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传统中药通心络剂量依赖性增强易损斑块的稳定性:与高剂量辛伐他汀治疗的比较。

Traditional Chinese medication Tongxinluo dose-dependently enhances stability of vulnerable plaques: a comparison with a high-dose simvastatin therapy.

机构信息

The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Shandong University Qilu Hospital, Jinan, No. 107, Wen Hua Xi Road, Jinan, Shandong, 250012, PR China.

出版信息

Am J Physiol Heart Circ Physiol. 2009 Dec;297(6):H2004-14. doi: 10.1152/ajpheart.00208.2009. Epub 2009 Oct 2.

DOI:10.1152/ajpheart.00208.2009
PMID:19801495
Abstract

This study was carried out to test the hypothesis that Tongxinluo (TXL) as a Chinese herbal medicine enhances stability of vulnerable plaque dose dependently via lipid-lowering and anti-inflammation effects, similar to a high-dose simvastatin therapy. After abdominal aortic balloon injury, 75 rabbits were fed a 1% cholesterol diet for 10 wk and were then divided into five groups for 8-wk treatment: control group, low-dose TXL group, moderate-dose TXL group, high-dose TXL group, and high-dose simvastatin group. At the end of week 16, an adenovirus containing p53 was injected into the abdominal aortic plaques. Two weeks later, plaque rupture was induced by pharmacological triggering. The incidence of plaque rupture in all treatment groups (14.3%, 7.1%, 7.7%, and 7.1%) was significantly lower than that in control group (73.3%; P>0.01). TXL dose-dependently lowered serum lipid levels and inhibited systemic inflammation. Corrected acoustic intensity and fibrous cap thickness of the aortic plaques were significantly increased, whereas plaque area, plaque burden, vulnerable index, and expression of oxidized low-density lipoprotein (ox-LDL) receptor 1, matrix metalloproteinase 1 (MMP-1), MMP-3, tissue inhibitor of MMP 1, and NF-kappaB in plaques were markedly reduced in all treatment groups when compared with the control group. Similar to high-dose simvastatin group, high-dose TXL group exhibited a low serum level of low-density lipoprotein cholesterol and ox-LDL, a low expression level of systemic and local inflammatory factors and a low plaque vulnerability index, with no differences in the incidence of plaque rupture among all treatment groups. TXL dose-dependently enhances the stability of vulnerable plaques and prevents plaques from rupture. Simvastatin and TXL offer similar protection in terms of lipid-lowering, anti-inflammation, and antioxidation effects.

摘要

本研究旨在验证以下假说

作为一种中药,通心络(TXL)通过降脂和抗炎作用,剂量依赖性地增强易损斑块的稳定性,类似于高剂量辛伐他汀治疗。腹主动脉球囊损伤后,75 只兔子喂食 1%胆固醇饮食 10 周,然后分为 5 组进行 8 周治疗:对照组、低剂量 TXL 组、中剂量 TXL 组、高剂量 TXL 组和高剂量辛伐他汀组。在第 16 周结束时,将含有 p53 的腺病毒注入腹主动脉斑块中。2 周后,通过药理学触发诱导斑块破裂。所有治疗组(14.3%、7.1%、7.7%和 7.1%)的斑块破裂发生率明显低于对照组(73.3%;P>0.01)。TXL 剂量依赖性地降低血清脂质水平并抑制全身炎症。校正后的主动脉斑块声强和纤维帽厚度明显增加,而斑块面积、斑块负荷、易损指数以及斑块中氧化型低密度脂蛋白(ox-LDL)受体 1、基质金属蛋白酶 1(MMP-1)、MMP-3、基质金属蛋白酶抑制剂 1 和 NF-κB 的表达明显降低在与对照组相比,所有治疗组。与高剂量辛伐他汀组相似,高剂量 TXL 组表现出低血清低密度脂蛋白胆固醇和 ox-LDL 水平、全身和局部炎症因子表达水平低以及斑块易损指数低,而所有治疗组的斑块破裂发生率无差异。TXL 剂量依赖性地增强易损斑块的稳定性并防止斑块破裂。辛伐他汀和 TXL 在降脂、抗炎和抗氧化作用方面提供相似的保护。

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