丹参酮ⅡA对高血压肥厚心肌细胞游离钙离子及一氧化氮合酶基因表达的影响  

Effect of tanshinoneⅡA on angiotensin receptor and free calcium ion in hypertrophic myocardium of rats due to abdominal aorta constriction

作　　者：李永胜[1] 王照华[1] 王进[1] 严丽[1] 雍永权[1] 梁黔生[1] 郑智[1] 杨光田[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院急诊科,武汉430030

出　　处：《中国急救医学》2008年第2期143-146,共4页Chinese Journal of Critical Care Medicine

基　　金：国家自然科学基金资助项目(No30500657)

摘　　要：目的通过研究丹参酮ⅡA对腹主动脉缩窄的高血压大鼠肥厚心肌血管紧张肽Ⅱ受体(ATR)基因表达及细胞内游离钙离子浓度([Ca2+]i)的影响,探讨丹参酮ⅡA逆转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假手术组(A组)、手术组(B组)、丹参酮低剂量组(C组,10mg·kg-1·d-1腹腔注射)、丹参酮高剂量组(D组,20mg·kg-1·d-1腹腔注射)及缬沙坦组(E组,10mg·kg-1·d-1灌胃)。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(LV-MI)、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AT1受体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游离Ca2+浓度的变化。结果①C、D组的血压[(188±11、187±14)mmHg]显著高于A、E组[vs(117±8、136±15)mmHg,P<0.01],C、D组与B组[(186±13)mmHg]之间差异无统计学意义(P>0.05)。②C、D组和E组的LVMI、MFD均高于A组(P<0.05),显著低于B组(P<0.01)。③B组的AT1RmRNA和蛋白的表达显著高于其他各组(P<0.01);C、D组间差异无统计学意义(P>0.05),但均高于E组(P<0.05);C、D、E组的AT1R基因表达均未降至A组水平(P<0.05)。④B组细胞内[Ca2+]i明显高于其他各组(P<0.01);D组与A组之间差异无统计学意义(P>0.05);E组和C组仍高于A、D组(P<0.05)。结论丹参酮ⅡA可通过下调心肌细胞AT1基因表达、阻止心肌细胞的钙离子内流发挥逆转心肌肥厚的作用,该作用是非血压依从性的。Objective To explore the molecular biological mechanism about tanshinone Ⅱ A reversing left ventricular hypertrophy, it would be studied how tanshinone Ⅱ A gave an impact to angiotensin receptor and free calcium ion in hypertrophic myocardium of rats due to abdominal aorta constriction. Methods SD rats were operated with abdominal aorta constriction and 8 rats were done with artificial surgery. After 4weeks, all rats were divided into 4 groups： myocardial hypertrophy group, Low dose tanshinone ⅡA group （10 mg . kg^-1 . d^-1） , high dose tanshinone ⅡA group （20 mg . kg^-1 . d^-1） and Valsartan group （10 mg . kg^-1 . d^- 1 intragastric administration）. 8 weeks later, measuring the left ventricular mass index （ LVMI ） with the tissue of left ventricle and myocardial fiber dimension （ MFD ） by pathological section and HE stain. To detect mRNA and proteins expression of AT1 receptors in left ventricular tissues of all groups by RT - PCR and Western blotting. [ Ca^2＋ ] i was observed with laser - scanning confocal microscope. Results （1） The blood pressure in group myocardial hypertrophy [ （ 186 ± 13 ） mm Hg] and tansginone 11 A [ low and high dose, （188 ± 11,187 ± 14）mm Hg] was obviously higher than that in group artificial surgery and Valsartan group [ vs （117 ± 8,136 ± 15）mm Hg, P 〈 0.01 ]. But there was no difference between group myocardial hypertrophy and group tanshinoneUA （ low and high dose ） （ P 〉 0. 05 ）（2） The LVMI and MFD were obviously higher in group tanshinone Ⅱ A （ low and high dose ） and group Valsartan than that in group artificial surgery （ P 〈 0.05 ） , and lower than group myocardial hypertrophy （P 〈0.01）. （3） The mRNA and protein＇s expression of AT1 receptor in myocardial hypertrophy group were obviously more than that in other groups（ P 〈0.01） ; there were no difference within two tanshinone Ⅱ A groups （ P 〉 0.05 ） , but tanshinone Ⅱ A groups was higher than valsartan group （ P 〈 0.05

关 键 词：丹参酮ⅡA 压力超负荷 心肌肥厚 血管紧张肽受体 游离钙离子 

分 类 号：R285.5[医药卫生—中药学]