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Effects of different immunosuppresants on CAN by affecting the TGF-β1 and smads signal pathway
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- Author:
- No author available
- Journal Title:
- CHINESE JOURNAL OF ORGAN TRANSPLANTATION
- Issue:
- 9
- DOI:
- 10.3760/cma.j.issn.0254-1785.2006.09.001
- Key Word:
- 免疫抑制剂;慢性移植肾肾病;转化生长因子β
Abstract： 目的 探讨不同免疫抑制剂对慢性移植肾肾病(CAN)中转化生长因子β1(TGF-β1)/Smads通路的影响及意义.方法 采用SD大鼠到Wistar大鼠的强化CAN模型,然后将模型大鼠随机分为对照组(不行处理)、环孢素A组(给予环孢素A 6 mg·kg-1·d-1)、他克莫司组(给予他克莫司0.15 mg·kg-1·d-1)、霉酚酸酯组(给予霉酚酸酯20 mg·kg-1·d-1)和西罗莫司组(给予西罗莫司0.8mg·kg-1·d-1).分别于术后4、8、12周处死动物,观察移植肾组织的病理变化,用免疫组织化学法和时荧光定量聚合酶链反应测定肾组织中TGF-β1、Smad2和Smad7蛋白及其基因的表达.结果 术后各组均呈现CAN的病理改变,环孢素A组和他克莫司组的病变程度较对照组重,而霉酚酸酯组和西罗莫司组的病变轻于对照组.术后各时间段,环孢素A组和他克莫司组TGF-β1和Smad2蛋白及其Mrna的表达明显高于对照组(P＜0.05),而Smad7蛋白及其Mrna的表达明显低于对照组(P＜0.05);霉酚酸酯组和西罗莫司组TGF-β1和Smad2蛋白及其Mrna的表达明显低于对照组(P＜0.05),而Smad7蛋白及其Mrna的表达明显高于对照组(P＜0.05).结论 发生CAN时,环孢素A和他克莫司可上调TGF-β1的表达,影响TGF-β1/Smads通路,加重其病理损害,而霉酚酸酯和西罗莫司的作用与之相反.
- [1]辛宇鹏,卢一平,张秀辉,等.大鼠原位异体肾移植硬化加快模型的建立[J].2004,(2).
- [2]Solez K,Hill CM,Gibson IW,etc.The Banff 97 working classification of renal allograft pathology.[J].1999,55(2).
- [3]Roberts AB.TGF-beta signaling from receptors to the nucleus.[J].1999,1(15).
- [4]Campistol JM,Inigo P,Larios S,etc.Role of transforming growth factor-beta1 in the progression of chronic allograft nephropathy.[J].2001,16(Suppl.1).
- [5]N, Kamada.A description of cuff techniques for renal transplantation in the rat. Use in studies of tolerance induction during combined liver grafting.[J].1985,39(1).
- [6]Xu D,Daloze P,Jolicoeur EM,etc.Combination therapy of mycophenolate mofetil and rapamycin in prevention of chronic renal allograft rejection in the rat.[J].2003,75(1).
- [7]L L, Maduzia,R W, Padgett.Drosophila MAD, a member of the Smad family, translocates to the nucleus upon stimulation of the dpp pathway.[J].1997,238(2).