低切应力血管重构模型的建立及罗格列酮对其的影响
发布时间：2018-11-27 11:25
【摘要】： 内皮细胞功能障碍是疾病的早期现象,很多疾病如动脉粥样硬化及高血压等与此相关。导致内皮细胞功能障碍的因素有很多,其中剪切力及炎症反应是目前比较热门的研究。PPAR-γ激动剂(噻唑烷二酮类药物thiazolidinedione ,TZD)是近年来发现的一类新型口服胰岛素增敏剂,目前亦有很多关于它抗炎的研究。罗格列酮是噻唑烷二酮类药物的一种,本试验旨在探索一种血管重构模型,并研究罗格列酮对其的作用。目的:探索一种新的血管重构模型,并用罗格列酮加以干预,观察这种药物对血管内皮的影响 方法:用SPF级BALB/C雄性小鼠共50只,随机分成手术+罗格列酮组(OR)、手术+安慰剂组(OM)、假手术+罗格列酮组(SR)、假手术+安慰剂组(SM),颈部正中切口,手术组6.0丝线结扎左侧颈总动脉,假手术组用同样丝线穿过而不结扎,一周恢复时间后,予马来酸罗格列酮(20mg/kg/d)和安慰剂(20mg/kg/d)灌养,三周后取出两侧颈动脉,做免疫组化。免疫组化染色包括过氧化物酶体增殖物活化受体(peroxisome prolife- rater -activated receptor, PPAR-γ)、细胞间粘附分子(int- ercellular adhesion molecule -1,ICAM-1),血管细胞间粘附分子(vascular cell adhesi- on molecule-1,VC AM-1)、P-选择素(P-selectin Ps)、E-选择素(E-selectin Es)。观察上述因子的变化,并采用IPP计算机图象分析系统对染色程度进行光密度量化分析,结果采用SPSS13.0系统进行单因素方差分析。 结果: 1.HE染色:手术组左侧颈总动脉管腔明显狭窄(负性重构),内膜明显增厚,血管中层亦增厚,但外层变薄;但OR组与OM组相比,并无明显不同。假手术组,管腔无明显变化,内膜中膜外膜结构正常。 2.ICAM-1与VCAM-1的免疫组化染色:ICAM-1在血管内皮表达,观察到单独低切应力存在时(OM与SM)ICAM-1表达上调,但灰度分析无明显差异(p0.05);低切应力同时用罗格列酮干预时(OR与OM)ICAM-1表达无明显变化,灰度分析无明显差异(p0.05)。单用罗格列酮干预时(SR与SM)ICAM-1表达无明显变化,灰度分析无明显差异(p0.05)。VCAM-1与ICAM-1结果一致。 3.Ps与Es组免疫组化染色:单独低切应力存在时(OM与SM)Es表达无明显变化,灰度分析无明显差异(p0.05);低切应力同时用罗格列酮干预时(OR与OM)Es表达无明显变化,但灰度分析无明显差异(p0.05)。单用罗格列酮干预时(SR与SM)Es表达无明显变化,灰度分析无明显差异(p0.05)。Ps与Es结果一致。4.单独低切应力存在时(OM与SM)PPAR-γ表达上调,但灰度分析无明显差异(p0.05);低切应力同时用罗格列酮干预时(OR与OM)PPAR-γ表达上调,但灰度分析无明显差异(p0.05)。单用罗格列酮干预时(SR与SM)PPAR-γ表达上调,但灰度分析无差异(p0.05)。 结论: 1.血管切应力改变可以导致慢性血管重构。 2.在罗格列酮干预下血管内皮细胞粘附分子表达未增加。 3.罗格列酮对于低切应力引起的血管重构改善作用不明显。
[Abstract]:Endothelial cell dysfunction is an early stage of the disease, and many diseases such as atherosclerosis and hypertension are associated with it. There are many factors leading to the dysfunction of endothelial cells, and the response of shear and inflammation is a popular study at present. The PPAR-agonist (TZD) is a new type of oral insulin sensitizer, which has been found in recent years. There are also many studies on its anti-inflammatory properties. Rosiglitazone is one of the two drugs of the diketones, and the purpose of this study is to explore a model of vascular remodeling and to study the effect of rosiglitazone on it. Objective: To explore a new model of vascular remodeling and to intervene with rosiglitazone to observe the effect of such a drug on the vascular endothelium. Methods: 50 BALB/ C male mice were randomly divided into operation + rosiglitazone group (OR) and operation. + Placebo group (OM), sham operation + rosiglitazone group (SR), sham operation + placebo group (SM), neck median incision, operation group 6.0 silk ligature left common carotid artery, sham operation group with the same wire without tying After a week of recovery, rosiglitazone maleate (20 mg/ kg/ day) and placebo (20 mg/ kg/ day) were administered and both sides were taken out three weeks later The carotid artery is an immunohistochemical staining. The immunohistochemical staining includes peroxisome proliferator-activated receptor (PPAR-1), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule (ICAM-1), vascular cell adhesion molecule (vascular cell adhesion molecule-1, VC AM-1), and P-selectin (P-se). lectin Ps), E-selectin (E-se) The change of the above factors was observed, and the optical density was quantified by the image analysis system of the IPP. The result was that the SPSS13.0 system was used. Make a single The results were as follows: 1. HE staining: the left common carotid artery lumen of the operation group was obviously narrow (negative reconstruction), the intima was obviously thickened, and the blood vessels the middle layer is also thickened, but the outer layer is thinned; however, the OR group is compared with the OM group and There was no significant difference in the expression of ICAM-1 and VCAM-1. The expression of ICAM-1 was up-regulated in the presence of low-shear stress (OM and SM), but there was no significant difference in the gray-scale analysis (p0).. 05); low shear stress with rosiglitazone There was no significant difference in the expression of ICAM-1 in the pre-time (OR and OM). There was no significant difference in the gray-scale analysis (p0.05). The expression of ICAM-1 in the single-use rosiglitazone (SR and SM) did not change. There was no significant difference in gray-scale analysis (p0.05). VCAM-1 was consistent with the results of ICAM-1. At the same time, there was no significant difference in the expression of (OR and OM) Es in the case of low shear stress, but there was no significant difference in the gray-scale analysis (p0.05). The single-use rosiglitazone There was no significant difference in the expression of (SR and SM) Es, and there was no significant difference in gray-scale analysis (p0.05). Ps were consistent with the results of Es. 4. The expression of PPAR-1 was up-regulated in the presence of low-shear stress alone (OM and SM), but there was no significant difference in the gray-scale analysis (p0.05). While the low shear stress was up-regulated with rosiglitazone (OR and OM), the expression of PPAR-1 was up-regulated, but there was no significant difference in the gray-scale analysis. p0. 05). Single use of rosiglitazone (SR and SM) The expression of PPAR-1 was up-regulated, but there was no difference in the gray level (p0.05). Conclusion: 1. Blood
