低切應(yīng)力血管重構(gòu)模型的建立及羅格列酮對其的影響
發(fā)布時(shí)間：2018-11-27 11:25
【摘要】： 內(nèi)皮細(xì)胞功能障礙是疾病的早期現(xiàn)象,很多疾病如動(dòng)脈粥樣硬化及高血壓等與此相關(guān)。導(dǎo)致內(nèi)皮細(xì)胞功能障礙的因素有很多,其中剪切力及炎癥反應(yīng)是目前比較熱門的研究。PPAR-γ激動(dòng)劑(噻唑烷二酮類藥物thiazolidinedione ,TZD)是近年來發(fā)現(xiàn)的一類新型口服胰島素增敏劑,目前亦有很多關(guān)于它抗炎的研究。羅格列酮是噻唑烷二酮類藥物的一種,本試驗(yàn)旨在探索一種血管重構(gòu)模型,并研究羅格列酮對其的作用。目的:探索一種新的血管重構(gòu)模型,并用羅格列酮加以干預(yù),觀察這種藥物對血管內(nèi)皮的影響 方法:用SPF級BALB/C雄性小鼠共50只,隨機(jī)分成手術(shù)+羅格列酮組(OR)、手術(shù)+安慰劑組(OM)、假手術(shù)+羅格列酮組(SR)、假手術(shù)+安慰劑組(SM),頸部正中切口,手術(shù)組6.0絲線結(jié)扎左側(cè)頸總動(dòng)脈,假手術(shù)組用同樣絲線穿過而不結(jié)扎,一周恢復(fù)時(shí)間后,予馬來酸羅格列酮(20mg/kg/d)和安慰劑(20mg/kg/d)灌養(yǎng),三周后取出兩側(cè)頸動(dòng)脈,做免疫組化。免疫組化染色包括過氧化物酶體增殖物活化受體(peroxisome prolife- rater -activated receptor, PPAR-γ)、細(xì)胞間粘附分子(int- ercellular adhesion molecule -1,ICAM-1),血管細(xì)胞間粘附分子(vascular cell adhesi- on molecule-1,VC AM-1)、P-選擇素(P-selectin Ps)、E-選擇素(E-selectin Es)。觀察上述因子的變化,并采用IPP計(jì)算機(jī)圖象分析系統(tǒng)對染色程度進(jìn)行光密度量化分析,結(jié)果采用SPSS13.0系統(tǒng)進(jìn)行單因素方差分析。 結(jié)果: 1.HE染色:手術(shù)組左側(cè)頸總動(dòng)脈管腔明顯狹窄(負(fù)性重構(gòu)),內(nèi)膜明顯增厚,血管中層亦增厚,但外層變薄;但OR組與OM組相比,并無明顯不同。假手術(shù)組,管腔無明顯變化,內(nèi)膜中膜外膜結(jié)構(gòu)正常。 2.ICAM-1與VCAM-1的免疫組化染色:ICAM-1在血管內(nèi)皮表達(dá),觀察到單獨(dú)低切應(yīng)力存在時(shí)(OM與SM)ICAM-1表達(dá)上調(diào),但灰度分析無明顯差異(p0.05);低切應(yīng)力同時(shí)用羅格列酮干預(yù)時(shí)(OR與OM)ICAM-1表達(dá)無明顯變化,灰度分析無明顯差異(p0.05)。單用羅格列酮干預(yù)時(shí)(SR與SM)ICAM-1表達(dá)無明顯變化,灰度分析無明顯差異(p0.05)。VCAM-1與ICAM-1結(jié)果一致。 3.Ps與Es組免疫組化染色:單獨(dú)低切應(yīng)力存在時(shí)(OM與SM)Es表達(dá)無明顯變化,灰度分析無明顯差異(p0.05);低切應(yīng)力同時(shí)用羅格列酮干預(yù)時(shí)(OR與OM)Es表達(dá)無明顯變化,但灰度分析無明顯差異(p0.05)。單用羅格列酮干預(yù)時(shí)(SR與SM)Es表達(dá)無明顯變化,灰度分析無明顯差異(p0.05)。Ps與Es結(jié)果一致。4.單獨(dú)低切應(yīng)力存在時(shí)(OM與SM)PPAR-γ表達(dá)上調(diào),但灰度分析無明顯差異(p0.05);低切應(yīng)力同時(shí)用羅格列酮干預(yù)時(shí)(OR與OM)PPAR-γ表達(dá)上調(diào),但灰度分析無明顯差異(p0.05)。單用羅格列酮干預(yù)時(shí)(SR與SM)PPAR-γ表達(dá)上調(diào),但灰度分析無差異(p0.05)。 結(jié)論: 1.血管切應(yīng)力改變可以導(dǎo)致慢性血管重構(gòu)。 2.在羅格列酮干預(yù)下血管內(nèi)皮細(xì)胞粘附分子表達(dá)未增加。 3.羅格列酮對于低切應(yīng)力引起的血管重構(gòu)改善作用不明顯。
[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
【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2007
【分類號】：R-331;R965
本文編號：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
【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2007
【分類號】：R-331;R965
【參考文獻(xiàn)】
相關(guān)期刊論文 前3條
1 張旭靜;黃久儀;王桂清;;血流動(dòng)力學(xué)與動(dòng)脈粥樣硬化[J];國際腦血管病雜志;2006年03期
2 陳友琴,陳槐卿,劉肖珩,雷松,毛詠秋,張文勝;流體切應(yīng)力對內(nèi)皮細(xì)胞粘附分子表達(dá)的影響[J];生物醫(yī)學(xué)工程學(xué)雜志;2001年02期
3 羅謀倫,郭欲曉,胡映輝,林志彬;羅格列酮的胰島素增敏作用和胰島素抵抗改善作用[J];中國藥理學(xué)通報(bào);2000年04期
，本文編號：2360573
本文鏈接：http://sikaile.net/yixuelunwen/binglixuelunwen/2360573.html
最近更新
教材專著
