罗格列酮对动脉粥样硬化的影响及其机制研究  

Effect of rosiglitazone on atherosclerosis and its mechanism

作　　者：王梓良[1] 钟一鸣[1] 王小萍[1] 周爱琴[1] 曾石秀[1] WANG Zi-liang;ZHONG Yi-ming;WANG Xiao-ping;ZHOU Ai-qin;ZENG Shi-xiu(Department of Cardiology,The First Affiliated Hospital of Gannan Medical University,Ganzhou,Jiangxi 341000)

机构地区：[1]赣南医学院第一附属医院心内科,江西赣州341000

出　　处：《赣南医学院学报》2020年第2期145-151,共7页JOURNAL OF GANNAN MEDICAL UNIVERSITY

摘　　要：目的:探讨罗格列酮对动脉粥样硬化的影响及其可能的机制。方法:50只SD大鼠,大鼠均为8周龄,雄性,体重240~260 g,随机分为5组,每组各10只,Ⅰ组:正常对照组;Ⅱ组:正常对照组+低剂量罗格列酮(3 mg·kg^-1·d^-1);Ⅲ组:模型组;Ⅳ组:模型组+低剂量罗格列酮(3 mg·kg^-1·d^-1);Ⅴ组:模型组+高剂量罗格列酮(9 mg·kg^-1·d^-1)。Ⅲ、Ⅳ、Ⅴ组大鼠连续3天腹腔注射维生素D 360万IU·kg^-1·d^-1,并给予高脂饲料饲养,Ⅰ和Ⅱ组给予等体积生理盐水腹腔注射,普通饲料饲养。从第4周后开始,Ⅱ、Ⅳ、Ⅴ组开始用上述两种剂量罗格列酮治疗8周。于第12周末处死动物并留取标本。测定每组血脂变化,并观察每组主动脉病理形态学改变,检测过氧化物酶体增殖激活受体γ(peroxisome proliferator-activated receptorγ,PPARγ)、α平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)、增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)、血小板源生长因子-B(platelet-derived growth factor-B,PDGF-B)蛋白表达。结果:(1)大鼠通过高脂喂养后血脂水平明显升高(P<0.01),罗格列酮治疗组与模型组相比较,甘油三酯(TG)降低、高密度脂蛋白胆固醇(HDL-C)升高(P<0.01)。(2)罗格列酮治疗组与模型组相比较,动脉粥样硬化病变明显减轻,斑块面积明显减少(P<0.01)。(3)模型组与对照组相比较,PPARγmRNA及蛋白表达显著升高(P<0.01);而罗格列酮治疗组与模型组比较,PPARγmRNA及蛋白水平明显下降(P<0.01),但仍明显高于对照组(P<0.01)。(4)模型组与对照组比较,PDGF-B mRNA及蛋白、PCNA蛋白表达显著增加(P<0.01),而罗格列酮治疗组与模型组比较,上述指标显著降低(P<0.01),但仍较正常对照组明显升高(P<0.01)。(5)模型组及罗格列酮治疗组与对照组相比较,α-SMA蛋白水平均显著下降(P<0.01),但罗格列酮治疗组与模型组比较,α-SMA蛋白水平表达显著升高(P<0.01)。(6)PCNA表达与PDGF-B表达呈显著正相�Objective:To investigate the effect of rosiglitazone on atherosclerosis and its possible mechanism.Methods:50 SD rats were randomly divided into 5 groups,rats were 8 weeks old,male,weighing between 240 g and 260 g,10 in each group.GroupⅠ:normal control group,groupⅡ:normal control group+low dose rosiglitazone(3 mg·kg^-1·d^-1),groupⅢ:model group,group IV:model group+low dose rosiglitazone(3 mg·kg^-1·d^-1),group V:model group+high dose rosiglitazone(9 mg·kg^-1·d^-1).Rats in groupsⅢ,ⅣandⅤwere intraperitoneally injected with vitamin D 3600,000 IU·kg^-1·d^-1 for 3 consecutive days,and were fed with high-fat diet.GroupsⅠandⅡwere given an equal volume of normal saline for intraperitoneal injection and fed with normal diet.Starting from week 4,groupsⅡ,Ⅳ,andⅤbegan treatment with the above two doses of rosiglitazone for 8 weeks.Animals were sacrificed at the end of the 12th week and specimens were taken.The changes of blood lipids in each group were measured,and the pathological changes of aorta in each group were observed.Peroxisome proliferator-activated receptorγ(PPARγ),α-smooth muscle actin(α-SMA),proliferating cell nuclear antigen(PCNA),Platelet-derived growth factor-B(PDGF-B)protein expression.Results:(1)The blood lipid level of rats was significantly increased after high-fat feeding(P<0.01).Compared with the model group,the TG decreased and HDL-C increased in the rosiglitazone treatment group(P<0.01).(2)Compared with the model group,the rosiglitazone treatment group showed a significant reduction in atherosclerotic lesions and a significant reduction in plaque area(P<0.01).(3)Compared with the control group,the expression of PPARγmRNA and protein was significantly increased in the model group(P<0.01).However,the PPARγmRNA and protein levels were significantly decreased in the rosiglitazone treatment group compared with the model group(P<0.01).However,it was still significantly higher than the control group(P<0.01).(4)Compared with the control group,the expression of PDGF-B mRNA,pro

关 键 词：罗格列酮 动脉粥样硬化 增殖细胞核抗原 Α平滑肌肌动蛋白 过氧化酶体增殖物激活型受体γ 血小板源性生长因子-B 

分 类 号：R285[医药卫生—中药学]