金丝桃苷通过NOS/NO系统调控血管内皮影响动脉粥样硬化进程的实验研究  

Experimental study of hyperoside on process of atherosclerosis by regulating vascular endothelium via NOS/NO system

作　　者：刘驰 闵冬雨[2] 朱竟赫 袁宇 关晓娇 胡丽萍[1] LIU Chi;MIN Dongyu;ZHU Jinghe;YUAN Yu;GUAN Xiaojiao;HU Liping(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China;The First Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,China;Liaoning Iinstitute of Traditional Chinese Medicine,Shenyang 110034,China)

机构地区：[1]辽宁中医药大学,辽宁沈阳110847 [2]辽宁中医药大学附属医院,辽宁沈阳110032 [3]辽宁省中医药研究院,辽宁沈阳110034

出　　处：《药物评价研究》2021年第5期971-977,共7页Drug Evaluation Research

基　　金：辽宁省自然科学基金面上项目(2015010708)。

摘　　要：目的探讨金丝桃苷通过一氧化氮合酶(NOS)/一氧化氮(NO)系统调控血管内皮影响动脉粥样硬化进程。方法采用高脂饲料喂养ApoE^(-/-)小鼠复制动脉粥样硬化模型。在造模的同时给予金丝桃苷(200 mg/kg)和辛伐他汀(阳性对照,5.2 mg/kg)进行干预,每天给药2次,连续12周,每周称小鼠体质量;全血项分析仪检测小鼠血清中总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)的含量;ELISA法检测小鼠血清中丙二醛(MDA)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、NO和内皮型一氧化氮合酶(eNOS)的含量;HE染色法和油红O染色法观察小鼠胸主动脉病理学变化情况和脂质沉积状况;Western blotting检测小鼠胸主动脉中聚二磷酸腺苷核糖聚合酶1(PARP1)、精氨酸酶Ⅱ(ARG2)、eNOS和诱导型一氧化氮合酶(iNOS)蛋白的表达。结果与模型组比较,金丝桃苷显著抑制小鼠体质量增长(P<0.05、0.01);显著降低小鼠血清中LDL-C、MDA和IL-6的水平(P<0.05、0.01),显著升高NO和eNOS的水平(P<0.05、0.01);显著减小小鼠主动脉管腔内斑块面积(P<0.05、0.01)并改善脂质沉积状况;显著下调小鼠主动脉组织PARP1、ARG2、iNOS的表达,并上调eNOS的表达(P<0.01)。结论金丝桃苷可以减缓动脉粥样硬化的病理进程,可能是通过降低LDL-C水平、影响NOS活性、调节NO的合成,改善血管内皮功能实现的。Objective To investigate hyperoside through the nitric oxide synthase(NOS)/nitrogen oxide(NO)system regulate the vascular endothelium and affect the atherosclerosis process.Methods ApoE^(-/-)mice were fed with high-fat diet to reproduce the atherosclerosis model.Drug intervention was given at the same time as the model for 12 weeks.The mouse growth was Monitored.The contents of total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C)in serum were detected by an automatic biochemical analyzer.The levels of malondialdehyde(MDA),interleukin-6(IL-6),NO,tumor necrosis factor-α(TNF-α)and endothelial nitric oxide synthase(eNOS)were measured by ELISA.HE staining and Oil red O staining were used to observe the pathological changes and the lipid deposition in the thoracic aorta of mice.Western blotting was used to detect the expressions of poly ADP-ribose polymerase 1(PARP1),arginase II(ARG2),eNOS and inducible nitric oxide synthase(iNOS)proteins in aorta.Results Compared with model group,hyperoside significantly inhibited the weight gain of mice(P<0.05 or 0.01).Hyperoside significantly reduced the levels of LDL-C,MDA and IL-6 in mouse serum,and increase the levels of NO and eNOS(P<0.05 or 0.01).Hyperoside could reduce the plaque area(P<0.05 or 0.01)and improve the lipid deposition in rat aortic lumen.Hyperoside significantly down-regulated the expression of PARP1,ARG2,and iNOS in mouse aortic tissue,and up-regulated the expression of eNOS(P<0.05).Conclusion Hyperoside can slow down the pathological process of atherosclerosis.It may be achieved by decreasing LDL-C level,affecting NOS activity,regulating NO synthesis and improving vascular endothelial function.

关 键 词：金丝桃苷 动脉粥样硬化 血管内皮 一氧化氮合酶 NO 聚二磷酸腺苷核糖聚合酶1 精氨酸酶Ⅱ 

分 类 号：R285.5[医药卫生—中药学]