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R-331;R965
本文编号：2360573
[Abstract]:Endothelial cell dysfunction is an early stage of the disease, and many diseases such as atherosclerosis and hypertension are associated with it. There are many factors leading to the dysfunction of endothelial cells, and the response of shear and inflammation is a popular study at present. The PPAR-agonist (TZD) is a new type of oral insulin sensitizer, which has been found in recent years. There are also many studies on its anti-inflammatory properties. Rosiglitazone is one of the two drugs of the diketones, and the purpose of this study is to explore a model of vascular remodeling and to study the effect of rosiglitazone on it. Objective: To explore a new model of vascular remodeling and to intervene with rosiglitazone to observe the effect of such a drug on the vascular endothelium. Methods: 50 BALB/ C male mice were randomly divided into operation + rosiglitazone group (OR) and operation. + Placebo group (OM), sham operation + rosiglitazone group (SR), sham operation + placebo group (SM), neck median incision, operation group 6.0 silk ligature left common carotid artery, sham operation group with the same wire without tying After a week of recovery, rosiglitazone maleate (20 mg/ kg/ day) and placebo (20 mg/ kg/ day) were administered and both sides were taken out three weeks later The carotid artery is an immunohistochemical staining. The immunohistochemical staining includes peroxisome proliferator-activated receptor (PPAR-1), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule (ICAM-1), vascular cell adhesion molecule (vascular cell adhesion molecule-1, VC AM-1), and P-selectin (P-se). lectin Ps), E-selectin (E-se) The change of the above factors was observed, and the optical density was quantified by the image analysis system of the IPP. The result was that the SPSS13.0 system was used. Make a single The results were as follows: 1. HE staining: the left common carotid artery lumen of the operation group was obviously narrow (negative reconstruction), the intima was obviously thickened, and the blood vessels the middle layer is also thickened, but the outer layer is thinned; however, the OR group is compared with the OM group and There was no significant difference in the expression of ICAM-1 and VCAM-1. The expression of ICAM-1 was up-regulated in the presence of low-shear stress (OM and SM), but there was no significant difference in the gray-scale analysis (p0).. 05); low shear stress with rosiglitazone There was no significant difference in the expression of ICAM-1 in the pre-time (OR and OM). There was no significant difference in the gray-scale analysis (p0.05). The expression of ICAM-1 in the single-use rosiglitazone (SR and SM) did not change. There was no significant difference in gray-scale analysis (p0.05). VCAM-1 was consistent with the results of ICAM-1. At the same time, there was no significant difference in the expression of (OR and OM) Es in the case of low shear stress, but there was no significant difference in the gray-scale analysis (p0.05). The single-use rosiglitazone There was no significant difference in the expression of (SR and SM) Es, and there was no significant difference in gray-scale analysis (p0.05). Ps were consistent with the results of Es. 4. The expression of PPAR-1 was up-regulated in the presence of low-shear stress alone (OM and SM), but there was no significant difference in the gray-scale analysis (p0.05). While the low shear stress was up-regulated with rosiglitazone (OR and OM), the expression of PPAR-1 was up-regulated, but there was no significant difference in the gray-scale analysis. p0. 05). Single use of rosiglitazone (SR and SM) The expression of PPAR-1 was up-regulated, but there was no difference in the gray level (p0.05). Conclusion: 1. Blood
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R-331;R965
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相关期刊论文 前3条
1 张旭静;黄久仪;王桂清;;血流动力学与动脉粥样硬化[J];国际脑血管病杂志;2006年03期
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3 罗谋伦,郭欲晓,胡映辉,林志彬;罗格列酮的胰岛素增敏作用和胰岛素抵抗改善作用[J];中国药理学通报;2000年04期
，本文编号：2360573
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