Zhou Ming-xue, Xu Hao, Chen Ke-ji
Department of National Integrative Medicine Center for Cardiovasicular Diseases, China Academy of Chinese Medical Sciences, Beijing.
Zhongguo Zhong Xi Yi Jie He Za Zhi. 2008 Feb;28(2):126-30.
To observe the effects of active ingredients from Chinese drugs for activating blood circulation and detoxicating, including notoginseng saponins (drug 1), Coptis chinensis (drug 2), giant knotweed rhizome (drug 3) and rhubarb (drug 4), on blood lipids and inflammatory reaction of aortic atherosclerotic plaques in ApoE knockout mice.
ApoE knockout mice were fed with high-fat diet for 26 weeks, then they were randomized into 6 groups, the untreated model group and the test groups treated with various test drugs respectively. After ending the 13 weeks of treatment, all the mice were sacrificed with their blood lipids detected, and their heart and aorta were taken out to make slices with paraffin embedding. Four sections from aortic root of each mouse were chosen to measure and calculate the percentage of lipid core (LC) in the total area of plaque (TP) and the lipid/collagen ratio (L/C) in the plaque by HE and Movat staining respectively, and the mean value of the four sections was taken for analysis. The expressions of granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-alpha) in mice's aorta root were determined by immunohistochemical staining as well.
After being treated for 13 weeks, either the percentage of LC in TP and the L/C ratio was significantly lower in all the test drug treated groups than those in the model group, respectively (P < 0.01), especially prominent in the group treated with drug 3. Although lowering of the two indexes presented in all the 3 groups treated by drug 1, 2 and 3, significant difference still presented between drug 3 treated group vs drug 1 and 2 treated group (P < 0.05). As for the expressions of GM-CSF and TNF-alpha, in comparing with the untreated model group, significant decreasing of the TNF-alpha showed only in the drug 4 treated group, while that of GM-CSF could be found in all the test drug treated groups (P < 0.05).
All the 4 drugs tested in the recommended dosage can stabilize the vulnerable plaques in ApoE knockout mice by improving the constitution of plaque, among them, drug 3 and 4, the drugs possess both the actions of activating blood circulation and detoxicating, show more significant effect, and their mechanisms may be related to their actions in regulating lipid metabolism and inhibiting inflammatory reaction.
观察活血化瘀解毒类中药有效成分三七总皂苷(药物1)、黄连(药物2)、虎杖(药物3)和大黄(药物4)对载脂蛋白E基因敲除(ApoE基因敲除)小鼠血脂及主动脉粥样硬化斑块炎症反应的影响。
将ApoE基因敲除小鼠高脂喂养26周后,随机分为6组,即未处理模型组和分别用各种受试药物处理的试验组。治疗13周结束后,处死所有小鼠,检测血脂,并取出心脏和主动脉,进行石蜡包埋切片。选取每只小鼠主动脉根部的4个切片,分别通过苏木精-伊红(HE)染色和莫瓦特(Movat)染色测量并计算脂质核心(LC)在斑块总面积(TP)中的百分比以及斑块中的脂质/胶原蛋白比值(L/C),取4个切片的平均值进行分析。同时通过免疫组织化学染色测定小鼠主动脉根部粒细胞-巨噬细胞集落刺激因子(GM-CSF)和肿瘤坏死因子-α(TNF-α)的表达。
治疗13周后,各受试药物处理组的TP中LC百分比和L/C比值均分别显著低于模型组(P<0.01),其中以药物3处理组最为突出。虽然药物1、2和3处理的3组均呈现这两个指标降低,但药物3处理组与药物1和2处理组之间仍存在显著差异(P<0.05)。至于GM-CSF和TNF-α的表达,与未处理模型组相比,仅药物4处理组的TNF-α显著降低,而所有受试药物处理组的GM-CSF均降低(P<0.05)。
所测试的4种药物在推荐剂量下均可通过改善斑块构成来稳定ApoE基因敲除小鼠的易损斑块,其中药物3和4这两种具有活血化瘀解毒作用的药物效果更为显著,其机制可能与它们调节脂质代谢和抑制炎症反应的作用有关。