青葙皂苷对动脉粥样硬化的影响及机制研究OACSTPCD
Study of effect and mechanism of celosins on atherosclerosis
目的 探讨青葙皂苷对动脉粥样硬化的抑制作用及其机制.方法 33 只 4 周龄ApoE-/-实验小鼠先适应性喂养1周,随机选取 22只小鼠高脂肪饮食喂养12周建立动脉粥样硬化模型,成模小鼠随机分为模型组和青葙皂苷组,每组各11只.青葙皂苷组给予腹腔注射青葙皂苷60 mg/(kg·d),模型组给予生理盐水,连续给药 12 周,12 周后处死实验小鼠并采集血液及其主动脉组织标本.采用HE染色方法观察动脉粥样斑块形成;全自动生化分析仪分别检测小鼠血清中总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)的水平;利用RT-qPCR检测小鼠主动脉组织中过氧化物酶体增殖物激活受体-α(PPAR-α)、清道夫受体以及脂质相关代谢相关基因mRNA的表达水平.结果 与模型组比较,青葙皂苷组巨噬细胞泡沫化抑制,血清中TC、TG及LDL-C的水平降低(P<0.05);HDL-C水平增加(P<0.05);主动脉组织中清道夫受体A(SR-A)及分化簇36(CD36)的表达下调(P<0.05),清道夫受体B(SR-B)的表达上调(P<0.05),导致脂质蓄积的胆固醇酰基转移酶-1(ACAT-1)、固醇调节元件结合蛋白-1C(SREBP-1C)的表达下调(P<0.05),促进脂质代谢的肉碱棕榈酰转移酶 1(CPT-1)、脂蛋白脂酶(LPL)的mRNA上调(P<0.05);并且PPAR-α的表达上调(P<0.05).结论 青葙皂苷通过激活PPAR-α信号通路调节巨噬细胞清道夫受体及脂质代谢相关基因表达,减轻组织中巨噬细胞泡沫化,抑制动脉粥样硬化的发生发展.
Objective To study the inhibitory effect of celosins on atherosclerosis and its mechanism.Methods A total of 33 4-week-old ApoE-/-mice were fed adaptively for 1 week.Twenty-two mice were randomly chosen and fed with a high-fat diet for 12 weeks to establish the atherosclerosis model,and the model mice were randomly divided into model group and celosins group,each group had 11 mice.Celosins group was given intraperitoneal injection of 60 mg/(kg·d)of celosins for 12 weeks,and model group was given normal saline for 12 weeks.After 12 weeks,the mice were killed to collect blood and aortic tissue specimens.Arterial plaque formation was observed by HE staining.Total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C)and high density lipoprotein cholesterol(HDL-C)in serum were detected by automatic biochemical analyzer.The mRNA expression levels of peroxisome proliferator-activated receptor α(PPAR-α),scavenger receptor and lipid metabolism-related genes were detected by RT-qPCR.Results Compared with model control group,the macrophage foaming in celosins group was inhibited,and serum TC,TG and LDL-C levels decreased(P<0.05),HDL-C level increased(P<0.05),the expression of scavenger receptor A(SR-A)and cluster of differentiation 36(CD36)in aortic tissue was down-regulated(P<0.05),and the expression of scavenger receptor B(SR-B)was up-regulated(P<0.05),the expression of acyl-coenzyme A:cholesterol acyltransferase-1(ACAT-1)and sterol regulatory element-binding protein-1C(SREBP-1C)that caused lipid accumulation was down-regulated(P<0.05),and the mRNA of carnitine palmitoyltransferase(CPT-1)and lipoprotein lipase(LPL)that promoted lipid metabolism was up-regulated(P<0.05),the expression of PPAR-α was up-regulated(P<0.05).Conclusion Celosins regulates the expression of scavenger receptor and lipid metabolization-related genes in macrophages by activating PPAR-α signaling pathway,alleviates the foaming of macrophages in the tissue,and inhibit the occurrence and development of atherosclerosis.
张威;徐大勇;程云涛;张学辉
274200 菏泽,山东省成武县人民医院心血管内科274200 菏泽,山东省成武县人民医院心血管内科272000 济宁,山东省济宁医学院附属医院心血管内274200 菏泽,山东省成武县人民医院心血管内科
青葙皂苷动脉粥样硬化血脂水平过氧化物酶体增殖物激活受体-α信号通路
CelosinsAtherosclerosisBlood lipid levelPeroxisome proliferator activates receptor α signaling pathway
《心脑血管病防治》 2024 (10)
10-13,31,5
山东省中医药科技项目(2021M011B-402)
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