通心絡對自發(fā)性高血壓大鼠心肌纖維化的影響

1、通心絡對自發(fā)性高血壓大鼠心肌纖維化的影響         作者：譚安雄 李小云 王玉銀 李濤 封芬 【摘要】 目的探討通心絡(Tongxinluo,TXL)對自發(fā)性高血壓大鼠(spontaneously hypertensive rat,SHR)心肌纖維化的影響。方法將18 只SHR隨機分為通心絡治療組(TXL) 和空白對照組(SHR),每組各9 只,另9 只Wistar-Kyoto大鼠作為正常對          

2、                    作者：譚安雄李小云王玉銀李濤封芬【摘要】  目的探討通心絡(Tongxinluo,TXL)對自發(fā)性高血壓大鼠(spontaneously hypertensive rat,SHR)心肌纖維化的影響。方法將18 只SHR隨機分為通心絡治療組(TXL) 和空白對照組(SHR),每組各9 只,另9 只Wistar-Kyoto大鼠作為正常對照組(WKY)。TXL組用

3、通心絡溶于蒸餾水中配成溶液后按1.5 g·kg-1·d -1 的劑量灌胃, SHR組、WKY組均給予等量蒸餾水灌胃。1次/d，連續(xù)8周后，用M超測量舒張末期左室內徑(left ventricular end-diastolic dimension ,LVEDD) 、舒張末期左室后壁厚度(left ventricular posterior walldepth,LVPWD)、舒張末期室間隔厚度(interventricular septal depth,IVSD)；超聲測量室間隔的平均聲學強度(average image intensity , AII1)、峰- 峰強度(pe

4、ak to peak intensity , PPI1)及其心包校正的聲學強度( corrected acoustic intensity ,CAI1)；左室后壁的平均聲學強度(average image intensity , AII2)、峰- 峰強度(peak to peak intensity , PPI2)及其心包校正的聲學強度( corrected acoustic intensity ,CAI2)；測定左室質量指數(shù)( left ventricular mass index , LVMI)；用放射免疫法測定血清型前膠原氨基末端肽(procollagen type amino-term

5、inal propeptide, PNP)。結果TXL組大鼠LVMI、LVPWD、IVSD、AII1、AII2、CAI1、CAI2、PNP較SHR大鼠減小(P<0.05)；TXL組大鼠LVEDD、PPI1、PPI2 較SHR組增大(P< 0. 05)。結論通心絡可抑制SHR心肌纖維化,改善心臟功能。 【關鍵詞】  通心絡；纖維化；大鼠；高血壓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    通心絡膠囊是根據(jù)中醫(yī)理論研制而成的中藥復方制劑,有研究發(fā)現(xiàn)13，通心絡膠囊具有抗動脈粥樣硬化、抗心肌梗塞后心室重構作用，能改善內皮功能, 對冠狀動脈粥樣硬化性心臟病等疾病具有很好的防治作用。本研究采用通心絡對自發(fā)性高血壓大鼠( spontaneously hypertensive rat, SHR)進行干預,探討通心絡對自發(fā)性高血壓大鼠心肌纖維化的影響

12、，為通心絡防治高血壓心肌纖維化提供實驗依據(jù)。1  器材1.1 動物18 只雄性SHR大鼠購于北京維通利華動物中心;9 只雄性WKY(Wistar-Kyoto)大鼠由中南大學湘雅醫(yī)學院動物學部提供。均為12周齡、清潔級。1.2 藥物及器材 通心絡膠囊由河北石家莊以嶺藥業(yè)有限公司生產(chǎn)，批號：200608121，0.26 g/粒；型前膠原氨基末端肽(PNP)放免試劑盒購自北京北方生物技術研究所；RBP- 型電腦大鼠血壓心率測定儀購于北京中日友好醫(yī)院臨床研究所; PHLIPS7500 型超聲顯像儀。2方法2.1動物分組及給藥將18 只SHR大鼠隨機分成通心絡治療組(TXL組）和空白

13、對照組(SHR組)，9只WKY大鼠作為對照組(WKY組)。TXL組用通心絡溶于蒸餾水中配成溶液后按1.5 g·kg-1·d -1 的劑量灌胃, SHR組、WKY組均給予等量蒸餾水灌胃。連續(xù)8周，1次/d。2.2 血壓和體重的測量采用RBP-型電腦大鼠血壓心率測定儀在大鼠清醒狀態(tài)下無創(chuàng)性測定尾動脈收縮壓(systolic blood pressure,SBP),每2 周測1 次,同時測體質重(body mass ,BM),每次測3次，取其平均值。2.3 心臟超聲檢查連續(xù)用藥8周后，3組大鼠均用10%水合氯醛(400 mg·kg-1)腹腔注射,麻醉后行超聲檢查,取大鼠

14、左室長軸切面二尖瓣水平,在二維超聲影像指導下用M 超測量舒張末期左室內徑(left ventricular end-diastolic dimension ,LVEDD) 、舒張末期左室后壁厚度(left ventricular posterior walldepth,LVPWD)、舒張末期室間隔厚度(interventricular septal depth,IVSD)。上述指標均連續(xù)測量3個心動周期,求其均值。2.4 背向散射積分(integral backscatter,IBS)測定取標準胸骨旁左室長軸觀及心尖四腔觀,進入AD-IBS狀態(tài),采集3 s的動態(tài)二維圖像,記錄于磁光盤供脫機分析

15、。調整儀器設置進入AD-IBS狀態(tài),讀取磁光盤信息。將取樣框設置適宜的大小、形狀及方向,分別置于胸骨旁左室長軸觀的室間隔中部、左室后壁中部及同一聲束線的心包,跟蹤測量部位并注意避開心內膜、心外膜,計算3個心動周期的平均值,根據(jù)圖像分析結果,計算出以下聲學密度值: 峰- 峰強度(peak to peak intensity,PPI),即背向散射積分周期變化幅度;圖像平均強度(averageimage intensity,AII),即背向散射積分。用心肌AII和心包AII比值作為校正的聲學強度( corrected acoustic intensity,CAI)。室間隔及左室后壁測量指標分別用PPI1、AII1、CAI1 和PPI2、AII2、CAI2 表示。2.5 血漿PNP測定