摘要
背景:雷公藤多甙所具有的多种免疫调节作用,是否可于肾移植慢性排斥,缺乏严密的动物实验研究和多中心、大样本临床试验研究证据的支持。目的:观察雷公藤多甙对大鼠肾移植慢性排斥的作用。方法:选用SD大鼠为供体,Wistar大鼠为受体,制作SD-Wistar大鼠肾移植慢性排斥模型,完整保留受体右肾作为每个移植肾的内对照。所有受体均于移植后10d内接受小剂量环孢素抑制急性排斥反应。移植成功受体随机分成治疗组与对照组,治疗组自移植后10d起每日经胃灌服雷公藤多甙,对照组给予相同容量的生理盐水,连续灌服至移植后12周。移植后12周收获动物,取受体移植肾组织送检组织病理学,并用免疫组织化学染色法检测移植肾转化生长因子β1的表达。结果与结论:移植后12周,两组受体移植肾均存活,体积较正常右肾略小,色泽较苍白,出现不同程度的单个核细胞浸润、肾小球硬化、肾小管萎缩、间质纤维化和小动脉内膜纤维性增厚等慢性排斥组织病理学改变。治疗组大鼠移植肾组织的病理改变明显轻于对照组(P<0.01)。两组所有受体自身右肾均未出现任何组织病理学改变。转化生长因子β1主要在治疗组和对照组的肾小管、间质表达,治疗组肾组织的转化生长因子β1表达明显低于对照组(P<0.01)。提示,雷公藤多甙能够减轻大鼠移植肾慢性排斥模型移植肾组织病理学损害,下调移植肾组织转化生长因子β1的表达可能是其作用机制之一。
BACKGROUND：Tripterygium wilfordii polyglucoside possess a variety of immune regulation. Whether it can be used for chronic renal allograft rejection needs animal experiments as well as multi-center, large-sample clinical trials. OBJECTIVE：To explore the effect of TWP on chronic renal allograft rejection in rats. METHODS：Orthotropic kidney transplantation was performed in strain combinations of SD-Wistar. The native kidney of the recipients were kept and used as an internal control. All recipients received a short course treatment of cyclosporine A （CsA microemulsion） （2 mg/kg/d for 10 days i.p） after transplantation to prevent acute rejection to establish chronic renal allograft rejection model. Fifteen successful recipient rats were randomized into TWP-treating group （n=8） and control group （n=7）. The recipient rats of the two groups were treated with TWP at doses of 30 mg/kg （TWP-treating group） or the same volume of 0.9% saline solution （control group） per day from day 10 until week 12 after transplantation. All recipient rats were killed in week 12 after transplantation, the histology examination of grafts and native kidneys was performed in parallel according to the Banff 07 working classification for renal allograft pathology. Graft histology was quantified by using the Banff sum score. Immunohistochemistry of transforming growth factor-β1 （TGF-β1） of each allograft was examined and was semiquantitatively evaluated. RESULTS AND CONCLUSION：All allografts of each group survived up to 12 weeks after transplantation and develop chronic renal allograft rejection, characterized by neointimal hyperplasia, interstitial fibrosis, tubular atrophy, glomerulosclerosis and mononuclear cell infiltration. Compared with those in the control group, the Banff sum scores and TGF-β1 expressions in the renal allograft tissues were significantly decreased in the TWP-treating group in week 12 （ P 0.01 for both）. The native kidney of recipients of each group showed no inflammation or histological alterations. In conclusion, TWP effectively reduces the histological damages and the expression of TGF-β1 in the renal allograft tissues and may be used as a new agent to treat chronic renal allograft rejection.
出处
《中国组织工程研究与临床康复》
CAS
CSCD
北大核心
2011年第18期3319-3322,共4页
Journal of Clinical Rehabilitative Tissue Engineering Research
基金
泉州市科技计划项目(2009Z39)
课题名称:丹参联合雷公藤多甙防治同种异体肾移植慢性移植肾肾病的实验研究~~
