氯沙坦钾对自发性高血压大鼠左心室肥厚心肌线粒体蛋白的影响  

Effects of losartan potassium on myocardial mitochondrial proteins in spontaneously hypertensive rats with left ventricular hypertrophy

作　　者：孟超[1] 金贤[1] 王晓玲[2] 夏立[2] 蔡军[3] 方宁远[1] 

机构地区：[1]上海交通大学医学院附属仁济医院老年病科,上海200001 [2]上海交通大学基础医学院病理生理学教研室,上海200025 [3]上海交通大学基础医学院病理中心,上海200025

出　　处：《上海交通大学学报（医学版）》2016年第10期1425-1431,共7页Journal of Shanghai Jiao tong University:Medical Science

基　　金：上海市浦江人才计划资助项目(14PJ1406300)~~

摘　　要：目的·探讨自发性高血压大鼠(SHR)左心室肥厚心肌线粒体蛋白谱的改变及氯沙坦钾降压治疗对SHR左心室肥厚心肌线粒体蛋白的影响。方法·20周龄SHR(SHR组)随机分为8周氯沙坦钾降压组(治疗组,28周龄)及未用药组(对照组,28周龄),并以20周龄Wistar-Kyoto(WKY)大鼠作为SHR组的对照(WKY组)。应用荧光定量蛋白质组学的方法检测各组大鼠左心室组织线粒体蛋白质表达谱,同时测定各组大鼠血压及心肌直径。结果·与WKY组比较,SHR组大鼠左心室心肌线粒体的蛋白质表达谱共有13个蛋白质点发生改变,变化均在1.3倍以上;将这些点从预制胶上切下后进行消化和质谱分析,许多点被鉴定出是同一种蛋白,所鉴定出的5种蛋白均涉及线粒体的能量代谢。降压治疗8周后,与对照组比较,治疗组左心室心肌线粒体蛋白表达谱未发现新的差异点;治疗组收缩压和舒张压均明显降低(P=0.000,P=0.002),增大的左心室心肌细胞直径显著缩短(P=0.000)。结论·SHR高血压心肌肥厚存在线粒体能量代谢障碍,氯沙坦钾能明显改善SHR的血压并部分逆转左心室肥厚,但对线粒体能量代谢蛋白无明显影响。提示这些线粒体差异蛋白可能并非由高血压后负荷所致。Objective·To explore changes in myocardial mitochondrial proteinogram in spontaneously hypertensive rats （SHR） with left ventricular hypertrophy （LVH） and to investigate the effects of losartan potassium anti-hypertensive treatment on the proteinogram. Methods·20-week-old SHRs （SHR group） were randomly assigned to the 8-week losartan potassium anti-hypertensive treatment group （therapy group, 28-week-old） and the untreatment group （control group, 28-week-old）. Wistar-Kyoto （WKY） rats aged 20 weeks were used as the controls of the SHR group （WKY group）. Left ventricular mitochondrial proteinogram was measured using two-dimensional fluorescence difference gel electrophoresis （2D-DIGE） combined with MALDI-TOF/TOF tandem mass spectrometry. Blood pressure and myocardial diameter of rats were also measured. Results·Thirteen mitochondrial protein spots showed alterations by more than 1.3 folds in the SHR group compared with the WKY group. Some spots were identified as the same protein by digestion and mass spectrometry analysis. Five identified proteins were all related to the energy metabolism of mitochondria. No additional different spots were identified after 8 weeks of anti-hypertensive treatment. The therapy group had significantly lower systolic blood pressure and diastolic blood pressure than the control group （P=0.000, P=0.002） and remarkably shorter myocardial diameter in enlarged left ventricles （P=0.000）. Conclusion·SHRs with LVH have mitochondrial energy metabolism dysfunction. Losartan potassium can significantly decrease the blood pressure and partially reverse LVH, but has no significant effect on mitochondrial energy metabolism proteins, suggesting changes in mitochondrial proteins are possibly not caused by the load after hypertension.

关 键 词：线粒体 自发性高血压大鼠 左心室肥厚 氯沙坦钾 降压治疗 

分 类 号：R544.1[医药卫生—心血管疾病]