CAJ | 학술논문

目的研究大鼠移植心脏冠状血管组织中整合素ανβ3的表达情况及西罗莫司(SRL)对其的影响,探讨SRL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CsA10 mg·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SRL 1.25 mg·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60 d,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ανβ3 mRNA 的表达情况,分析整合素ανβ3mRNA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ανβ3mRNA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ανβ3mRNA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ανβ3 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ανβ3 mRNA的表达有关.
목적 연구대서이식심장관상혈관조직중정합소ανβ3적표체정황급서라막사(SRL)대기적영향,탐토SRL예방이식심장혈관병변적가능궤제.방법 실험공분4조,매조수자8지,건립대서복강이위심장이식모형:(1)동계이식조:공、수자균위Wistar대서;(2)동충이체이식배포소A조(CsA조):이Wistar대서작위공자,SD대서작위수자,이식후수자피하주사CsA10 mg·kg-1·d-1;(3)동충이체이식SRL조(SRL조):이Wistar대서작위공자,SD대서작위수자,이식후수자용SRL 1.25 mg·kg-1·d-1관위;(4)대조조:취미경임하처리적Wistar대서작위정상대조.이식후60 d,취이식심장조직,행Van Gieson염색관찰이식심장혈관병이학개변,채용Mias system 4.1의학도상분석관리계통분석혈관협착정도,채용역전록취합매련반응법검측정합소ανβ3 mRNA 적표체정황,분석정합소ανβ3mRNA적표체여혈관협착정도간적관계.결과 대조조이식심장미견혈관내막증후화관강협착;동계이식조혈관내막초증후,단미견관강협착;CsA조혈관내막명현증후,관강협착,심지유부분소동맥출현폐새;SRL조혈관내막증생화혈관협착정도명현경우CsA조.대조조、동계이식조、CsA조、SRL조정합소ανβ3mRNA적상대함량분별위(0.28±0.08)、(0.38±0.05)、(2.51±0.43)、(1.17±0.12),4조간비교,차이균유통계학의의(P＜0.05).CsA조화SRL조이식심장조직중정합소ανβ3mRNA표체량여혈관협착정도지간균정정상관(r=0.654,P＜0.01).결론 SRL가강저대서동충이체이식심장조직중정합소ανβ3 mRNA적표체량,SRL예방이식심장혈관병변적작용가능여기억제정합소ανβ3 mRNA적표체유관.
Objective To investigate the effect of sirolimus (SRL) on the expression of integrin ανβ3 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 established. 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 10mg/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 ανβ3 mRNA in cardiac allografts. The relationship between the expression of integrin ανβ3 mRNA and the area of vascular stenosis was analyzed. ResultsIn 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 ανβ3 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 ανβ3 mRNA in SRL group was decreased significantly as compared with CsA group (1.17±0.12 vs 2.51±0.43, P＜0.05). A positive correlation was found between vascular stenosis and the expression of integrin ανβ3 mRNA (r = 0. 654, P＜0. 01) in allografts. Conclusion SRL may down-regulate the expression of integrin ανβ3 mRNA in cardiac allografts in rats, which was probably associated with classic cardiac allograft vasculopathy.