糖原合成酶激酶-3β与转化生长因子-β1在慢性充血性心力衰竭中的变化

Expression of hippocampus of glycogen synthase kinase-3β and transforming growth factor-β1 in rats with chronic heart failure

目的研究糖原合成酶激酶-3β(glycogen synthase kinase-3β,GSK-3β)和转化生长因子-β1(transforminggrowth factor-β1,TGF-β1)在大鼠压力超负荷性心力衰竭发生过程中的变化。方法将25只成年雄性SD大鼠随机分为正常组5只,假手术组10只,模型组10只,假手术组和模型组观察时间点为术后1周、2周、4周、8周。采用腹主动脉部分缩窄术,建立大鼠慢性充血性心力衰竭模型。应用超声心动图动态监测左心室舒张末期内径(left ventricular end-diastolic dimension,LVEDd),舒张末期室间隔厚度(interventricular septal thickness,IVST)和左心室后壁厚度(left ventricular posterior wall thickness,LVPWT);解剖心脏,计算心质量指数;免疫印迹技术检测GSK-3β和P-GSK-3β的变化,免疫组织化学染色法检测TGF-β1表达变化。结果模型组术后1周LVEDd、IVST和LVPWT分别为(4.87±0.26)mm、(2.04±0.11)mm和(1.93±0.19)mm;此后呈进行性增加趋势,术后8周分别达(6.94±0.12)mm、(2.98±0.21)mm、(3.63±0.18)mm,均高于正常组和假手术组,差异有统计学意义(P<0.01);假手术组上述指标各观察点之间比较无明显变化(P>0.05)。模型组术后8周心质量指数和左心室质量指数均高于正常组和假手术组,差异有统计学意义(P<0.01)。正常组、假手术组、模型组心肌GSK-3βWestern blotting灰度值无明显区别;模型组术后8周心肌细胞p-GSK-3βWestern blotting灰度值明显高于正常组和假手术组(P<0.05)。模型组心肌组织TGF-β1免疫组织化学检测的表达量明显高于正常组和假手术组,差异有统计学意义(P<0.05)。线性回归分析提示p-GSK-3β和TGF-β1表达与左心室质量指数存在线性相关。结论压力超负荷性心力衰竭发生过程中同时出现p-GSK-3β和TGF-β1表达的增高。

Objectives To investigate the expression of hippocampus of glycogen synthase kinase-3β （GSK-3β） and transforming growth factor-β1 （TGF-β1） in rats with chronic heart failure. Methods Totally 25 adult male SD rats were randomly assigned to 3 groups： normal group （n=5）, sham operation group （n=10） and model group （n=10）. Observation time of sham operation group and model group was 1 week, 2 weeks, 4 weeks and 8 weeks after operation. Chronic heart failure model was established by abdominal aortic constriction. Left ventricular end-diastolic dimension （LVEDd）, interventricular septal thickness （IVST） and left ventricular posterior wall thickness （LVPWT） were monitored by ultrasound cardiography. Cardiac mass index, GSK-3β and TGF-β protein expression in hippoeampal area were measured. Results LVEDd, IVST and LVPWT of model group 1 week after operation were （4.87±0.26） mm, （2.04± 0.11 ） mm and （1.93 ±0.19） mm respectively, and they showed an increasing tendency afterwards, reaching to （6.94±0.12） mm, （2.98±0.21） mm and （3.63±0.18） mm 8 weeks after operation, significantly higher than those of normal group and sham operation group （P〈0.01）. LVEDd, IVST and LVPWT of sham operation group had no significant differences at different time points （P〉0.05）. Cardiac mass index and left ventricular mass index of model group were significantly higher than those of normal group and sham operation group （P〈0.01）. Western blotting values of GSK-313 among normal group, sham operation group and model group had no significant differences （P〉0.01）. Western blotting value of p-GSK-3β in model group 8 weeks after operation was significantly higher than those of normal group and sham operation group （P〈0.05）. Express of TGF-β of model group was significantly higher than those of normal group and sham operation group （P〈0.05）. Linear regression analysis indicated that expressions of p-GSK-3β and TGF-β1 had linear correlations with left ventricular mass index. Conclusions Proteins of p-GSK-3β and TGF-β1 in the hippocampus increase during the pathophysiologic processes of heart failure.