【摘要】：目的:探討在糖尿病和非糖尿病大鼠心肌缺血再灌注損傷(myocardial ischemia-reperfusion injury,MIRI)中舒芬太尼后處理所起的作用及其與磷脂酰肌醇-3-激酶/絲氨酸-蘇氨酸激酶(1-phosphatidlylinositol 3-kinase/protein-serine-threonine kinase,PI3K/Akt)通路、m PTP的關系.方法:由山西醫(yī)科大學動物中心提供的健康雄性SD大鼠53只,其中,29只體重為160~180g。糖尿病大鼠模型的制備方法是先采用高糖高脂的飼料喂養(yǎng)四周,再將鏈脲佐菌素(streptozotocin,STZ)35mg/kg注射于腹腔,造模成功的標志是血糖≥16.7mmol/l,模型造成后繼續(xù)飼養(yǎng)2周,每周測一次血糖,取血糖≥16.7mmol/l的大鼠24只;采用隨機數字表法,將糖尿病大鼠隨機分為四組(n=6):糖尿病假手術組(DM-S組)、糖尿病缺血再灌注組(DM-I/R組)、糖尿病舒芬太尼后處理組(DM-SP組)和糖尿病舒芬太尼后處理+Wortmannin組(DM-SP+W組)。另取24只體重250~300g的健康正常SD大鼠,用隨機數字表法,將非糖尿病大鼠隨機分為四組(n=6):非糖尿病假手術組(NDM-S組)、非糖尿病缺血再灌注組(NDM-I/R組)、非糖尿病舒芬太尼后處理組(NDM-SP組)和非糖尿病舒芬太尼后處理+Wortmannin組(NDM-SP+W組)。采用結扎左冠狀動脈前降支(left anterior descending coronary artery,LAD)30min,再灌注120min的方法制備大鼠心肌缺血再灌注模型。DM-S組和NDM-S組只在LAD下穿線但不結扎,DM-SP組、NDM-SP組和DM-SP+W組、NDM-SP+W組均在再灌注前5min通過舌下靜脈注射舒芬太尼1.0ug/kg,DM-SP+W組和NDM-SP+W組注射舒芬太尼前先注射PI3K抑制劑Wortmannin15ug/kg。再灌注120min時采血,測定乳酸脫氫酶(lactate dehydrogenase,LDH)的活性和肌酸激酶同工酶(creatine kinase isoenzyme,CK-MB)的濃度;處死大鼠后,取心臟,測定心肌細胞凋亡指數(apoptosis index,AI),采用TUNEL法;測定心肌煙酰胺腺嘌呤二核苷酸(NAD+)含量,采用分光光度法;檢測心肌組織Akt、p-Akt的表達水平,采用Western blot法。結果:與S組比較,糖尿病和非糖尿病大鼠的IR組、SP組和SP+W組LDH活性和CK-MB濃度升高、AI增加、NAD+含量降低、p-Akt/Akt的比值略增大(p0.05);與DM-I/R組比較,DM-SP組和DM-SP+W組上述指標差異無統(tǒng)計學意義(p0.05);與NDM-I/R組比較,NDM-SP組LDH活性和CK-MB濃度降低、AI減少、NAD+含量升高、p-Akt/Akt的比值增加(p0.05),NDM-SP+W組上述指標差異無統(tǒng)計學意義(p0.05);與DM-SP組比較,NDM-SP組LDH活性和CK-MB濃度降低、AI減少、NAD+含量升高、p-Akt/Akt的比值增加(p0.05)。結論:舒芬太尼后處理可通過激活PI3K/Akt通路以及減少m PTP的開放減輕非糖尿病大鼠MIRI,而舒芬太尼后處理保護大鼠免受心肌缺血再灌注損傷的作用可被2型糖尿病因素抵消,機制可能與PI3K/Akt通路沒有被激活有關。
[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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