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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 is a cardiovascular risk factor that is independent of accidental blood pressure and can easily lead to myocardial ischemia, arrhythmias, and sudden death. The JAK / STAT pathway has been shown to be involved in cardiac hypertrophy and hyperplasia. Tanshinone IIA is the most abundant and structurally representative tanshinone in Salvia miltiorrhiza. It can antagonize the influx of Ca2 + in myocardial cells and decrease the levels of tumor necrosis factor alpha (TNF-alpha) and proto-oncogene c-fos and Bcl-2 in left ventricular myocardium As well as p53 protein expression. Objective To observe the effects of sodium tanshinone Ⅱ A sulfonate (STS) and valsartan on hypertrophy of left ventricular hypertrophy in rats with hypertensive abdominal aorta and the effects of Janus kinase and its transcriptional activator (JAK) / STAT). Methods Twenty-four Spraque-Dauley (SD) rats, aged 9 weeks, were cerclage the abdominal aorta, and were divided into three groups: hypertrophic myocardium (n = 8), tanshinone ⅡA group D), n = 8] and valsartan group [10 mg / (kg · d), n = 8]. Eight SD rats of the same age and sex were selected as the sham operation group. The tail artery systolic pressure (SBP) and left ventricular mass index (LVMI) of rats were measured. The diameter of myocardial cells was detected by HE staining and VG staining. The expression of JAK1 and STAT3 in myocardium of each group was determined by Western blot. Results Compared with the sham-operation group, SBP in sham operation group (117.3 ± 8.3) was significantly higher than that in myocardial hypertrophy group (186.5 ± 13.5 mmHg, P <0.05) (2.1 ± 0.1) mg / g, P <0.05], and the diameter of myocytes (MFD) in the sham operation group (10.2 ± 0.9 vs 18.1 ± 1.3 μm, P <0.05) A significant increase. (P <0.05); STAT3 [sham operation group: (0.55 ± 0.14) vs. Myocardial hypertrophy group: (0.74 ± 0.08), P <0.05 for sham operation group (0.32 ± 0.04 vs 0.69 ± 0.16, ] Expression is also significantly increased. Tanshinone IIA and valsartan decreased the expression of JAK1 and STAT3 compared with those in cardiac hypertrophy group [JAK1 (0.69 ± 0.16 vs 0.33 ± 0.16 vs 0.46 ± 0.07, P < 0.05); STAT3 (0.76 ± 0.08 vs 0.37 ± 0.06 vs 0.5% vs valsartan group, P <0.05) .Conclusion The expression of JAK / STAT plays an important role in the signal pathway of cardiac hypertrophy An important role.Tanshinone Ⅱ A and valsartan inhibition of left ventricular hypertrophy may be related to the reduction of JAK, STAT3 expression.