地奥心血康联合辛伐他汀对动脉粥样硬化小鼠的影响及机制研究  

Study on the Effect and Mechanism of Di’ ao Xinxuekang Combined with Simvastatin on Atherosclero⁃ sis Mice

作　　者：李薇[1] 李璐瑶 瞿礼萍[1] 刘宏林 赖梦婷 王姿倩 邹文俊[1] LI Wei;LI Luyao;QU Liping;LIU Honglin;LAI Mengting;WANG Ziqian;ZOU Wenjun(State Key Laboratory of Southwestern Chinese Medicine Resources,Chengdu University of Traditional Chinese Medicine,Chengdu 611137 Sichuan,China)

机构地区：[1]成都中医药大学/西南特色中药资源国家重点实验室,四川成都611137

出　　处：《中药新药与临床药理》2024年第6期798-804,共7页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金青年科学基金项目(82004175)。

摘　　要：目的探讨地奥心血康(以下简称心血康)联合辛伐他汀对动脉粥样硬化(AS)小鼠的影响及机制。方法将8只C57BL/6J小鼠作为对照组,将32只ApoE^(-/-)小鼠随机分为模型组、心血康组(160 mg·kg^(-1))、辛伐他汀组(1.3 mg·kg^(-1))及联合治疗组(心血康160 mg·kg^(-1)+辛伐他汀1.3 mg·kg^(-1)),每组8只。对照组给予常规饲料喂养,其余4组均给予高脂饲料喂养。同时,各给药组均按照上述剂量灌胃给药,灌胃体积为10 mL·kg^(-1),每天1次,持续18周。给药结束后,检测血清总胆固醇(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)水平;采用油红O染色法观察小鼠主动脉斑块形成及肝脏脂质聚集情况;ELISA法检测血清前蛋白转化酶枯草溶菌素9(PCSK9)水平;qRT-PCR及Western Blot法检测肝脏组织LDLR、HNF1α、SREBP2 mRNA及蛋白表达水平。结果(1)与对照组比较,模型组小鼠的血清TC、TG、LDL-C水平显著升高(P<0.01),HDL-C水平显著降低(P<0.01);主动脉根斑块面积百分比、主动脉全体斑块面积百分比、肝脏脂滴面积百分比均显著升高(P<0.01);肝脏组织中LDLR mRNA及蛋白表达水平显著降低(P<0.01),血清PCSK9水平显著升高(P<0.01);肝脏组织中HNF1α、SREBP2 mRNA及蛋白表达水平均明显升高(P<0.05,P<0.01)。(2)与模型组比较,心血康组及联合治疗组小鼠的血清TC、TG、LDL-C水平明显降低(P<0.05,P<0.01),HDL-C水平明显升高(P<0.05);辛伐他汀组小鼠血清LDL-C水平显著降低(P<0.01);心血康组及联合治疗组小鼠的主动脉根斑块面积百分比、主动脉全体斑块面积百分比明显降低(P<0.05,P<0.01),各给药组小鼠的肝脏脂滴面积百分比均显著降低(P<0.01);心血康组及联合治疗组小鼠肝脏组织中LDLR蛋白表达水平明显升高(P<0.05),血清PCSK9水平明显降低(P<0.05,P<0.01),肝脏组织中HNF1α、SREBP2 mRNA及蛋白表达水平均明显降低(P<0.05,P<0.01)。(3)与辛伐他汀组比�Objective To investigate the effect and mechanism of Di’ao Xinxuekang(hereinafter referred to as Xinxuekang)combined with Simvastatin on atherosclerosis(AS)mice.Methods Eight C57BL/6J mice were used as control group,and 32 ApoE^(-/-)mice were randomly divided into model group,Xinxuekang group(160 mg·kg^(-1)),Simvastatin group(1.3 mg·kg^(-1))and combined treatment group(Xinxuekang 160 mg·kg^(-1)+Simvastatin 1.3 mg·kg^(-1)),with eight mice in each group.The control group was fed with conventional diet,and the other four groups were fed with high-fat diet.At the same time,each administration group was given intragastric administration according to the above dose,and the volume of intragastric administration was 10 mL·kg^(-1),once a day for 18 weeks.After administration,the levels of serum total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C)and high density lipoprotein cholesterol(HDL-C)were detected.Oil red O staining was used to observe the formation of aortic plaque and liver lipid accumulation in mice.Serum PCSK9 level was detected by ELISA.The mRNA and protein expression levels of LDLR,HNF1αand SREBP2 in liver tissues were detected by qRT-PCR and Western Blot.Results(1)Compared with the control group,the levels of serum TC,TG and LDL-C in the model group were significantly increased(P<0.01),and the level of HDL-C was significantly decreased(P<0.01).The percentage of aortic root plaque area,the percentage of total aortic plaque area and the percentage of liver lipid droplet area were significantly increased(P<0.01).The mRNA and protein expression levels of LDLR in liver tissue were significantly decreased(P<0.01),and the serum PCSK9 level was significantly increased(P<0.01).The mRNA and protein expression levels of HNF1αand SREBP2 in liver tissues were significantly increased(P<0.05,P<0.01).(2)Compared with the model group,the levels of serum TC,TG and LDL-C in the Xinxuekang group and the combined treatment group were significantly decreased(P<0.05,P<0.01),and the level of H

关 键 词：地奥心血康 辛伐他汀 联合用药 动脉粥样硬化 协同增效 PCSK9/LDLR信号途径 小鼠 

分 类 号：R285.5[医药卫生—中药学]