Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, PR China.
Phytomedicine. 2010 Dec 15;18(1):58-64. doi: 10.1016/j.phymed.2010.06.002. Epub 2010 Jul 16.
The adaptive changes that develop in the pressure-overloaded left ventricular myocardium include cardiac hypertrophy and interstitial fibrosis. The objectives of the present study were to evaluate the effects of Tanshinone II-A, a bioactive diterpene quinone isolated from Danshen, on cardiac fibrosis and collagen metabolism in rats with renovascular hypertension. Male Sprague-Dawley rats were subjected to two-kidney two-clip (2K2C) or sham operation (sham) and treated with Valsartan (Val, 26.7 mg/kg/d), Tanshinone II-A (Tsn, 70, 35 mg/kg/d) or vehicle. Six weeks later, systolic blood pressure (BP), LV weight, collagen abundance, cardiac function parameters, hydroxyproline content and mRNA levels of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 were evaluated. Both high-dose (Tsn-H, 70 mg/kg/d) and low-dose (Tsn-L, 35 mg/kg/d) of Tsn failed to attenuate 2K2C-induced BP elevation but significantly attenuated the attendant interstitial fibrosis. Val suppressed elevations of BP and left ventricular systolic pressure (LVSP) in 2K2C rats. Val and Tsn-H exerted comparable suppressive effects on the gene expression of MMP-9 and TIMP-1, while Val decreased the MMP-2 mRNA level without affecting the transcript levels of TIMP-2. Both Val and Tsn-H attenuated cardiac dysfunction, while Tsn-L showed slight improvement. These data demonstrate for the first time, that Tsn prevented cardiac fibrosis and improved cardiac function in a rat model of renovascular hypertensive independent of hypotensive effect. Tsn conferred its beneficial effects on the collagen metabolism probably through its regulation of transcript levels of the MMPs/TIMPs balance.
压力超负荷引起的左心室心肌适应性改变包括心肌肥厚和间质纤维化。本研究的目的是评价丹参酮 IIA（丹参中的一种生物活性二萜醌）对两肾两夹型高血压大鼠心肌纤维化和胶原代谢的影响。雄性 Sprague-Dawley 大鼠接受两肾两夹（2K2C）或假手术（假手术），并给予缬沙坦（Val，26.7mg/kg/d）、丹参酮 IIA（Tsn，70、35mg/kg/d）或载体处理。6 周后，评估收缩压（BP）、LV 重量、胶原含量、心功能参数、羟脯氨酸含量以及基质金属蛋白酶（MMP）-2、MMP-9、金属蛋白酶组织抑制剂（TIMP）-1 和 TIMP-2 的 mRNA 水平。高剂量（Tsn-H，70mg/kg/d）和低剂量（Tsn-L，35mg/kg/d）的 Tsn 均不能减轻 2K2C 引起的血压升高，但明显减轻了伴随的间质纤维化。Val 抑制 2K2C 大鼠的血压和左心室收缩压（LVSP）升高。Val 和 Tsn-H 对 MMP-9 和 TIMP-1 的基因表达具有相似的抑制作用，而 Val 降低了 MMP-2 的 mRNA 水平，而不影响 TIMP-2 的转录水平。Val 和 Tsn-H 均改善了心功能障碍，而 Tsn-L 仅略有改善。这些数据首次表明，Tsn 可预防压力超负荷大鼠的心肌纤维化并改善心功能，而与降压作用无关。Tsn 通过调节 MMPs/TIMPs 平衡的转录水平对胶原代谢产生有益作用。
