/RI的各項指標(biāo)均無明顯的影響。NDM-SP組的血漿c Tn I的濃度、AI、Cyt-C的表達(dá)明顯低于DM-SP組而p-Akt的表達(dá)高于DM-SP組。結(jié)論:舒芬太尼后處理對NDM大鼠MI/RI有保護(hù)作用,通過PI3K-Akt通路減少了Cyt-C的釋放。而對DM大鼠MI/RI沒有保護(hù)作用,PI3K-Akt通路不參與該過程。
[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.
【學(xué)位授予單位】:山西醫(yī)科大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2015
【分類號】:R614

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