丹参酮ⅡA对自发性高血压大鼠左心室肥厚心肌细胞凋亡蛋白的作用

Effect of tanshinone ⅡA on myocardial cell apoptosis protein of spontaneously hypertensive rats with left ventricular hypertrophy

目的:观察丹参的脂溶性成分丹参酮ⅡA对自发性高血压大鼠左室肥厚心肌凋亡蛋白的作用。方法:实验于2005-03/2005-07在华中科技大学同济医学院急诊科实验室完成。①选用8周龄自发性高血压大鼠18只。随机将大鼠分为3组:对照组、丹参酮组、高血压组,每组6只。②对照组:饲养至第8周处死;丹参酮组:从饲养至第8周开始,丹参酮ⅡA(中国药品生物制品检定所,批号S02001300,1kg/包)以1mL/(kg·d)剂量腹腔注射,持续用药10周,第18周处死;高血压组:以相同容量蒸馏水替代丹参酮ⅡA腹腔注射,余同丹参酮组。③用药结束后用MRS2Ⅲ型大鼠电脑血压心率测量仪测量大鼠清醒状态下尾动脉收缩压。④处死后,迅速取出心脏,称量左心室(包括室间隔)的湿重,计算左室质量指数犤左室质量(mg)/体质量(g)犦。⑤采用免疫印迹法检测心肌细胞Bcl-2,Bax及p53蛋白表达。⑥计量资料差异比较采用单因素方差分析。结果:自发性高血压大鼠18只均进入结果分析。①高血压组大鼠左心室心肌组织Bcl-2蛋白表达明显低于对照组(t=2.405,P<0.05),而p53和Bax蛋白表达明显高于对照组(t=14.51,10.26,P<0.01)。丹参酮组Bcl-2表达明显高于高血压组(t=2.359,P<0.05),而p53和Bax蛋白表达明显少于高血压组(t=11.74,7.13,P<0.01)。②高血压组大鼠的收缩压和左室质量指数明显高于对照组(t=6.68,3.84,P<0.01),左室质量指数明显高于丹参酮组(t=2.80,P<0.05)。结论:长期应用丹参酮ⅡA治疗可预防自发性高血压大鼠左室肥厚的形成,其机制可能与丹参酮ⅡA上调心肌细胞凋亡蛋白Bcl-2、下调Bax蛋白及抑制p53蛋白的表达有关。

AIM： To observe the effect of tanshinone Ⅱ A （TSN- Ⅱ A） on myocardial cell apoptosis protein of spontaneously hypertensive rats with left ventricular hypertrophy. METHODS： The experiment was completed in the Laboratory of Emergency Department of Tongji Medical College Affiliated to Huazhong University of Science and Technology from March to July 2005. ① Totally 18 spontaneously hypertensive rats with 8 weeks old were divided randomly into three groups： control group, TSN group and hypertension group with 6 in each group. ② Control group： Rats were killed after 8 weeks. TSN group： 1 mL/（kg.d） TSN-Ⅱ A （China Pharmacy Biological Products Examination Institute, batch number： S02001300, 1 kg/bag） was injected into rats in TSN group at the beginning of the 8^th week for 10 successive weeks, and all rats were killed in tbe 18^th week. Hypertension group： Distilled water of the same volume of TSN-Ⅱ A was injected intraperitoneally, and other processes were as the same as those in TSN group. ③ After medication, systolic blood pressure （SBP） of caudal artery of rats at wakefulness was measured with MRS2 Ⅲ computer blood pressure ＆ heart rate measurement. ④ Heart was obtained rapidly to measure wet mass of left ventricle （including interventricular septum） and calculate left ventricular mass index （LVMI） [mass of left ventricle （mg）/body mass （g）]. ⑤ Myocardial cell Bcl-2, Bax and p53 expression were assessed with Western blot. ⑥ Measurement data were compared with one-way analysis of variance. RESULTS： Totally 18 spontaneously hypertensive rats entered the final analysis. ① Expression of Bcl-2 protein in myocardial tissue of left ventricle of rats was lower in hypertension group than that in control group （t=2.405, P 〈 0.05）, but expressions of p53 and Bax protein were higher than those in control group （t=14.51, 10.26, P 〈 0.01）. Bcl-2 expression in TSN group was higher than that in hypertension group （t=2.359, P 〈 0.05）, but expressions of p53 and Bax protein were lower than those in hypertension group （t=1 1.74,7.13, P 〈 0.01）. ② Systolic pressure and LVMI were higher in hypertension group than those in control group （t =6.68, 3.84, P〈 0.01）, and LVMI was also higher than that in TSN group （t=2.80, P 〈 0.05）, CONCLUSION： long-term usage of TSN can inhibit the development of LVH in spontaneously hypertensive rats. The mechanism may be related with up-regulating the expression of Bcl-2 and down-regulating the expression of Bax and p53 by TSN- Ⅱ A.