| 李永胜,严丽,雍永权,梁黔生.丹参酮ⅡA对高血压大鼠肥厚心肌TGF-β1/Smads信号通路的影响[J].,2010,30(5):499-503 |
| 丹参酮ⅡA对高血压大鼠肥厚心肌TGF-β1/Smads信号通路的影响 |
| Effect of Tanshinone ⅡA on the Transforming Growth Factor Beta1/Smads Signal Pathway in Rats with Hypertensive Myocardial Hypertrophy |
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| DOI： |
| 中文关键词: 丹参酮ⅡA 心肌肥厚 血管紧张素Ⅱ受体 转化生长因子β1 Smads信号蛋白 |
| 英文关键词:tanshinone ⅡA myocardial hypertrophy angiotensin Ⅱ receptor transforming growth factor β1 Smads signal protein |
| 基金项目:国家自然科学基金资助项目(No.30500657) |
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| 中文摘要: |
| 目的研究丹参酮(Tanshinone,TSN)ⅡA对压力超负荷大鼠肥厚心肌血管紧张素1型受体(angiotensin Ⅱtype 1 receptor,AT1R)、转化生长因子β1(transforming growth factor-β1,TGF-β1)与其胞内信号蛋白Smads基因表达的影响,探讨TSNⅡA抑制高血压左心室肥厚的分子机制。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模型组、丹参酮低、高剂量组[10、20mg/(kg.d)]、缬沙坦组[10mg/(kg.d)],每组8只;另有8只作为假手术组。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(left ventricular mass index,LVMI)、病理切片HE染色测量心肌纤维直径(myocardial fiber dimension,MFD);采用逆转录-聚合酶链式反应(reverse transcription-polymerase chain raction,RT-PCR)检测AT1R mRNA的表达水平,免疫印迹法(Western blot)分别检测TGF-β1及其胞内信号蛋白Smad-3、4、7的蛋白水平。结果 (1)丹参酮低、高剂量组血压没有变化,并显著高于假手术组和缬沙坦组(P<0.01)。(2)丹参酮低、高剂量组和缬沙坦组的LVMI、MFD均显著低于模型组(P<0.01)。(3)心肌肥厚时AT1R、TGF-β1和Smad-3的表达显著增加(P<0.01),高剂量TSNⅡA和缬沙坦都可使肥厚心肌的AT1R mRNA和TGF-β1、Smad-3蛋白水平明显下调(P<0.01),缬沙坦对TGF-β1的下调作用较丹参酮明显(P<0.05)。(4)低、高剂量的丹参酮和缬沙坦均可以使Smad-7蛋白的表达显著上调(P<0.01),丹参酮高剂量组上调作用明显超过缬沙坦组(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AT1R mRNA表达、阻滞TGF-β1/Smads的信号转导有关。 |
| 英文摘要: |
| Objective To investigate the molecular mechanism of tanshinone ⅡA (TSN) for preventing left ventricular hypertrophy (LVH) by studying the expressions of angiotensin Ⅱ type 1 receptor (AT1R), transforming growth factor β1 (TGF-β1) and intracellular signal protein gene (Smads gene) in the hypertrophic myocardium of hypertensive rat models induced by pressure over-loading. Methods SD rat model of LVH was established by abdominal aorta constriction. The model animals were randomly divided into 4 groups 4 weeks after modeling, the untreated model control group (C1), the two tested groups (T1 and T2) treated respectively with high (20 mg/kg) and low (10 mg/kg) dose of TSN ⅡA per day via intraperitoneal injection, and the positive control group (C2) treated with 10 mg/kg of Valsartan per day by gastric perfusion, with 8 animals in each group. Besides, 8 SD rats managed with sham operation were set up as the sham-operated control group (C3). After an 8-week treatment, the caudal arterial pressure, left ventricular mass index (LVMI), myocardial fiber dimension (MFD, by pathologic examination with HE staining) in rats were measured. Meanwhile, mRNA expression of AT1R, protein expression of TGF-β1 and activity of Smad-3,4,7 in the ventricular tissue were detected by RT-PCR analysis and Western blotting respectively. Results (1) Blood pressure in Group T1 and T2 was unchanged after treatment, which was significantly higher than that in Group C2 and C3 (P<0.01, P<0.05). (2) LVMI and MFD in Group T1, T2 and C2 were higher than that in Group C3 (P<0.01), but remarkably lower than that in Group C1 (P<0.01). (3) Levels of AT1R, TGF-β1 and Smad-3 expression increased significantly in the model rats (P<0.01), but they were down-regulated in Group T1 and C2, and the TGF-β1 regulating effect in the C2 was more potent than that in Group T1 and T2 (P<0.05). (4) Protein expression of Smad-7 was up-regulated in Goup T1, T2 and C2 obviously (P<0.01), and the effect in Group T1 was superior to that in C2 (P<0.05). Conclusion The myocardial hypertrophy inhibition effect of TSN ⅡA is a blood pressure independent process, and it may be related to the inhibition of AT1R mRNA expression and blocking of TGF β1/Smads signal pathway. |
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