磷脂酰肌醇3激酶/丝氨酸苏氨酸蛋白激酶信号通路对异丙肾上腺素所致大鼠心肌损伤的作用

目的通过使用盐酸异丙肾上腺素(ISO)制备心肌损伤模型,探讨磷脂酰肌醇3激酶/丝氨酸苏氨酸蛋白激酶(PI3K/AKT)信号通路是否参与心肌损伤的发病机制。方法 20只雄性Wistar大鼠随机分成心肌损伤模型组(ISO组)和对照组。ISO组大鼠每天背部皮下注射ISO 20 mg.kg-1.d-1,对照组大鼠每天注射等量9 g.L-1盐水,均连续注射7 d。采用全自动生化检测仪检测2组大鼠血浆中乳酸脱氢酶(LDH)、肌酸激酶(CK)和α-羟丁酸脱氢酶(α-HBDH)水平。采用蛋白印迹法定量检测大鼠心肌组织中PI3K、p85-PI3K、p55-PI3K、AKT及p-AKT蛋白表达。结果与对照组比较,ISO组大鼠血浆LDH、CK及α-HBDH水平均显著上升,差异有统计学意义(Pa<0.05),证明采用ISO建模成功;与对照组比较,ISO组大鼠心肌组织中PI3K和AKT蛋白水平未见明显变化,但其磷酸化p85-PI3K、p55-PI3K和p-AKT蛋白水平均显著上调,差异有统计学意义(Pa<0.05)。结论在ISO所致的心肌损伤中,PI3K和AKT的磷酸化水平上调,PI3K/AKT信号通路参与ISO所致心肌损伤的发病机制。

Role of Phosphoinositide 3 - Kinase/Serine - Threonine Protein Kinase Pathway in Pathogenesis of Isoproterenol -Induced Myocardial Injury in Rats

Objective To explore whether the phosphoinositide 3-kinase/serine-threonine protein kinase(PI3K/AKT) signaling pathway was related to the mechanism of isoproterenol(ISO)-induced myocardial injury. Methods Twenty male Wistar rats were randomly divided into ISO group and control group.In ISO group,the rats were administered with ISO of 20 mg·kg-1·d-1 via subcutaneous injection while in the control group,the rats were administered with saline via subcutaneous injection.The duration of the above mentioned treatment was 7 days.The levels of lactate dehydrogenase(LDH),creatine kinase(CK) and alpha-hydroxybutyrate dehydrogenase(α-HBDH) in plasma of rats in the 2 groups were detected by using automatic biochemical detector.PI3K,p85-PI3K,p55-PI3K,AKT and p-AKT protein expressions in myocardial tissue were detected by using Western-blot method. Results Plasma LDH,CK and α-HBDH levels increased significantly in ISO group compared with control group(Pa<0.05),which suggested that the myocardial injury model was made successfully.There were no statistically significant differences in PI3K and AKT protein expressions between ISO group and control group,while p85-PI3K,p55-PI3K and p-AKT protein expressions increased significantly in ISO group compared with control group(Pa<0.05). Conclusions The phosphorylation levels of PI3K and AKT increase in rats with ISO-induced myocardial injury,and PI3K/AKT signaling pathway may be related to the mechanism of ISO-induced myocardial injury.