丹参酮ⅡA磺酸钠盐抑制腹主动脉缩窄高血压大鼠的心肌肥厚

Tanshinone ⅡA Inhibit Pressure Load Induced Left Ventricular Hypertrophys and Myocardial JAK1/STAT3 in Rats

背景左心室肥厚是独立于血压意外的心血管危险因素,容易导致心肌缺血、心律失常和猝死。JAK/STAT通路已经被证实参与了心肌肥大和增生的过程。丹参酮ⅡA是丹参中最丰富、结构最具有代表性的丹参酮,能拮抗心肌细胞的Ca2+内流,降低左心室心肌中肿瘤坏死因子α(TNF-α)以及原癌基因c-fos、Bcl-2以及p53蛋白的表达。目的观察丹参酮ⅡA磺酸钠盐(STS)并与缬沙坦比较其对腹主动脉缩窄高血压大鼠左心室肌肥厚的作用以及对Janus激酶及转录的信号转导子及激活子(JAK/STAT)的影响。方法24只9周龄Spraque-Dauley(SD)大鼠,环扎其腹主动脉,制成高血压大鼠的模型,分为心肌肥厚组(n=8)、丹参酮ⅡA组[10mg/(kg·d),n=8]和缬沙坦组[10mg/(kg·d),n=8];另选8只年龄和性别相匹配的SD大鼠为假手术组。测量大鼠的尾动脉收缩压(SBP)及左心室质量指数(LVMI)。应用HE染色、VG染色检测心肌细胞的直径,采用Western blot方法测定各组大鼠心肌JAK1和STAT3的表达。结果与假手术组相比,心肌肥厚组的SBP[假手术组:(117.3±8.3)比心肌肥厚组:(186.5±13.5)mmHg,P<0.05]、LVMI[假手术组(1.60±0.03)比心肌肥厚组(2.1±0.1)mg/g,P<0.05]和心肌细胞的直径(MFD)[假手术组(10.2±0.9)比心肌肥厚组(18.1±1.3)μm,P<0.05]均显著增加。JAK1[假手术组(0.32±0.04)比心肌肥厚组(0.69±0.16),P<0.05]、STAT3[假手术组:(0.55±0.14)比心肌肥厚组:(0.74±0.08),P<0.05]的表达也明显升高。与心肌肥厚组相比,丹参酮ⅡA和缬沙坦能降低JAK1与STAT3的表达[JAK1(心肌肥厚组:0.69±0.16比丹参酮ⅡA组:0.63±0.16比缬沙坦组:0.46±0.07,P<0.05;STAT3(心肌肥厚组:0.74±0.08比丹参酮ⅡA组:0.70±0.06比缬沙坦组:0.59±0.08,P<0.05)]。结论JAK/STAT的表达在心肌肥厚的信号通路中起着重要的作用。丹参酮ⅡA与缬沙坦抑制左室肥厚的进展可能与降低JAK、STAT3的表达有关。

Background Left ventricular hypertrophy（LVH） is a cardiovascular risk factor independent of the blood pressure. JAK/STAT pathway has been confirmed to participate in cardiac hypertrophy and hyperplasia. Our previous reports have shown that sodium tanshinone ⅡA sulfonate（STS） reversed LVH, inhibited the myocardial cells Ca^2＋ influx, lowered left ventricular myocardial tumor necrosis factor-α（TNF-α）and the proto-oncogene c-fos, Bcl-2, and p53 protein expression. Objective To study the effect of sodium tanshinone Ⅱ A sulfonate（STS） on JAK/STAT pathway in left ventricular hypertrophy（LVH） induced by abdominal aorta stenosis in rats. Methods Twenty-four 9-weeks-old rats submitted to abdominal aorta constriction, were randomized to receive STS 10 mg/（kg · d）（n=8）or sterilized distilled water （1 mL/d）（n=8）, or valsartan 10 mg/（kg · d） by gavage（n=8）, with age and sex matched sham operated rats（n=8） as control. HE, VG and immunohistonchemical staining were used to evaluate the myocardial fiber dimension（MFD）. Expressions of JAK1 and STAT3 were assessed by using Western blot. Results Compared with the control group, pressure loaded rats had higher SBP [（117.3±8.3） vs LVH： （186. 5±13. 5）mmHg, P〈0.05], LVMI[（1.60±0.03） vs LVH：（2.1±0.1）mg/g, P〈0.05], MFD[（10.2±0.9） vs LVH： （18.1±1.3）μm, P〈0.05], JAKl [（ 0. 32 ± 0. 04 ） vs LVH： （0.69±0.16）, P〈0.05]and STAT3[（0.55±0.14） vs LVH： （0.74±0.08）, P〈0.05]. STS and valsartandecrease JAKI[（0. 69±0.16） vs STS： （0.63±0.16） vs valsartan.. （0.46±0.07）, P〈0.05land STAT3 expres7 sions[（0. 74!0. 08） vs STS.. （0.70±0.06） vs valsartan.. （0.59± 0.08）, P〈0.05]. Conclusion Long-term use of STS or Valsartan inhibit the development of LVH which is associated with decreasing the expression of JAK1, STAT3.