基于SENP1分子探讨冠心康通过胆固醇逆向转运改善动脉粥样硬化的机制  

Mechanism of Guanxinkang in improving atherosclerosis through reverse cholesterol transport based on the SENP1 molecule

作　　者：张一凡 丁洁 杜敏[1,2] 冯骁腾 刘萍 ZHANG Yi-fan;DING Jie;DU Min;FENG Xiao-teng;LIU Ping(Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China;Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学附属龙华医院,上海200032 [2]上海中医药大学,上海201203

出　　处：《中华中医药杂志》2022年第5期2903-2907,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.81873117)。

摘　　要：目的:观察冠心康对LDLR-/-小鼠及RAW264.7细胞胆固醇逆向转运的影响。方法:将LDLR-/-小鼠随机分为对照组、模型组,冠心康-低、中、高剂量组。除对照组外,其余组给予高脂饲料喂养12周后,以相应0.9%氯化钠溶液或药物灌胃12周。RAW264.7细胞、si-SENP1-RAW264.7细胞用氧化型低密度脂蛋白(ox-LDL)100μg/mL诱导24 h,并同时给予含有冠心康低、中、高剂量(1.25、2.5、5μg/mL)的培养基。采用生化检测方法检测小鼠血清TC、TG、LDL-C水平。HE染色、油红O染色法观察小鼠斑块面积及泡沫细胞形成。Western blot测定小鼠及细胞相关蛋白表达。结果:与模型组比较,冠心康降低小鼠血清TC、TG、LDL-C水平(P<0.01),减少小鼠主动脉斑块相对管腔面积(P<0.01),减少ox-LDL诱导RAW264.7细胞形成的脂滴累积,上调SENP1、ABCA1、ABCG1蛋白表达,下调FABP4蛋白表达(P<0.05)。转染si-SENP1慢病毒后,冠心康抑制泡沫细胞形成、下调FABP4蛋白、上调ABCA1、ABCG1蛋白的作用被减弱(P<0.05)。结论:冠心康可通过SENP1分子促进胆固醇逆向转运,抑制泡沫细胞形成,改善脂代谢,从而发挥抗动脉粥样硬化的作用。Objective:To observe the effects of Guanxinkang(GXK)on the reverse cholesterol transport in LDLR-/-mice and RAW264.7 cells.Methods:LDLR-/-mice were randomly divided into control group,model group,Guanxinkang low-,medium-,and high-dose group.Except for the control group,each group was given high-fat feed for 12 weeks.Each group was administered with corresponding normal saline or drugs daily for 12 weeks.RAW264.7 cells or si-SENP1-RAW264.7cells were induced with oxidized low-density lipoprotein(ox-LDL)100μg/mL for 24 h,and at the same time,they were given a medium containing GXK at low-,medium-and high-dose(1.25,2.5,5μg/mL).Biochemical detection methods were used to detect the serum TC,TG,and LDL-C levels of mice.HE and Oil red O staining method were used to observe mice plaque size and the formation of foam cell.Western blot method was used to detect SENP1,FABP4,and reverse cholesterol transport-related proteins of mice and RAW264.7 cells.Results:Compared to the model group,GXK reduced the levels of serum TC,TG,and LDL-C(P<0.01),reduced the area of aortic plaques(P<0.01),reduced the accumulation of lipid droplets induced by ox-LDL in RAW264.7 cells,up-regulated the expression of SENP1,ABCA1,ABCG1 protein,and down-regulated the expression of FABP4 protein(P<0.05).After transfection of si-SENP1 lentivirus,GXK’s effects on inhibiting foam cell formation,downregulating FABP4 protein,and up-regulating ABCA1 and ABCG1 protein were weakened(P<0.05).Conclusion:GXK exerts anti-atherosclerotic effects through SENP1 molecules,promoteing reverse cholesterol transport,inhibiting foam cell formation,and improving lipid metabolism.

关 键 词：SENP1 冠心康 动脉粥样硬化 胆固醇逆向转运 泡沫细胞 益气化痰祛瘀法 

分 类 号：R285.5[医药卫生—中药学]