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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。
Objective To study the effects of Xuefu Zhuyu Capsule and Sijihuanghuang Capsule on the stability of aortic plaque, serum lipids and serum DNA methylation in atherosclerotic As (AS) mice. Methods ApoE knockout mice were fed with high-fat diet for 13 weeks and then were randomly divided into groups. After that, mice were fed for another 13 weeks and given drug therapy. Blood samples were collected for blood test, serum DNA methylation and DNA methyltransferase (DNMTs) levels were measured. The heart and aorta were removed and embedded in paraffin. The third section of the aortic root was taken and stained with HE. , Measuring and calculating the average thickness of aortic As plaque fiber cap and the percentage of extracellular lipid in the plaque to plaque area. Results Compared with the model group, the mean fibular cap thickness of aortic plaque in simvastatin group, Xuefu Zhuyu Capsule group, Sijihuanghuang capsule group and combination group significantly increased (P < 0.05). Compared with Xuefuzhuyu capsule group and Sijihuanghuang capsule group, the average fiber cap thickness of the combination group increased significantly (P <0.05). Compared with the model group, the percentage of extracellular lipid components in plaque area of simvastatin group, Xuefuzhuyu capsule group, Sijihuanghuang capsule group and combination group mice significantly decreased, the difference was statistically Significance (P <0.05). Compared with the model group, the levels of triglyceride in simvastatin group, Xuefuzhuyu capsule group, Sijihuanghuang capsule group and combination group were significantly decreased (P <0.05). Serum levels of LDL-C and TC in simvastatin group were significantly lower than those in simvastatin group (P <0.05). There was no significant difference among other groups (P> 0.05). After 13 weeks of administration, the levels of DNA methylation and DNMTs in simvastatin group, Xuefuzhuyu capsule group, Sijihuanghuang capsule group and combination group were significantly increased by ELISA (P <0.05), but there was no significant difference between the two groups (P> 0.05). Conclusion Xuefu Zhuyu Capsule, Sijihuanghuang Capsule and their combination have the effect of lowering serum TG level and stabilizing As plaque. The mechanism may be related to the increase of DNA methylation level and DNMTs level in serum.