| RNA干扰T细胞mTOR表达后诱导T细胞分化对小肠移植耐受的影响 |
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| 引用本文： | 胡野,楼宏强,何忠平,王岚,何旭英.RNA干扰T细胞mTOR表达后诱导T细胞分化对小肠移植耐受的影响[J].金华职业技术学院学报,2014,14(6):74-79. |
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| 作者姓名： | 胡野 楼宏强 何忠平 王岚 何旭英 |
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| 作者单位： | 1. 金华职业技术学院,浙江金华,321007
2. 金华市食品药品检验所,浙江金华,321000 |
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| 基金项目： | 浙江省实验动物科技计划资助项目 |
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| 摘 要： | 目的:探讨RNA干扰T细胞mTOR表达后诱导T细胞分化对小肠移植免疫耐受的影响。方法:通过shRNA干扰T细胞mTOR表达后,诱导T细胞向Foxp3+Tregs细胞分化。对60只雄性SD大鼠施行30次异位节段小肠移植,随机分为A组(mTOR-shRNA转染组)、B组(mTOR抑制剂RAD001干预)和C组(移植对照组、注射生理盐水)。观察小肠移植后受体大鼠的体重变化、生存时间及移植小肠病理切片评估排斥反应程度。结果:构建的mTOR-shRNA质粒表达载体在体外能有效地抑制大鼠骨髓细胞mTOR基因mRNA和蛋白的表达。RNA干扰大鼠T细胞mTOR基因可调节T细胞的定向分化,Tregs细胞增多,而Th17细胞分化减少。抑制mTOR基因可诱导大鼠异位小肠移植的免疫耐受,减轻受体抗移植物的排斥反应,显著延长移植物的存活时间。结论:RNA干扰T细胞mTOR表达后诱导T细胞分化对小肠移植耐受的研究为mTOR抑制剂(RAD001)在移植后的临床应用提供理论和实验依据。
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| 关 键 词： | 免疫耐受 RNA干扰 T淋巴细胞 mTOR基因 小肠移植 |
The Effect of T Cell Differentiation induced by mTOR Expression Via RNA Interference on the Immune Tolerance of Small Bowel Transplantation |
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| HU Ye,LOU Hong qiang,He Zhong ping,WANG Lan,HE Xu ying.The Effect of T Cell Differentiation induced by mTOR Expression Via RNA Interference on the Immune Tolerance of Small Bowel Transplantation[J].Journal of Jinhua College of Profession and Technology,2014,14(6):74-79. |
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| Authors: | HU Ye LOU Hong qiang He Zhong ping WANG Lan HE Xu ying |
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| Institution: | HU Ye, LOU Hong qiang, He Zhong ping, WANG Lan, HE Xu ying (1.Jinhua Polytechnic, Jinhua 321007 China; 2.Jinhua Institute for Food and Drug Control, Jinhua 321000 China) |
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| Abstract: | Objective： To explore the effect of T cell differentiation induced by mTOR expression via RNA interference on the immune tolerance of small bowel transplantation. Methods： The directional differentiation of Foxp3^＋ Treg cells was induced by mTOR expression via shRNA interference in T cells. 30 segmental heterotopic small bowel transplants were performed in 60 male SD rats which were divided randomly into group A （mTOR-shRNA group）, group B （mTOR inhibitor RAD001 intervention） and group C （control group, saline injection transplantation）. The changes of body weight, survival time and pathological evaluation of small bowel transplantation rejection degree were examined after small bowel transplantation. Results： mTOR expression in rat bone marrow cells at mRNA and protein level in vitro can be effectively inhibited by mTOR-shRNA plasmid expression vector. Treatment of rats with mTOR- shRNA promoted Treg ceils, but inhibited Th17 ceils diffentiation. The immune tolerance of heterotopic small bowel transplantation in rat can be induced by mTOR-shRNA treatment, which resulted in significant inhibition of host versus graft reaction and prolonged graft survival. Conclusion： Inhibition of T cell mTOR expression via RNA interference promotes regulatory T cell differentiation, which help induction of immune tolerance in rat model of small bowel transplantation. Our data provide further evidence to support the notion that mTOR inhibitor RAD001 is one of the candidates that can be clinically used after transplantation. |
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| Keywords: | Immune tolerance RNA interference T lymphocytes mTOR gene small bowel transplantation |
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