机构地区:[1]山东第一医科大学附属省立医院心内科,山东济南250021 [2]南京大学生命科学院,江苏南京210023 [3]海北藏族自治州第二人民医院,青海海北810399
出 处:《药学研究》2025年第4期340-344,共5页Journal of Pharmaceutical Research
基 金:山东省自然科学基金项目(No.ZR2020MH028);山东省医药卫生科技发展计划项目(No.2019WS509);藏药然那桑培丸稳定动脉粥样硬化斑块机制研究项目(山东省对口支援青海干部管理组);芫根提取物对于高原性肺动脉高压作用及其机制研究项目(山东省对口支援青海干部管理组)。
摘 要:目的探讨藏药然那桑培丸(Rannasangpei,RNSP)在干预动脉粥样硬化斑块中的作用及其相关机制。方法选用6~8周龄的雄性载脂蛋白E敲除(Apolipoprotein E-knocknout,ApoE^(-/-))小鼠,采用高脂饲料喂养以建立动脉粥样硬化模型。将成功建模的小鼠随机分为模型组(仅饲喂高脂饲料)、阿托伐他汀(Atorvastatin)组{阿托伐他汀[10 mg·(kg·d)^(-1)]灌胃给药}、RNSP组{然那桑培丸[7 mg·(kg·d)^(-1)]灌胃给药},每组10只。通过油红O染色评估主动脉粥样硬化面积和主动脉根部斑块横截面积、斑块内的脂质成分。天狼猩红染色用于评估胶原成分。CD68、α-SMA免疫组化分别用于定量分析巨噬细胞、平滑肌成分。此外,计算不同组别小鼠的斑块易损指数。结果模型组、RNSP组、Atorvastatin组的初始体重差异无统计学意义(P>0.05)。与模型组相比,Atorvastatin组呈现预期血脂调控效应,而RNSP组未显示血脂改善;RNSP组与Atorvastatin组主动脉弓病变呈缓解趋势;RNSP组与Atorvastatin组动脉硬化病变面积缩减(P<0.05)。与模型组相比,RNSP组与Atorvastatin组都能提升斑块结构稳定性,并降低斑块的易损指数(P<0.05)。结论藏药然那桑培丸可通过多靶点调控发挥抗动脉粥样硬化作用,为藏医药临床转化提供新的科学依据和理论支持。Objective To investigate the role and mechanism of the Tibetan medicine Rannasangpei(RNSP)in stabilizing atherosclerotic plaques.Methods Male Apolipoprotein E-knocknout(ApoE^(-/-))mice aged 6~8 weeks were fed a high-fat diet to establish atherosclerotic models.ApoE^(-/-)male mice fed with normal diet were taken as blank control group(n=10),and the established atherosclerotic models mice were randomly divided into model group(fed with high-fat diet,n=10),Atorvastatin group[10 mg·(kg·d)^(-1)atorvastatin administered intragastrically,n=10]and RNSP group[7 mg·(kg·d)^(-1)RNSP administered intragastrically,n=10].The atherosclerotic area of aorta,the cross-sectional area of aortic root plaque and the lipid composition in plaque were estimated by oil red O staining.Sirius red staining was used to evaluate collagen composition.CD68 andα-SMA immunohistochemistry were used to quantitatively analyze the components of macrophages and smooth muscle,respectively.In addition,we calculated the plaque vulnerability index of different groups of mice.Results No significant difference in initial weight among model group,RNSP group and Atorvastatin group(P>0.05).Compared with the model group,Atorvastatin group showed the expected blood lipid regulation effect,while RNSP group did not show significant blood lipid improvement;The aortic arch lesions in RNSP group and Atorvastatin group showed a significant remission trend;The area of atherosclerotic lesions in RNSP group and Atorvastatin group was significantly reduced(P<0.05).Compared with the model group,RNSP and Atorvastatin groups significantly improved the structural stability of plaque and significantly reduced the vulnerability index of plaque(P<0.05).Conclusion The Tibetan medicine RNSP could exert its anti-atherosclerosis effect through multi-target regulation,providing new scientific basis and theoretical support for the clinical transformation of Tibetan medicine.
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