四氢生物蝶呤改善高血压小鼠左心室舒张功能的作用及机制研究  

Effects of tetrahydrobiopterin on improve the function of left ventricular diastolic and study its mechanisms in hypertensive mice

作　　者：罗科学[1] 边杰 陈富兴[1] 

机构地区：[1]浙江省立同德医院干部保健科,杭州310012 [2]浙江大学附属邵逸夫医院国际医疗中心,杭州310032

出　　处：《中国临床药理学杂志》2018年第1期30-33,共4页The Chinese Journal of Clinical Pharmacology

摘　　要：目的研究四氢生物蝶呤(BH4)对高血压小鼠左心室舒张功能的干预作用及对磷酸化蛋白激酶B(p-Akt)表达的影响。方法以雄性C57BL/6小鼠构建高血压模型。按照体重将建模成功小鼠随机分为2组:实验组(灌胃BH4溶液10μL·g^(-1)·d^(-1))、模型组(0.9%NaCl),另选健康小鼠20只作为假手术组(0.9%NaCl),均灌胃10μL·g^(-1),均连续灌服7 d。以超声心动图检测BH4干预后小鼠的左心功能;用蛋白质免疫印迹法检测BH4干预后小鼠心肌组织中蛋白激酶B(Akt)和p-Akt蛋白的表达。结果 BH4干预后,假手术组、模型组和实验组的二尖瓣口舒张早期血流峰值速度/二尖瓣环舒张早期组织运动速度(E/E’)比值分别为25.74±5.23,38.45±3.68,32.15±5.24;这3组的左心室舒张末压(LVEDP,mmHg)分别为84.0±5.2,104.3±12.5,100.2±7.5;这3组的左心室松弛时间常数(Tau,ms)分别为10.6±0.5,14.3±0.8,12.1±0.6;这3组的左心室舒张末压力容积系数(EDPVR,mmHg·μL^(-1))分别为0.15±0.02,0.22±0.05,0.16±0.05。模型组的上述指标均高于假手术组;实验组的上述指标均低于模型组,差异均有统计学意义(P<0.05或P<0.01)。各组心肌组织的Akt蛋白表达差异无统计学意义(P>0.05);实验组的心肌组织中p-Akt蛋白表达水平高于模型组,差异有统计学意义(P<0.05)。与模型组比较,实验组的一氧化氮(NO)含量和超氧化物歧化酶(SOD)水平升高而丙二醛(MDA)水平降低,组间差异均有统计学意义(P<0.05或P<0.01)。结论 BH4可通过提高高血压小鼠心肌p-Akt表达量与降低心肌氧化应激水平,进而改善其左心室舒张功能。Objective To study the effects of tetrahydrobiopterin（ BH4） on left ventricular diastolic function and expression of phosphorylated protein kinase B（ p-Akt） in hypertensive mice. Methods Male C57BL/6 mouse were selected to construct hypertensive models, the mouse modeled successfully were randomly divided into two groups according to their weight： Experimental group（ lavage with BH4 solution10 μL·g^（-1）·d^（-1）） and model group（ lavage with normal saline）,20 healthy mouse were selected as sham operation group（ lavage with normal saline）,at dose of 10 μL·g^（-1） in three groups,all were continuously fed for 7 days. The effect of BH4 intervention on left ventricular function in mice were detected by echocardiography. The expression of Akt and p-Akt proteins in the myocardium were detected by Western blot. Results After BH4 intervention,ratio of left ventricular early diastolic fillig velocity/left ventricular early diastolic mitral annual velocity（ E/E ＇） in sham operation group,model group and experimental group were 25. 74 ± 5. 23,38. 45 ± 3. 68,32. 15 ± 5. 24,respectively; the left ventricular end diastolic pressure（ LVEDP,mmHg） in the three groups were 84. 0 ± 5. 2,104. 3 ± 12. 5,100. 2 ± 7. 5 respectively; the Tau（ ms） in the three groups were 10. 6 ± 0. 5,14. 3 ± 0. 8,12. 1 ± 0. 6,respectively; the end-diastolic pressure-volume relation（ EDPVR,mmHg·μL^（-1）） in the three groups were 0. 15 ± 0. 02,0. 22 ± 0. 05,0. 16 ± 0. 05,respectively. The factors in the model group were higher than the sham operation group; while the factors in the experimental group were lower than the model group; the differnce had significantly（ P 0. 05 or P 0. 01）. There was no significant difference in the expression of Akt protein in each group（ P 0. 05）. The expression of p-Akt protein in myocardium of experimental group was higher than that of the model group with significantly（ P 0. 05）. Compared with the model group,the levels of nitric oxide（ N

关 键 词：四氢生物蝶呤 高血压 左心室舒张功能 磷酸化蛋白激酶B 

分 类 号：R972.4[医药卫生—药品]