丹参酮ⅡA对压力超负荷大鼠肥厚心肌血管紧张素受体的影响

作者	单位
李永胜	华中科技大学同济医学院附属同济医院急诊科
王照华	华中科技大学同济医学院附属同济医院急诊科
王进	华中科技大学同济医学院附属同济医院急诊科
严丽	华中科技大学同济医学院附属同济医院急诊科
雍永权	华中科技大学同济医学院附属同济医院急诊科
梁黔生	华中科技大学同济医学院附属同济医院急诊科
郑智	华中科技大学同济医学院附属同济医院急诊科
杨光田	华中科技大学同济医学院附属同济医院急诊科

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中文摘要:

目的通过研究丹参酮ⅡA(丹参酮)对腹主动脉缩窄的高血压大鼠肥厚心肌血管紧张素Ⅱ受体(ATR)基因表达及细胞内游离钙离子浓度(〔Ca2+〕i)的影响,探讨其抑制高血压左心室肥厚的分子生物学机制。方法SD大鼠行腹主动脉缩窄术建立高血压左室心肌肥厚模型,术后4周将手术大鼠随机分为手术对照组、丹参酮低剂量组〔10mg/(kg.d)腹腔注射〕、丹参酮高剂量组〔20mg/(kg.d)腹腔注射〕及缬沙坦组〔10mg/(kg.d)灌胃〕,另有8只SD大鼠作为假手术组。用药8周后检测各组尾动脉压,取左心室组织检测左心室质量指数(LVMI)、病理切片HE染色测量心肌纤维直径(MFD);采用逆转录-聚合酶链式反应(RT-PCR)、免疫印迹法(Westernblot)分别检测AT1R、AT2R的mRNA和蛋白的表达水平。利用激光共聚焦显微镜测定心肌细胞内〔Ca2+〕i的变化。结果(1)低、高剂量的丹参酮均对升高的血压无影响,仍显著高于假手术组和缬沙坦组(P<0.01,P<0.05)。(2)丹参酮低、高剂量组和缬沙坦组的LVMI、MFD高于假手术组(P<0.05),显著低于手术对照组(P<0.01)。(3)低、高剂量的丹参酮和缬沙坦均下调手术大鼠心肌的AT1RmRNA和蛋白的表达(P<0.05);丹参酮低、高剂量对AT1R的影响不及缬沙坦(P<0.05)。(4)缬沙坦组的AT2RmRNA和蛋白表达水平较其他各组升高(P<0.05),其他各组之间差异无统计学意义(P>0.05)。(5)丹参酮低、高剂量与缬沙坦均可使肥厚心肌的〔Ca2+〕i显著降低,高剂量丹参酮对〔Ca2+〕i的影响明显超过缬沙坦组(P<0.05)。结论丹参酮ⅡA对心肌肥厚的抑制作用是非血压依赖性的,其对高血压心肌肥厚的抑制作用可能与抑制心肌细胞AT1R的mRNA、蛋白表达、阻止心肌细胞的钙离子内流有关;AT2R有可能参与了缬沙坦降低血压、逆转心肌肥厚的作用。

英文摘要:

Objective To explore the molecular biological mechanism of tanshinoneⅡA(TSN) in preventing hypertensive left ventricular hypertrophy(HLVH) through studying the effects of TSN on angiotensin receptor(ATR) expression and free calcium ion(〔Ca2+〕i) in rats with hypertrophic myocardium caused by abdominal aorta constriction.Methods SD rats were established into HLVH model by abdominal aorta constriction operation,they were randomly divided into the model group,the three treated groups treated respectively with intra peritoneal injection of low dose TSN(10 mg/kg) and high dose TSN(20 mg/kg) and gastrogavage of Valsartan(10 mg/kg) once a day 4 weeks after modeling.Besides,8 sham-operated SD rats were set up as the control group.Eight weeks later,rats’ caudal arterial pressure was measured,and their hearts were taken for measuring the left ventricular mass index(LVMI) and myocardial fiber diameter(MFD) by HE stain of the pathological section.Moreover,the mRNA and protein expressions of AT1 and AT2 receptors in the left ventricular tissue were detected by RT-PCR and Western blot,and 〔Ca2+〕i concentration was determined with laser-scanning confocal microscope.Results(1) The elevated blood pressure in the TSN treated groups,either high or low dose,remained unchanged,significantly higher than that in the control group and the Valsartan treated group(P<0.01,P<0.05).(2) LVMI and MFD in the three treated groups were significantly lower than those in the model group(P<0.01),respectively,although they were higher than those in the control group(P<0.05).(3) The mRNA and protein expressions of AT1 receptor were obviously lower in the three treated groups than those in the model groups(P<0.05);but the lowering was more significant in the valsartan treated group(P<0.05).(4) The mRNA and protein expressions of AT2 receptor were significantly higher in the Valsartan treated group as compared with other groups(P<0.05),while the difference among the other groups showed no statistical significance(P>0.05).(5) The elevated 〔Ca2+〕i concentration in hypertrophic myocardium after modeling was significantly lowered after treatment in the three treated groups(P<0.05),but the lowering in the high TSN treated group was more significant than that in the Valsartan treated group(P<0.05).Conclusion The inhibition of TSN on myocardial hypertrophy is blood pressure independent,its mechanism is possibly related with the inhibition on AT1R gene expression and the blocking of free calcium ion influx in cardiac muscle cells.AT2 receptor may participate the effect of Valsartan in lowering blood pressure and reversing myocardial hypertrophy.

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