西罗莫司对大鼠移植心脏组织中整合素ανβ3mRNA表达的影响  

Effect of sirolimus on the expression of integrin αυβ3 mRNA in cardiac allograft in rats

作　　者：胡名松[1] 胡建国[2] 郑宝石[2] 

机构地区：[1]南华大学附属第二医院胸心外科,湖南省衡阳市421001 [2]中南大学湘雅二医院胸心外科

出　　处：《中华器官移植杂志》2011年第3期168-171,共4页Chinese Journal of Organ Transplantation

摘　　要：目的研究大鼠移植心脏冠状血管组织中整合素αυβ3的表达情况及西罗莫司（SRL）对其的影响，探讨SRI。预防移植心脏血管病变的可能机制。方法实验共分4组，每组受者8只，建立大鼠腹腔异位心脏移植模型：（1）同系移植组：供、受者均为Wistar大鼠；（2）同种异体移植环孢素A组（CsA组）：以Wistar大鼠作为供者，SD大鼠作为受者，移植后受者皮下注射CsA10mg·kg^-1·d^-1；（3）同种异体移植SRL组（SRL组）：以Wistar大鼠作为供者，SD大鼠作为受者，移植后受者用SRL1．25mg·kg^-1·d^-1灌胃；（4）对照组：取未经任何处理的Wistar大鼠作为正常对照。移植后60d，取移植心脏组织，行Van Gieson染色观察移植心脏血管病理学改变，采用Mias system 4．1医学图像分析管理系统分析血管狭窄程度，采用逆转录聚合酶链反应法检测整合素αυβ3 mRNA的表达情况，分析整合素αυβ3 mRNA的表达与血管狭窄程度间的关系。结果对照组移植心脏未见血管内膜增厚和管腔狭窄；同系移植组血管内膜稍增厚，但未见管腔狭窄；CsA组血管内膜明显增厚，管腔狭窄，甚至有部分小动脉出现闭塞；SRL组血管内膜增生和血管狭窄程度明显轻于CsA组。对照组、同系移植组、CsA组、SRL组整合素αυβ3 mRNA的相对含量分别为（0．28±0．08）、（0．38±0．05）、（2．51±0．43）、（1．17±0．12），4组间比较，差异均有统计学意义（P〈0．05）。CsA组和SRL组移植心脏组织中整合素αυβ3 mRNA表达量与血管狭窄程度之间均呈正相关（r=0．654，P〈0．01）。结论SRL可降低大鼠同种异体移植心脏组织中整合素αυβ3 mRNA的表达量，SRL预防移植心脏血管病变的作用可能与其抑制整合素αυβ3 mRNA的表达有关。Objective To investigate the effect of sirolimus （SRL） on the expression of integrin αυβ3 mRNA in vascular smooth muscle cells of cardiac allografts in rats, and the possible mechanism of SRL in the prevention of cardiac allograft vasculopathy. Methods Heterotopic heart transplantation models were establishe Hearts from Wistar rats were heterotopically transplanted to SD rats （allograft） or Wistar rats （isograft）. All rats were randomly divided into four groups：SRL group,SRL 1. 25 mg/kg every day, oral intubation after cardiac transplantation; cyclosporine （CsA） group, CsA 10 mg/kg every day, subcutaneous administration; isograft group, no immunosuppressant administration ;control group, normal hearts of Wistar rats. All of the animals were killed at 60 day after transplantation. Angiostenosis degree was analyzed by Mias system 4. 1 after the cardiac tissues were stained with Van Gieson stain. Reverse transcription-polymerase chain reaction （RT-PCR） assay was used to detect the expression of integrin αυβ3 mRNA in cardiac allografts. The relationship between the expression of integrin αυβ3 mRNA and the area of vascular stenosis was analyzed. Results In control group, there was no thickened vascular intima and no vascular stenosis. In allograft group, the thickneSs of vascular intima was slightly increased but no vascular stenosis was detected. In CsA group, the vascular intima was obviously thickened, the lumen was narrowed, and some small arteries had obstruction. In SRL group, vascular intima proliferation and angiostenosis degree were obviously milder than in CsA group. Semiquantitative RT-PCR analysis revealed that the relative expression of integrin αυβ3 mRNA in CsA and SRL groups was increased significantly as compared with control group and isograft group （2.51± 0. 43 or 1.17± 0. 12 vs 0. 28 ±0. 08 or 0. 38 ± 0. 05, P〈0. 01）. The relative expression of integrin αυβ3 mRNA in SRL group was decreased significantly as compared with CsA group （1.17±0. 12 vs 2. 51

关 键 词：西罗莫司 整合素αυβ3 心脏移植 血管病变 

分 类 号：R654.2[医药卫生—外科学]