吡格列酮对实验性兔主动脉粥样硬化的预防作用被引量：1

Effects of Pioglitazone on Prevention of Atherosclerosis in Experimental Rabbits

下载PDF

导出

摘要目的:探讨预防性应用吡格列酮(Piog)对血脂和动脉粥样硬化(AS)斑块的影响。方法:24只新西兰白兔随机分为四组,I组:正常对照组6只,II组:高胆固醇饮食(Hi-chol)组6只,III组:Hi-chol加高剂量Piog组6只,IV组:Hi-chol加低剂量Piog组6只,喂养8周后处死。于实验终点取兔血清测定血脂;取兔主动脉,观察血管AS斑块及脂质条纹形成情况;免疫组化法测定主动脉血管内皮金属蛋白酶-9(MMP-9)。结果:(1)血脂:Hi-chol成功诱发高脂血症(高TC、TG、LDL-C,HDL-C下降未达显著水平),预防应用高、低剂量Piog明显降低TG,P<0.001。(2)主动脉AS程度:Hi-chol组AS最明显,高、低剂量Piog明显改善主动脉AS情况。(3)主动脉弓血管内壁免疫组化:Hi-chol组、Hi-chol加高低剂量Piog组MMP-9阳性面积比(阳性染色面积/斑块总面积)与正常对照组比较明显升高(P<0.001),高剂量Piog组与单纯Hi-chol组比较,明显降低其表达(P<0.05)。结论:在新西兰兔中,高脂饮食成功诱发高脂血症和动脉粥样硬化,而预防性服用吡格列酮可一定程度上降低TG水平,抑制粥样斑块形成,高剂量吡格列酮降低主动脉粥样斑块内MMP-9表达。 Objective：To observe the preventive effects of pioglitazone on experiental atherosclerotic rabbits. Methods：24 Healthy WHHL（Watanabe Heritable Hyperlipidemic） rabbits were randomly divided into 4 groups（n=6）：I normal control group, II high-cholesterol diet （Hi-chol） group, III hi-chol plus high dose pioglitazone （piog） group, IV Hi-chol plus low dose piog group.All animals were feeding for 8 weeks and sacrificed, taking rabbits blood to measure lipids.Observe rabbit arterial atherosclerosis （AS）. Expression of metalloproteinase-9 （MMP-9） in arterial endothelium were detected by immunohistochemistry.Results：（1）Biochemistry：Hi-chol diet successfully induced hyperlipidemia（high TC,TG,LDL-C） compared with normal diet group （P〈0.001）.High dose piog decreased TG significantly compared with hi-chol diet group （P〈0.001）.（2）Arterial atherosclerosis： The atherosclerosis in hi-chol diet group was serious than control group. High and low dose piog prevented AS formation significantly.（3）Immunohistochemical staining： High cholesterol diet significantly increased MMP-9 expression of arterial wall（P〈0.001）, and hi-chol plus hi-dose piog significantly decreased expression of MMP-9 positive area ratio（P〈0.05）.Conclusions：High cholesterol diet induced hypercholesmia and atherosclerosis in WHHL rabbits. Preventive taking pioglitazone can reduce the elevated TG level, inhibit atherosclerotic plaque formation, decrease the aortic wall MMP-9 expression.

作者张爱娟张爱元王赛季祥武

机构地区山东省潍坊市脑科医院山东省潍坊市人民医院山东省东营市胜利油田中心医院

出处《实用中西医结合临床》 2011年第6期1-3,共3页 Practical Clinical Journal of Integrated Traditional Chinese and Western Medicine

关键词吡格列酮噻唑烷二酮动脉粥样硬化 Pioglitazone Thiazolidinedions Atherosclerosis

分类号 R541.4 [医药卫生—心血管疾病]

引文网络
相关文献

参考文献7

1Minarnikawa J,Tanaka S,Yamauchi M,et al.Potent inhibitory effect of troglitazone on carotid arterial wall thickness in type 2 diabetes[J].J Clin Endocrinol Metab,1998,83:1 818-1 820.
2Adams DH,Tilnev NL, Collins JJJr, et al.Experimental grail arteriosclerosis I.The laws to F 344 allogratt model [J]. Transplantation,1992,53(5):1115-1 119.
3Issemen I,Green S.Activtion of a member of the steroid hormone receptor superfamily by pcroxisome pmliferators [J].Nature,1990, a347:645-650.
4Herz M, Johns D,Reviriego J,et al.A randomized, double blind, placebo controlled, clinical trial of the effects of pioglitazone on glycemic control and dyslipidemia in oral antihyperglycemic medicationnaive patients with type 2 diabetes mellitus [J].Clinical Therapeutics,2003, 25(4):1 074-1 095.
5Harald S,Robert Z, Thomas CW.Effects of pioglitazone function, insulin sensitivity and glucose control in subjects with coronary artery disease and new-onset type 2 diabetes [J].Diabetes Care, 2006,29:1 039-1 045.
6Philippe D,Giulia C.Pcroxisome proliferator-activated receptor activators inhibit thrombin-induced cndothelin-1 production in human vascular endothelial cells by inhibiting the activator protein-1 signaling pathway[J].Circulation Research,1999,85:394-402.
7Shimomi M, Ito T,Tsukada T,et al.Fibmmuscuiar cap composition is important for the stability of established atllen scierotic plaques in mature WHHL rabbits eated with statins[J].Atherosclerosis,1999,142 (2):345-353.