粉防己碱激活Akt/GSK-3b信号通路保护心肌I/R大鼠研究  

Analysis on Tetrandrine Activating Akt/GSK-3b Signal Pathway for Protecting Myocardial I/R Rats

作　　者：张克清[1] 戴珍[1] 李彦萍[1] ZHANG Keqing;DAI Zhen;LI Yanping

机构地区：[1]安阳市中医院心内科,河南安阳455000

出　　处：《新中医》2018年第9期12-17,共6页New Chinese Medicine

基　　金：河南省中医药科学研究专项课题(2015ZY02087)

摘　　要：目的:探究粉防己碱对心肌缺血/再灌注损伤(Ischemia/Reperfusion injury,I/R)大鼠的心肌梗塞面积、心脏功能蛋白激酶B(Protein kinase B,Akt)/糖原合酶激酶-3b(Glycogen synthase kinase-3b,GSK-3b)信号通路的影响。方法:SPF级健康雄性SD大鼠180只,随机分为假手术组、模型组、辛伐他汀组及粉防己碱低、中、高剂量组。辛伐他汀组于造模前14天灌胃给予辛伐他汀2.0 mg/(kg·d);粉防己碱低、中、高剂量组于造模前20 min分别腹腔注射给予粉防己碱1.5 mg/kg、3.0 mg/kg、6.0 mg/kg;假手术组与模型组给予等体积生理盐水。通过结扎冠状动脉左前降支建立I/R大鼠模型。再灌注24 h后,测定大鼠血清肌钙蛋白T(cTnT)含量及肌酸激酶同工酶(CK-MB)、乳酸盐脱氢酶(LDH)活性;氯化硝基四氮唑蓝(NBT)染色法测定心肌梗死面积;超声心动图检测心脏功能;Western blot检测心肌组织Akt、p Akt、GSK-3b、p GSK-3b蛋白表达。结果:与假手术组比较,模型组大鼠血清cTnT含量及CK-MB、LDH活性均显著升高,心肌梗死面积显著增大,心脏左室舒张末期内径(Left ventricular internal diameter at diastole,LVIDd)和左室收缩末期内径(Left ventricular internal diameter at systole,LVIDs)均显著增大,心肌组织pAkt/Akt、p GSK-3b/GSK-3b比值均显著减小,差异均有统计学意义(P<0.0 5);与模型组比较,粉防己碱中、高剂量组及辛伐他汀组大鼠血清cTnT含量及CK-MB、LDH活性均显著降低,心肌梗死面积及心脏LVIDd、LVIDs均显著减小,心肌组织pAkt/Akt、pGSK-3b/GSK-3b比值均显著增加,且呈剂量依赖性,差异均有统计学意义(P<0.0 5)。结论:粉防己碱能明显减轻I/R大鼠的心肌损伤,改善心脏功能,其机制可能与Akt/GSK-3b通路活化有关。Objective：To discuss the effect of tetrandrine on the myocardial infarction area and cardiac-function protein kinase B（Akt）/glycogen synthase kinase-3 b（GSK-3 b） signal pathway of rats with myocardial ischemia/reperfusion injury（I/R）. Methods： 180 healthy male SD rats of SPF level were divided into the sham operation group,the model group,the simvastatin group and the groups of tetrandrine in low, middle and high doses randomly. 14 days before the model establishment, the simvastatin group was given simvastatin in 2.0 mg/（kg·d） by gavage;20 minutes before the model establishment,the groups of tetrandrine in low,middle and high doses were given tetrandrine in 1.5 mg/kg, 3.0 mg/kg and 6.0 mg/kg by intraperitoneal injection respectively; the sham operation group and the model group were given saline of the same volume. Established the model of I/R rats by ligating the left anterior descending artery. After 24 hours of perfusion, measured the content of cardiac troponin T（cTnT） and the activity of creatine kinase isoenzyme（CK-MB） in serum and lactate dehydrogenase（LDH）;measured the myocardial infarction area by nitrotetrazolum blue chloride（NBT）staining; detected cardiac function via echocardiography; detected the protein expression of Akt, pAkt, GSK-3 b and pGSK-3 b via Western blot. Results：Comparing with the sham operation group,the content of cTnT and the activity of CK-MB and LDH in serum of the model group were all significantly increased, the myocardial infarction area was significantly enlarged, left ventricular internal diameter at diastole（LVIDd） and left ventricular internal diameter at systole（LVIDs） were both increased evidently, and the ratios of pAkt/Akt and pGSK-3 b/GSK-3 b in myocardial tissue were evidently decreased,differences being significant（P〈0.05）. Comparing with the model group, the content of cTnT and the activity of CK-MB and LDH in serum of the simvastatin group and the groups of tetrandrine in middle and high doses were all significant

关 键 词：粉防己碱 缺血/再灌注损伤(I/R) 心脏功能 丝氨酸-苏氨酸蛋白激酶 糖原合酶激酶-3b(GSK-3b) 动物实验 大鼠 

分 类 号：R285.5[医药卫生—中药学]