细胞因子信号转导抑制因子3基因转染对小鼠同种异体腹主动脉移植物慢性排斥反应的抑制作用

Anti-chronic rejection effects of adenovirus vector mediated suppressors of cytokine signaling 3 genetransduction on allograft in mouse abdominal aorta transplantation model

目的观察细胞因子信号转导抑制因子3（SOCS3）基因对慢性排斥反应的影响。方法建立小鼠同种异体腹主动脉移植模型，分为对照组、Ad-GFP组和Ad-SOCS3组。分别于术后24h经尾静脉注射100μl无菌磷酸盐缓冲液（PBS）注射液、空白和编码SOCS3基因的腺病毒载体。术后分批获取动脉移植物、脾脏标本，用于组织学、逆转录一聚合酶链反应（RT-PCR）、混合淋巴细胞反应强度（MLR）检测。结果SOCS3基因转染可明显增强移植动脉内SOCS3mRNA表达（P〈0．05）。Ad—SOCS3组移植动脉狭窄率明显降低[（19．62±2．91）％、（35．67±4．72）％和（38．21±3．59）％，P〈0．05]。该组移植动脉内转录信号转导子与激活子3（STAT3）mRNA、干扰素（IFN）-γmRNA、白细胞介素（IL）-6mRNA、血管细胞问黏附分子-1（VCAM-1）mRNA表达明显下调（P〈0．01），MLR明显减弱（P〈0．05）。结论腺病毒载体介导的供体SOCS3基因转染能够抑制移植动脉慢性排斥反应。

Objective To investigate the effect of suppressors of cytokine signaling 3 （ SOCS3 ） on chronic rejection. Methods The mouse model of artery allograft was developed, which were randomly as signed to3 groups： （1）The control group, （2）Ad-SOCS3 group, （3）Ad-GFP group. 24 hours after op- eration, 100 μl sterile phosphate buffer （PBS） injection, 1 x 109 pfu the recombinant adenovirus vector carrying mouse SOCS3 gene and green fluorescent protein （GFP） reported gene were injected by tail vein, respectively. The mouse of each groups were sacrificed in batches. The grafts were used for reverse tran scription-polymerase chain reaction （RT-PCR） and histological detected. And the spleens were used for mixed lymphocyte reaction （MLR）. Results To transfect with Ad-SOCS3 can enhance the SOCS3 mRNA expression in the graft significantly, compared with the control and Ad-GFP groups. The stenosis rate of the graft were （ 19.62 ± 2. 91 ）% in Ad-SOCS3 group, which were significantly down-regulated, compared with （35.67 ± 4. 72 ） % and （ 38.21 ± 3.59 ） % in the control and Ad-GFP groups （ P 〈 0. 05）. The expression of mRNA of signai transducers and activators of transcription 3 （STAT3）, interferon （IFN）-γ, interleukin （IL）-6, VCAM-I were significantly down-regulated in Ad-SOCS3 group, compared with the control and Ad-GFP groups （P 〈 0. 01 ）. The MLR was significantly down-regulated in Ad-SOCS3 group, compared with the control and Ad-GFP groups （ P 〈 0. 05 ）. Conclusion To transfect SOCS3 gene by adenovirus vector can inhibit the chronic rejection of allograft in mice abdominal aorta transplantation model.