活血解毒中药对动脉粥样硬化小鼠斑块稳定性、血脂及DNA甲基化水平的影响

目的研究血府逐瘀胶囊、四季三黄胶囊及其联合应用对动脉粥样硬化（As）小鼠主动脉斑块稳定性、血脂及血清DNA甲基化水平的影响。方法对ApoE基因敲除小鼠予高脂饮食喂养13周后随机分组，后再继续喂养13周，同时给予药物治疗。处死采血，检测血脂、血清DNA甲基化及甲基化转移酶（DNMTs）水平，并取出心脏及主动脉，石蜡包埋，取主动脉根部的第3切面，行HE染色，经IPP图像分析，测量并计算主动脉As斑块纤维帽的平均厚度及斑块内细胞外脂质占斑块面积的百分比。结果与模型组相比，辛伐他汀组、血府逐瘀胶囊组、四季三黄胶囊组和联合应用组小鼠主动脉斑块的平均纤维帽厚度明显增加，差异有统计学意义（P〈0．05）；与血府逐瘀胶囊组和四季三黄胶囊组相比，联合应用组的平均纤维帽厚度明显增加，差异有统计学意义（P〈0．05）。与模型组比较，辛伐他汀组、血府逐瘀胶囊组、四季三黄胶囊组和联合应用组小鼠主动脉斑块内细胞外脂质成分占斑块面积的百分比明显降低，差异有统计学意义（P〈0．05）。与模型组比较，辛伐他汀组、血府逐瘀胶囊组、四季三黄胶囊组和联合应用组小鼠甘油三酯（TG）水平明显降低（P〈0．05）。仅辛伐他汀组血清LDL—C和Tc水平降低，差异有统计学意义（P〈0．05），其余给药组差异均无统计学意义（P〉0．05）。经ELISA法检测，给药13周后，辛伐他汀组、血府逐瘀胶囊组、四季三黄胶囊组和联合应用组小鼠血清DNA甲基化水平和DNMTs水平明显升高，差异有统计学意义（P〈0．05），但组间比较差异无统计学意义（P〉0．05）。结论血府逐瘀胶囊、四季三黄胶囊及其联合应用均具有降低血清TG水平，稳定As斑块的作用，其机制可能与提高血清中DNA甲基化水平和DNMTs水平有关。

Effects of promoting-blood and detoxication Chinese medicine on plaque stability,blood lipid and methylation level of DNA in mice with atherosclerosis

Objective To explore the effects of Xuefu Zhuyu Capsule, Siji Sanhuang Capsule and their combination use on aorta plaque stability, blood lipid and methylation level of DNA in mice with atherosclerosis. Methods The mice lacking ApoE gene were treated with high-fat diet for 13 weeks and then randomly divided into groups. Then the mice were fed for another 13 weeks, during which the treatment was given. Mter sacrificed, the blood samples of mice were collected to test the level of blood lipid, methylation of DNA and DNA methyltransferase （DNMT）. Also the heart and aorta were taken out; with paraffin embedding, the third section of aortic root was taken and stained with HE. After IPP image analysis, the average thickness of fibrous cap of atherosclcrosis plaque and percentage of extracellular lipid to plaque area were measured and calculated. Results Compared with the model group, the average thickness of fibrous cap was obviously increased in the simvastatin group, Xuefu Zhuyu Capsule group, Siji Sanhuang Capsule group and combined use group （P 〈 0. 05 ）. Compared with Xuefu Zhuyu Capsule group and Siji Sanhuang Capsule group, the average thickness of fibrous cap was obviously increased in the combined use group （ P 〈 0. 05 ）. Compared with the model group, the percentage of extracellular lipid to plaque area was obviously lowered in the simvastatin group, Xuefu Zhuyu Capsule group, Siji Sanhuang Capsule group and combined use group （ P 〈 0. 05 ）. Compared with the model group, the level of triglyceride in the simvastatin group, Xuefu Zhuyu Capsule group, Siji Sanhuang Capsule group and combined use group was obviously lowered （P 〈 0. 05）. Only the level of LDL-C and TC in the simvastatin group was lowered （P 〈 0. 05） while the differences in the rest treatment group was not statistically significant （P 〉 0. 05）. After measurement of ELISA, the methylation of DNA and DNMT were obviously increased in the simvastatin group, Xuefu Zhuyu Capsule group, Siji Sanhuang Capsule group and combined use group, but no statistical differences were seen among different groups （P 〉 0. 05 ）. Conclusion The Xuefu Zhuyu Capsule, Siji Sanhuang Capsule and their combination use could lower the level of TG and stabilize atherosclerosis plaque, which is likely to be related with increasing the level of the methylation of DNA and DNMT.