通心络对自发性高血压大鼠心肌纤维化的影响

1、通心络对自发性高血压大鼠心肌纤维化的影响         作者：谭安雄 李小云 王玉银 李涛 封芬 【摘要】 目的探讨通心络(Tongxinluo,TXL)对自发性高血压大鼠(spontaneously hypertensive rat,SHR)心肌纤维化的影响。方法将18 只SHR随机分为通心络治疗组(TXL) 和空白对照组(SHR),每组各9 只,另9 只Wistar-Kyoto大鼠作为正常对          

2、                    作者：谭安雄李小云王玉银李涛封芬【摘要】  目的探讨通心络(Tongxinluo,TXL)对自发性高血压大鼠(spontaneously hypertensive rat,SHR)心肌纤维化的影响。方法将18 只SHR随机分为通心络治疗组(TXL) 和空白对照组(SHR),每组各9 只,另9 只Wistar-Kyoto大鼠作为正常对照组(WKY)。TXL组用

3、通心络溶于蒸馏水中配成溶液后按1.5 g·kg-1·d -1 的剂量灌胃, SHR组、WKY组均给予等量蒸馏水灌胃。1次/d，连续8周后，用M超测量舒张末期左室内径(left ventricular end-diastolic dimension ,LVEDD) 、舒张末期左室后壁厚度(left ventricular posterior walldepth,LVPWD)、舒张末期室间隔厚度(interventricular septal depth,IVSD)；超声测量室间隔的平均声学强度(average image intensity , AII1)、峰- 峰强度(pe

4、ak to peak intensity , PPI1)及其心包校正的声学强度( corrected acoustic intensity ,CAI1)；左室后壁的平均声学强度(average image intensity , AII2)、峰- 峰强度(peak to peak intensity , PPI2)及其心包校正的声学强度( corrected acoustic intensity ,CAI2)；测定左室质量指数( left ventricular mass index , LVMI)；用放射免疫法测定血清型前胶原氨基末端肽(procollagen type amino-term

5、inal propeptide, PNP)。结果TXL组大鼠LVMI、LVPWD、IVSD、AII1、AII2、CAI1、CAI2、PNP较SHR大鼠减小(P<0.05)；TXL组大鼠LVEDD、PPI1、PPI2 较SHR组增大(P< 0. 05)。结论通心络可抑制SHR心肌纤维化,改善心脏功能。 【关键词】  通心络；纤维化；大鼠；高血压Abstract：ObjectiveTo explore the effect of  Tongxinluo on myocardialfibrosis of rats with spontaneous hypertensi

6、on Methods18 rats with spontaneous hypertension (SHRs) were divided at random into two groups :Tongxinluo group (n=9) and SHR group (n=9).Another 9  Wistar-Kyoto rats served as control group .Rats in Tongxinluo group were fed with a mixture of Tongxinluo and distilled water with dosage of 1.5 g

7、·kg-1·d -1 , while other two groups were fed with distilled water at equal volume,once a week.8 weeks later, left ventricular end-diastolic dimension (LVEDD) , left ventricular posterior wall depth (LVPWD) and interventricular septal depth (IVSD) of late diastolic time were all determined

8、by ultrasonic M .The average image intensity ( AII),the peak to peak intensity (PPI) and the corrected acoustic intensity (CAI) of the interventricular septum and left ventricular posterior wall were all determined by ultrasonic, left ventricular mass index ( LVMI) was determined ,and procollagen ty

9、pe amino-terminal propeptide(PNP) was determined by radioimmunoassay . ResultsLVMI,LVPWD,IVSD,AII of the interventricular septum ,AII of left ventricular posterior wall,CAI of the interventricular septum ,CAI of left ventricular posterior wall and PNP in Tongxinluo group were lower than those in

10、0; SHR group(P < 0. 05),while LVEDD,PPI of the interventricular septum and PPI of left ventricular posterior  wall in the Tongxinluo group were higher than those in the SHR group (P < 0. 05). ConclusionTongxinluo capsule can reduce myocardial fibrosis and improve the left ventricular dias

11、tolic dysfunction induced by hypertension.Key words：Tongxinluo; Fibrosis; Rats;   Hypertension    通心络胶囊是根据中医理论研制而成的中药复方制剂,有研究发现13，通心络胶囊具有抗动脉粥样硬化、抗心肌梗塞后心室重构作用，能改善内皮功能, 对冠状动脉粥样硬化性心脏病等疾病具有很好的防治作用。本研究采用通心络对自发性高血压大鼠( spontaneously hypertensive rat, SHR)进行干预,探讨通心络对自发性高血压大鼠心肌纤维化的影响

12、，为通心络防治高血压心肌纤维化提供实验依据。1  器材1.1 动物18 只雄性SHR大鼠购于北京维通利华动物中心;9 只雄性WKY(Wistar-Kyoto)大鼠由中南大学湘雅医学院动物学部提供。均为12周龄、清洁级。1.2 药物及器材 通心络胶囊由河北石家庄以岭药业有限公司生产，批号：200608121，0.26 g/粒；型前胶原氨基末端肽(PNP)放免试剂盒购自北京北方生物技术研究所；RBP- 型电脑大鼠血压心率测定仪购于北京中日友好医院临床研究所; PHLIPS7500 型超声显像仪。2方法2.1动物分组及给药将18 只SHR大鼠随机分成通心络治疗组(TXL组）和空白

13、对照组(SHR组)，9只WKY大鼠作为对照组(WKY组)。TXL组用通心络溶于蒸馏水中配成溶液后按1.5 g·kg-1·d -1 的剂量灌胃, SHR组、WKY组均给予等量蒸馏水灌胃。连续8周，1次/d。2.2 血压和体重的测量采用RBP-型电脑大鼠血压心率测定仪在大鼠清醒状态下无创性测定尾动脉收缩压(systolic blood pressure,SBP),每2 周测1 次,同时测体质重(body mass ,BM),每次测3次，取其平均值。2.3 心脏超声检查连续用药8周后，3组大鼠均用10%水合氯醛(400 mg·kg-1)腹腔注射,麻醉后行超声检查,取大鼠

14、左室长轴切面二尖瓣水平,在二维超声影像指导下用M 超测量舒张末期左室内径(left ventricular end-diastolic dimension ,LVEDD) 、舒张末期左室后壁厚度(left ventricular posterior walldepth,LVPWD)、舒张末期室间隔厚度(interventricular septal depth,IVSD)。上述指标均连续测量3个心动周期,求其均值。2.4 背向散射积分(integral backscatter,IBS)测定取标准胸骨旁左室长轴观及心尖四腔观,进入AD-IBS状态,采集3 s的动态二维图像,记录于磁光盘供脱机分析

15、。调整仪器设置进入AD-IBS状态,读取磁光盘信息。将取样框设置适宜的大小、形状及方向,分别置于胸骨旁左室长轴观的室间隔中部、左室后壁中部及同一声束线的心包,跟踪测量部位并注意避开心内膜、心外膜,计算3个心动周期的平均值,根据图像分析结果,计算出以下声学密度值: 峰- 峰强度(peak to peak intensity,PPI),即背向散射积分周期变化幅度;图像平均强度(averageimage intensity,AII),即背向散射积分。用心肌AII和心包AII比值作为校正的声学强度( corrected acoustic intensity,CAI)。室间隔及左室后壁测量指标分别用PPI1、AII1、CAI1 和PPI2、AII2、CAI2 表示。2.5 血浆PNP测定