越鞠保和丸联合辛伐他汀对动脉粥样硬化小鼠心肌纤维化的作用

Effect of Yue-Ju Bao-He Pill And Simvastatin on Myocardial Fibrosis in Atherosclerotic Mice

目的:观察越鞠保和丸联用辛伐他汀能否增强对动脉粥样硬化引起的心肌纤维化的逆转作用。方法:采用高脂饲料饲养ApoE-/-小鼠建立动脉粥样硬化斑块模型和心肌纤维化模型,越鞠保和丸和辛伐他汀联用和单用对ApoE-/-小鼠进行干预,同时设立高脂饲料饲养的模型对照组和普通饲料饲养的正常对照组,Elisa法检测小鼠血清血脂、血管紧张素Ⅱ(AngⅡ)、基质金属蛋白酶-1(MMP-1)含量,心肌组织masson染色定量分析胶原容积分数(CVF),高通量转录组测序分析各组心肌组织差异表达基因。结果:越鞠保和丸和辛伐他汀联用相比单用能更有效的降低总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)、AngⅡ和升高高密度脂蛋白(HDL-C)、MMP-1,并且masson染色CVF值也明显降低,从高通量转录组测序差异基因分析结果来看,越鞠保和丸联合辛伐他汀与正常对照组相比,差异基因表达主要集中在脂肪酸代谢、延长及降解等相关通路上,而与模型对照组相比,差异基因表达主要集中在原发性免疫缺陷和肠道免疫网络的IgA的产生等相关通路上。结论:越鞠保和丸联合辛伐他汀可以更有效的逆转动脉粥样硬化导致的心肌纤维化,其机制与调控免疫炎性反应有关。

This study was aimed to observe the effect of Yue-Ju Bao-He（YJBH） pill and simvastatin on the reversal of myocardial fibrosis induced by atherosclerosis（AS）. ApoE-/-mice were fed on high fat diet to establish models of atherosclerotic plaque and myocardial fibrosis. YJBH pill and simvastatin were used alone or in combination as interventions. Control groups of high fat diet as well as normal diet were observed. Serum lipid and vascular angiotensin Ⅱ（Ang Ⅱ）, matrix metalloproteinase-1（MMP-1） were measured by Elisa. Quantitative analysis of collagen volume fraction（CVF） was conducted by myocardial tissue Masson staining. High-throughput transcriptome sequencing analysis was also adapted to detect differentially expressed genes in myocardial tissues of each group. The results showed that compared with single usage, YJBH pill combined with simvastatin can effectively reduce the total cholesterol（TC）,triglyceride（TG）, low density lipoprotein（LDL-C） and Ang Ⅱ, increase high density lipoprotein（HDL-C）, MMP-1, while Masson staining CVF value was also significantly decreased. Compared with the control group of normal diet, the analysis results from high-throughput transcriptome sequencing analysis showed that difference of gene expression of YJBH pill combined with simvastatin group was mainly in fatty acid metabolism, extend and degradation related pathways, and compared with the model group, the difference of gene expression was mainly in primary immunodeficiency and intestinal immune network IgA production pathways. It was concluded that the combined therapy of YJBH pill and simvastatin can effectively reverse the AS induced myocardial fibrosis. Its mechanism is related to the regulation of immune inflammatory reaction.