高盐加速诱导的高血压性左心室重塑与基质金属蛋白酶基因表达的关系  

Relationship between hypertensive left ventricular remodeling with accelerated induction of high salt and the gene expression level of matrix metalloproteinase

作　　者：杨国红[1] 周欣[1] 刘军翔[1] 孙婧[1] 姬文婕[1] 李玉明[1] YANG Guo-hong ZHOU Xin LIU Jun-xiang SUN Jing JI Wen-jie LI Yu-ming(Institute of Cardiovascular Disease and Heart Center, Affiliated Hospital, Logistics University of PAP, Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Tianjin 300162, China)

机构地区：[1]武警后勤学院附属医院心脏中心心血管病研究所天津市心血管重塑与靶器官损伤重点实验室,天津300162

出　　处：《武警后勤学院学报（医学版）》2017年第7期553-558,共6页Journal of Logistics University of PAP（Medical Sciences）

基　　金：国家自然科学基金项目(81600328);天津市自然科学基金项目(16JCQNJC11800);武警后勤学院中心实验室开放基金项目(2015ZXKF11);武警后勤学院附属医院种子基金项目(FYM201533)

摘　　要：【目的】探讨高盐加速诱导的高血压性左室重塑由代偿向失代偿心肌肥大过渡阶段,基质金属蛋白酶/组织金属蛋白酶抑制剂(metalloproteinases/tissue inhibitors of metalloproteinases,MMPs/TIMPs)基因表达水平变化的规律。【方法】7周龄雄性自发性高血压大鼠(spontaneously hypertensive rats,SHR)及京都Wistar大鼠(wistar kyoto rats,WKY)大鼠按饮食中的盐浓度随机分为低盐组(0.5%Na Cl)和高盐组(8%Na Cl),干预12周。所有大鼠以标准的尾压法测定无创尾压,并于处死前进行血流动力学测定;采用Realtime PCR测定大鼠心肌组织MMPs/TIMPs mRNA表达水平的变化;以苦味酸-天狼星红染色观察心肌组织纤维化程度;以麦芽胚凝集素荧光染色计算心肌细胞横截面积。【结果】高盐干预结束时SHR高盐组无创尾压显著高于其它3组(P<0.05),而各组心率没有显著差异(P>0.05);SHR高盐组体质量(body mass,BM)显著低于SHR低盐组及WKY低盐组,差异有统计学意义(P<0.05);与其它3组相比,左室质量(left ventricular mass,LVM)及左室质量指数(LVM index,LVMI)均显著增高(P<0.05);有创血流动力学检测结果显示,SHR高盐组平均动脉压(mean arterial blood pressure,MAP)显著高于WKY组(P<0.05),反映左室收缩功能的d P/dtmax及主动舒张功能的d P/dt min显著高于WKY组而低于SHR低盐组(P<0.05),反映左室被动舒张功能的左室舒张末期压(left ventricular end diastolic pressure,LVEDP)显著增高(P<0.05);Realtime PCR结果显示,SHR高盐组MMP-2、MMP-9、TIMP-1及TIMP-2 mRNA表达水平显著高于其它3组(P<0.05),MMP-13、MMP-14亦有增高的趋势,但结果无统计学意义(P>0.05);PSR染色结果显示高盐干预12周SHR高盐组出现心肌间质和血管周明显的纤维化,胶原容积分数及血管周胶原面积/血管腔面积均显著高于其它3组(P<0.05);WGA荧光染色显示SHR高盐组心肌细胞横截面积亦显著高于其它3组(P<0.05)。【结论】高盐干预12周MMPs/TIMPs基因表【Objective】To explore the change of gene expression levels of metalloproteinases（MMPs）/tissue inhibitors of MMPs（TIMPs） during hypertensive left ventricular（LV） remodeling transition from compensate to decompensate hypertrophy with accelerated induction of high salt.【Methods】According to the salt concentration in the diet,7-week-old male spontaneously hypertensive rats（SHR） and wistar-kyoto rats（WKY） were randomized to receive0.5% Na Cl（low salt,LS） and 8% Na Cl（high salt,HS） for 12 weeks.Noninvasive tail blood pressure was measured by tail cuff method.All rats were anesthetized for invasive hemodynamic measurement and then sacrificed.The mRNA expression levels of MMPs/TIMPs in rat myocardial tissues were determined by realtime PCR.Myocardial fibrosis degree was observed by chrysolepic acid-sirius red staining.Myocardial cross-sectional area was calculated under wheat germ agglutinin fluorescence staining.【Results】After the high salt intervention,the noninvasive tail blood pressure in the HS-SHR group was significantly higher than those in other 3 groups（P〈0.05）,but there was no difference in heart rate（P〉0.05）.The body mass（BM） in the HS-SHR group was significantly lower than those in the LS-SHR and LS-WKY groups（P〉0.05）.Compared with other 3 groups,LV mass（LVM） and LVM index（LVMI） in the HS-SHR group increased obviously（P〈0.05）.The results of invasive hemodynamics indicated that mean arterial blood pressure（MAP） in the HS-SHR group was significantly higher than those in WHY groups（P〈0.05）.The d P/dt max for left ventricular systolic function and d P/dt min for active diastolic function were significantly higher than those in WKY groups and lower than that in LS-SHR group（P〈0.05）.Left ventricular end diastolic pressure（LVEDP） for passive diastolic function significantly increased.The results of realtime PCR showed that mRNA expression levels of MMP-2,MMP-9,TIMP-1 and TIMP-2 in the HS-SHR group were all significantly h

关 键 词：高盐 高血压 左室重塑 基质金属蛋白酶 组织金属蛋白酶抑制剂 

分 类 号：R363[医药卫生—病理学]