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三种不同中药复方对动脉粥样硬化的防治作用:一项机制研究

[Prevention and Treatment of Atherosclerosis by Three Different Chinese Medical Compounds: a Mechanism Study].

作者信息

Jiang Hua, Jiang Yu-ji

出版信息

Zhongguo Zhong Xi Yi Jie He Za Zhi. 2015 Oct;35(10):1244-8.

Abstract

OBJECTIVE

To study the effect of Buyang Huanwu Decoction (BHD), Xuefu Zhuyu Decoction (XZD), and Sijunzi Decoction (SD) contained serums on expressions of Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signals, lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), tumor necrosis factor-α (TNF-α), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and to explore possible anti-atherosclerotic mechanisms.

METHODS

Twenty New Zealand rabbits were divided into 4 groups at random, i.e., the normal control group, the BHD group (6.7 g/kg), the XZD group (3.6 g/kg), and the SD group (1.6 g/kg), 5 in each group. All medication lasted for 7 successive days. Two h after the final medication, about 50 mL blood was withdrawn from rabbit heart for preparing serums. Human umbilical vein endothelial cell ECV304 were cultured in vitro for 18 h and randomly divided into the blank control group, the model group, the Western medicine (WM) control group, the BHD group, the XZD group, and the SD group at random. ECV304, except in the blank control group, were stimulated with lipopolysaccharide (LPS) for 2 h. Those in the WM control group and CM groups were treated respectively with corresponding CM contained serum for 24 h. Finally gene and protein expressions of TLR4, myeloid differentiation factor 88 (MyD88), tumor necrosis factor receptor-associated factor-6 (TRAF-6), NF-κB, LOX-1, TNF-α, ICAM-1, and VCAM-1 were detected by fluorescent quantitative PCR and Western blot.

RESULTS

Compared with the blank control group, mRNA expressions of TLR4, MyD88, TRAF-6, NF-KB, LOX-1 , TNF-cx, ICAM-1, and VCAM-1 increased significantly; protein expressions of TLR4, NF-κB, LOX-1, TNF-α, ICAM-1, and VCAM-1 also increased significantly in the model group (P < 0.01). Compared with the model group, mRNA and protein expressions of each index could be significantly inhibited in the BHD group, the XZD group, and the WM control group (P < 0.05). Besides, mRNA and protein expressions of each index could be significantly elevated more in the BHD group and the XZD group than in the WM control group (P < 0.05). No statistical difference existed in each index between the SD group and the rest groups (P > 0.05).

CONCLUSIONS

The mechanism of BHD and XZD for fighting against atherosclerosis might be associated with inhibiting TLR4/NF-κB signal transduction pathway and expressions of its downstream inflammatory factors such as LOX-1, TNF-α, ICAM-1, and VCAM-1. But SD showed no associated effect on atherosclerosis.

摘要

目的

研究补阳还五汤(BHD)、血府逐瘀汤(XZD)和四君子汤(SD)含药血清对Toll样受体4(TLR4)/核因子(NF)-κB信号通路、凝集素样氧化低密度脂蛋白受体-1(LOX-1)、肿瘤坏死因子-α(TNF-α)、血管细胞黏附分子-1(VCAM-1)、细胞间黏附分子-1(ICAM-1)表达的影响,探讨其可能的抗动脉粥样硬化机制。

方法

将20只新西兰兔随机分为4组,即正常对照组、BHD组(6.7 g/kg)、XZD组(3.6 g/kg)和SD组(1.6 g/kg),每组5只。所有药物连续给药7天。末次给药后2小时,从兔心脏取血约50 mL制备血清。人脐静脉内皮细胞ECV304体外培养18小时后,随机分为空白对照组、模型组、西药(WM)对照组、BHD组、XZD组和SD组。除空白对照组外,ECV304用脂多糖(LPS)刺激2小时。WM对照组和含药血清组分别用相应含药血清处理24小时。最后采用荧光定量PCR和蛋白质免疫印迹法检测TLR4、髓样分化因子88(MyD88)、肿瘤坏死因子受体相关因子6(TRAF-6)、NF-κB、LOX-1、TNF-α、ICAM-1和VCAM-1的基因和蛋白表达。

结果

与空白对照组相比,模型组TLR4、MyD88、TRAF-6、NF-κB、LOX-1、TNF-α、ICAM-1和VCAM-1的mRNA表达显著升高;TLR4、NF-κB、LOX-1、TNF-α、ICAM-1和VCAM-1的蛋白表达也显著升高(P < 0.01)。与模型组相比,BHD组、XZD组和WM对照组各指标的mRNA和蛋白表达均能显著抑制(P < 0.05)。此外,BHD组和XZD组各指标的mRNA和蛋白表达升高幅度显著高于WM对照组(P < 0.05)。SD组与其余各组各指标比较差异无统计学意义(P > 0.05)。

结论

BHD和XZD抗动脉粥样硬化的机制可能与抑制TLR4/NF-κB信号转导通路及其下游炎症因子如LOX-1、TNF-α、ICAM-1和VCAM-1的表达有关。但SD对动脉粥样硬化无相关作用。

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