【作者】 陈雍；

【导师】 金元哲；

【作者基本信息】 中国医科大学 ， 内科学， 2010， 硕士

【摘要】 前言尾加压素Ⅱ(urotensinⅡ, UTⅡ)最早从鱼尾部下垂体中提取出的神经肽,是目前所知的体内最强的缩血管活性肽。其受体广泛分布于哺乳动物的心脏、肾脏、神经组织、血管平滑肌组织、甚至于动脉粥样硬化斑块中。UTⅡ在动脉粥样硬化中发生发展中扮演中重要角色。本实验中我们通过复制家兔动脉粥样硬化模型,观察从正常家兔直至致病过程中尾加压素动态改变,及其与血脂变化,炎症因子含量的相关性,探讨尾加压素在致动脉粥样硬化中的重要意义。目的研究动脉粥样硬化模型中UTⅡ血浆含量的动态变化,及其与血脂蛋白炎症因子的相关性分析。材料方法1.材料健康日本大耳白家兔40只,4月龄,雌雄不限,购自沈阳市药科大学,合格证号：SCXK(辽)2009-0002,体重2.0-2.5Kg。2.高脂饲料的配制基础饲料中加入胆固醇(国药化学试剂有限公司,上海产,分析纯)、猪油(市售)、蛋黄粉(市售),三种成分按0.6%,3.3%,8.3%配比制成,称为高脂饮食。3.实验动物处理随机将家兔分为2组,对照组20只,实验组20只。单笼饲养,自由摄取饮水。实验组家兔饲喂高脂饲料,对照组继续饲喂基础兔饲料。每日每只家兔进食150g,实验组保证每日每只家兔进食胆固醇1.0g,猪油5.0g,蛋黄粉12.5g。总共喂养12周。4.生化项目检测于实验的0周、3周、6周、9周、12周抽血留取血浆标本,测定血清TC、HDLC、LDLC水平；应用酶联免疫法测定UTⅡ、IL-6水平。同时进行UTⅡ与血脂蛋白、炎症因子相关性分析。5.统计学分析应用SPSS13.0统计学软件,组间比较采用方差分析。实验结果1.家兔体重变化,血脂含量变化喂养12周后家兔体重均增加,但两组间无差异(P>0.05)。实验组家兔血脂水平总体呈升高趋势。6周时,与对照组相比,实验组家兔血脂水平均升高,差别有统计学意义(P<0.05),12周实验组家兔与6周实验组家兔比较,TC和LDLC差别显著(P均<0.01)。2.家兔血浆炎症因子UTⅡ及IL-6含量的变化高脂饮食喂养的家兔在3周时血浆中UTⅡ含量开始下降,第12周较对照组及第6周可见其含量明显减少,有显著差异(P均<0.01)。炎症因子IL-6含量在6周时开始升高,但差别无统计学意义(P>0.05),9周及12周可见炎症因子含量明显增高,与对照组及6周实验组有显著差别(P均<0.01)3.UTⅡ与TC、IL-6相关性分析家兔动脉粥样硬化模型中UTⅡ与TC血清中含量呈明显负相关, r=-0.99,P=0.01,直线回归方程Y=0.211-0.003X。UTⅡ与IL-6血清中含量呈明显负相关,r=-0.95,P=0.04,直线回归方程Y=0.513-0.002X。结论UTⅡ参与了家兔动脉粥样硬化形成过程,并且其血清中含逐渐降低。其与血脂水平,炎症因子IL-6血清水平呈明显负相关。在动脉粥样硬化形成过程中血脂水平明显升高,而以总胆固醇升高最为显著。炎症反应贯穿于动脉粥样硬化形成的始终,并在其中与UTⅡ相互作用,最终导致动脉粥样硬化形成。更多还原

【Abstract】 IntroductionUrotensinⅡ(UTⅡ)was konwn to be the most vasoconstriction peptide,which widely distributed in the tissue of heart、kidney、vessel soomth muscle、even artherosclerosis plaque.It palys a key role in the mechanism of artherosclerosis plaque formation.In our study,the model of artherosclerosis model was made with rabbits,we investigate plasma change of urotensinⅡ,the relationgship between IL-6,TC.Make clear the important effect of urotensinⅡin the mechanism of artherosclerosis.PurposeThis study designed to investigate the difference of the plasma level of urotensinⅡthe relationship between urotensinⅡ、IL-6and TC.Material and methods1.material40 healty rabbits weighing 2.0-2.5kg,were obtained from department of animals,shenyang pharmaceutical university.2.preparation of high-fat diet The basic stoyer consist 0.6%cholest,3.3% lard,8.3% egg yolk to make the high-fat diet.3.Animal treatmentRabbits were randomly divided into two groups,the control group and the artherosclerosis group,each group contain 20 rabbits. The control group keep feding with basic rabbit stoyer, artherosclerosis group,fedding with high-fat diet.every day,each artherosclerosis group rabbit eats 150g stoyer with contain choles t1.0g, lard 5.0g, egg yolk 12.5g.the study continue 12 weeks.4.detection of the biochemical projectsWe detected the rsbbits serum total choletrol,triglyceride,low density lipoprotein-cholesterol, high density lipoprotein-cholesterol. urotensinll and IL-6 were determined by elisa method.5.statistical analysisThe result were processed by SPSS13.0 software.differences between the group were analyzed by Analysis of Variance(ANOVA).Results1.Difference of body weight and serom lipid of rabbits in each groupThe difference of weight between rach has no significant sense. (P>0.05).serum lipid especially TC and LDLC had predominance higher when compare to control group and artherosclerosis grou.12weeks experimental group make obvious higher than 6weeks experimental group. (P<0.01)。2.Difference of plasma UTⅡand IL-6 in each groupThe plasma level of UTⅡin high-fat diet group goes down at 3weeks.12weeks level make big difference between control group and 6weeks group, (P< 0.01).Compared 6weeks and control group level of IL-6,the 12week high-fat diet group increased significant, (P<0.01)3.the relationship between UTⅡ、L-6 and TCIn our study we can see negative relation between UTⅡand TC, regression equation Y=0.211-0.003X r=-0.99, P=0.01. there was also negative relation between UTⅡand IL-6 regression equation Y=0.513-0.002X,r=-0.95, P=0.04。 conclusionUTⅡparticipate the foremation of artherosclerosis,goes decrese of plasma level. UTⅡmake obviouse negative relation between serum lipid and IL-6.There was significant upgrade of serum lipid level, especially TC.The inflammation reaction penetrate the formation of artherosclerosis,they interact tightly,make key role in artherosclerosis formation.更多还原