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

发布时间：2018-09-12 16:32

【摘要】：目的:探讨在糖尿病和非糖尿病大鼠心肌缺血再灌注损伤(myocardial ischemia-reperfusion injury,MIRI)中舒芬太尼后处理所起的作用及其与磷脂酰肌醇-3-激酶/丝氨酸-苏氨酸激酶(1-phosphatidlylinositol 3-kinase/protein-serine-threonine kinase,PI3K/Akt)通路、m PTP的关系.方法:由山西医科大学动物中心提供的健康雄性SD大鼠53只,其中,29只体重为160~180g。糖尿病大鼠模型的制备方法是先采用高糖高脂的饲料喂养四周,再将链脲佐菌素(streptozotocin,STZ)35mg/kg注射于腹腔,造模成功的标志是血糖≥16.7mmol/l,模型造成后继续饲养2周,每周测一次血糖,取血糖≥16.7mmol/l的大鼠24只;采用随机数字表法,将糖尿病大鼠随机分为四组(n=6):糖尿病假手术组(DM-S组)、糖尿病缺血再灌注组(DM-I/R组)、糖尿病舒芬太尼后处理组(DM-SP组)和糖尿病舒芬太尼后处理+Wortmannin组(DM-SP+W组)。另取24只体重250~300g的健康正常SD大鼠,用随机数字表法,将非糖尿病大鼠随机分为四组(n=6):非糖尿病假手术组(NDM-S组)、非糖尿病缺血再灌注组(NDM-I/R组)、非糖尿病舒芬太尼后处理组(NDM-SP组)和非糖尿病舒芬太尼后处理+Wortmannin组(NDM-SP+W组)。采用结扎左冠状动脉前降支(left anterior descending coronary artery,LAD)30min,再灌注120min的方法制备大鼠心肌缺血再灌注模型。DM-S组和NDM-S组只在LAD下穿线但不结扎,DM-SP组、NDM-SP组和DM-SP+W组、NDM-SP+W组均在再灌注前5min通过舌下静脉注射舒芬太尼1.0ug/kg,DM-SP+W组和NDM-SP+W组注射舒芬太尼前先注射PI3K抑制剂Wortmannin15ug/kg。再灌注120min时采血,测定乳酸脱氢酶(lactate dehydrogenase,LDH)的活性和肌酸激酶同工酶(creatine kinase isoenzyme,CK-MB)的浓度;处死大鼠后,取心脏,测定心肌细胞凋亡指数(apoptosis index,AI),采用TUNEL法;测定心肌烟酰胺腺嘌呤二核苷酸(NAD+)含量,采用分光光度法;检测心肌组织Akt、p-Akt的表达水平,采用Western blot法。结果:与S组比较,糖尿病和非糖尿病大鼠的IR组、SP组和SP+W组LDH活性和CK-MB浓度升高、AI增加、NAD+含量降低、p-Akt/Akt的比值略增大(p0.05);与DM-I/R组比较,DM-SP组和DM-SP+W组上述指标差异无统计学意义(p0.05);与NDM-I/R组比较,NDM-SP组LDH活性和CK-MB浓度降低、AI减少、NAD+含量升高、p-Akt/Akt的比值增加(p0.05),NDM-SP+W组上述指标差异无统计学意义(p0.05);与DM-SP组比较,NDM-SP组LDH活性和CK-MB浓度降低、AI减少、NAD+含量升高、p-Akt/Akt的比值增加(p0.05)。结论:舒芬太尼后处理可通过激活PI3K/Akt通路以及减少m PTP的开放减轻非糖尿病大鼠MIRI,而舒芬太尼后处理保护大鼠免受心肌缺血再灌注损伤的作用可被2型糖尿病因素抵消,机制可能与PI3K/Akt通路没有被激活有关。
[Abstract]:Aim: to investigate the role of sufentanil in myocardial ischemia-reperfusion injury (myocardial ischemia-reperfusion injury,MIRI) in diabetic and non-diabetic rats and its relationship with phosphatidylinositol 3-kinase / serine threonine kinase (1-phosphatidlylinositol 3-kinase/protein-serine-threonine kinase,PI3K/Akt) pathway. Methods: 53 healthy male SD rats were provided by Animal Center of Shanxi Medical University. The diabetic rat model was made by feeding high sugar and high fat diet for four weeks, then injecting streptozotocin,STZ 35mg/kg into abdominal cavity. The mark of success of the model was blood glucose 鈮，

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