小鼠供肾选择性缺失Ndst1对肾移植术后急性排斥反应的影响及其机制研究

Effect and mechanism research of selective deletion of Ndst1 in donor kidney on acute rejection after renal transplantation in mouse models

    摘要
  • 摘要:
      目的  探讨小鼠供肾选择性缺失N-脱乙酰基酶-N-磺基转移酶（Ndst）1对肾移植术后受体小鼠急性排斥反应的影响及其机制。
      方法  建立小鼠肾移植模型。根据品系和处理方式不同，将小鼠分为3组：野生型（WT）组（n=10）、Ndst1-/-组（n=9）、黏液瘤病毒T7蛋白（M-T7）治疗组（n=7）。术后第10日对各组小鼠实施安乐死，对各组小鼠移植肾分别进行病理学检查和糖胺聚糖（GAGs）中的双糖硫酸乙酰肝素（HS）和硫酸软骨素（CS）含量分析。分析病理学评分与双糖含量变化的相关性。
      结果  与WT组比较，Ndst1-/-组和M-T7治疗组小鼠移植肾组织的早期排斥反应的总体病理学评分显著降低（均为P < 0.05）。与WT组比较，Ndst1-/-组小鼠移植肾组织中HS的6-O硫酸化比例、D0S6含量显著增加（均为P < 0.05），CS的D0A4和D2A4含量显著下降（均为P < 0.05）。与WT组比较，M-T7治疗组小鼠移植肾组织中HS的6-O硫酸化比例、CS的6-O硫酸化和2-O硫酸化比例、HS的D0S6和D2S6含量均显著增加（均为P < 0.05），HS的D2A0含量、CS的D0A4和D2A4含量明显降低（均为P < 0.05）。小鼠移植肾组织中双糖含量变化与急性排斥反应相关病理学评分均具有相关性（均为P < 0.05）。
      结论  供肾选择性缺失Ndst1可减轻肾移植术后的急性排斥反应，其机制可能与移植肾组织中双糖HS的6-O硫酸化比例增加有关。

     

    Abstract:
      Objective  To investigate the effect and mechanism of selective deletion of N-deacetylase-N-sulfotransferase (Ndst) 1 in donor kidney on the acute rejection after renal transplantation in the recipient mice.
      Methods  A mouse model undergoing renal transplantation was established. The mice were divided into 3 groups according to the strains of mice and treatment: wild type (WT) group (n=10), Ndst1-/- group (n=9) and myxoma virus T7 protein(M-T 7)treatment group (n=7). The mice were euthanized at postoperative 10 d. Pathological examination and the content of disaccharide heparan sulfate (HS) and chondroitin sulfate (CS) in glycosaminoglycans (GAGs) were analyzed. The correlation between pathological score and changes of disaccharide content was analyzed.
      Results  Compared with the WT group, the overall pathological scores of early rejection of the transplanted kidney tissues were significantly lower in the Ndst1-/- and M-T7 treatment groups (both P < 0.05). Compared with the WT group, the percentage of 6-O sulfation and the content of D0S6 in HS were significantly increased, whereas the contents of D0A4 and D2A4 in CS were significantly decreased in the transplanted kidney tissues in the Ndst1-/- group (all P < 0.05). Compared with the WT group, the percentage of 6-O sulfation in HS, the percentages of 6-O sulfation and 2-O sulfation in CS and the contents of D0S6 and D2S6 in HS were significantly increased, whereas the content of D2A0 in HS, the contents of D0A4 and D2A4 in CS were significantly decreased in the transplanted kidney tissues in the M-T7 treatment group (all P < 0.05). The changes of disaccharide content in the transplanted kidney tissues of mice were significantly correlated with pathological scores related to acute rejection (all P < 0.05).
      Conclusions  Selective deletion of Ndst1 of the donor kidney can alleviate acute rejection after renal transplantation, and the mechanism may be related to the increased 6-O sulfation ratio of disaccharide HS in the transplanted kidney tissues.

     

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