【作者】 程云鹏；

【导师】 姜一农；

【作者基本信息】 大连医科大学 ， 内科学， 2007， 硕士

【摘要】 目的:罗格列酮可以在多种模型中,通过多种可能机制改善血管内皮细胞功能;而血管内皮细胞是维持正常血管功能的第一道防线,对血流动力学变化非常敏感。切应力是血液流动时血液与血管内皮细胞间产生的摩擦力,其紊乱可能会导致血管内皮细胞功能发生改变,促进动脉粥样硬化的形成。本试验通过研究罗格列酮在雄性BALB/C小鼠血流阻断模型中对结扎侧(低切应力侧)颈总动脉亲环素A、ICAM-1及P-选择素表达的影响,探讨罗格列酮对低切应力导致的血管重构及血管内皮功能的作用。方法:将雄性BALB/C小鼠(12~16周龄,体重30~40g)60只随机分为手术+罗格列酮组(OR组)、手术+安慰剂组(OM组)、假手术+罗格列酮组(SR组)、假手术+安慰剂组(SP组)4组,每组15只。手术组通过在血管分叉处结扎左侧颈总动脉制作血流阻断模型。所有小鼠于术后给与1周时间恢复。术后第8天至第28天,各组通过胃管给药方式(强饲法)分别给予罗格列酮(20mg/kg)或者安慰剂(甲基纤维素,20mg/kg),每日1次。第29天,处死小鼠,按原手术入路分离左侧颈总动脉,并贮藏于-80℃。每组随机取4例标本通过HE染色切片进行血管形态学分析,并使用免疫组织化学染色方法分析亲环素A在蛋白质水平的表达情况;另每组随机取7只小鼠通过实时定量反转录方法检测ICAM-1与P-选择素mRNA的表达。所有数据用均值±标准差表示;统计学分析使用方差分析(ANOVA)SNK法。统计软件为SPSS 13.0 Windows版。p<0.05被视为有统计学意义。结果:1.结扎4周后,手术组与假手术组相比较,左侧颈总动脉发生明显的负性重构,包括血管中层明显增厚,内皮细胞增殖,血管管腔明显狭窄。2.根据免疫组织化学染色结果,亲环素A在各组间的表达无明显差异。3.根据实时定量反转录PCR结果,各组间ICAM-1与P-选择素mRNA的表达无显著性差异(p>0.05)。结论:1.低切应力可导致BALB/C小鼠的颈总动脉发生明显的负性重构,包括血管中层增厚,血管内皮细胞增殖及由此产生的管腔狭窄。2.在本研究中,罗格列酮未能在BALB/C小鼠改善由低切应力导致的颈总动脉负性重构,亦未能改善此模型中的血管内皮功能。更多还原

【Abstract】 Background: Recent studies have shown that rosiglitazone could improve vascular remodeling and endothelial function in some kinds of models by the mechanisms remains unclear. The endothelium can be seen as the first defender to maintain the normal function of vascular, and it is sensitive to the change of haemodynamics. The turbulence of shear stress will change the endothelial function and lead to a facilitation of atheroge- nesis. In the present study, we try to assess the effect of rosiglitazone on the vascular remodeling and the endothelial function in the flow cessation model of male BALB/C mice.Method: 60 male BALB/C mice (12 to 16 weeks’old, 30~40g body weight) were randomized into 4 groups: Operation+Rosiglitazone(OR), Operation+Placebo(O M), Sham-operation+Rosiglitzone(SR) and Sham-operation+Placebo(SM), each group has 15 mice. The blood cessation model was made by ligating the left carotid artery (LCA) at the location of bifurcation with a 6-0 silk. All the mice were given 1 week to recover after the operation. From the 8th day to the 28th day after operation, the 4 groups were administrated with rosiglitazone (20mg/kg) or placebo (methylcellulose, 20mg/kg) by gavage, respectively. On the 29th day, the mice were killed, and the left carotid arteries were isolated and stored at -80℃. HE’s photomicrographs were analyzed for morphology. The proteinic expression of cyclophilin A (CyPA) was observed by immunochemistry. The mRNA’s amount of ICAM-1 and P-selectin were quantitated by real-time quantitative reverse-transcript PCRs. All replicate data are expressed as mean±SEM. Absolute differences amonggroups were compared using a one-way ANOVA (SNK). Statistical signify- cance was achieved when two-tailed p<0.05. Statistical analyses were carried out using SPSS 13.0 (SPSS Inc., Chicago) for windows.Result:1. 4 weeks after operation, comparing with the sham-operated group, the operation groups achieved significant inward remodeling, including media hypertrophy, neointima hyperplasia, and the decreased lumen diameter of the LCA.2. According to the immunochemistry, CyPA has no difference among the 4 groups.3. The quantizations of ICAM-1’s and P-Selectin’s mRNA carried out by the real-time quantitative reverse-transcript PCRs have no difference among the four groups (p>0.05).Conclusion:1. Low shear stress can lead to significant inward remodeling of the LCA in BALB/C mice, including the media hypertrophy, neointima hyperplasia, and decreased vascular lumen linked to these changes.2. In this study, rosiglitazone can’t improve the LCA’s inward remodeling in BALB/C mice with low shear stress, neither the vascular endothelial function in this kind of model.更多还原