抗CD-40L单抗加小剂量、短程CsA对肝移植大鼠生存期和Th1／Th2平衡偏移的影响

Effects of anti-CD40L pins short-course CsA on survival and Th1/Th2 cytokine balance in rats after orthotopic liver transplantation

目的采用抗CD-40L单抗加小剂量CsA的联合免疫治疗，观察其对大鼠肝移植受体生存时间和Th1／Th2细胞因子谱变化的影响。方法在建立稳定大鼠肝移植模型的基础上，将整个实验分为4组。A组（同基因对照组）：SD→SD；B组（同种异体基因免疫排斥组）：SD→Wistar，不用任何治疗措施；C组：SD→Wistar，CsA应用d1～d5；D组：SD→Wistar，CsA应用d1～d5加抗CD-40L（CD-154）单抗应用d0、d2。观察各组大鼠肝移植受体生存时间，移植后第7天用ELISA法检测外周血细胞因子水平。结果A组、D组受体大鼠均可长期存活，B组生存时间仅为（13．8±2．4）d。IL-2、IFN-γ在B组的血清水平显著高于其余各组（P〈0.05），TNF-α在B组的表达水平高于不同免疫抑制组，但差异无显著统计学意义。IL-4、IL10较A组均有所增加，尤其D组的IL-10表达水平较B组显著增高（P〈0.05）。结论抗CD-40L单抗加小剂量CsA（伴或不伴DSBT）联合免疫治疗，可有效延长大鼠肝移植受体的生存时间，Th2类细胞因子的高水平表达与诱导移植耐受、抑制排斥反应有重要关联，有助于大鼠肝移植受体和移植肝的长期存活。

Objective To study the infLuence of anti-CD40L pLus short-course CsA on recipient survival ancl Th1/Th2 cytokine profile. Methods The recipient rats were divided into the following groups： group A： SD→SD, group B： SD→Wistar without any treatment, group C： SD→Wistar with CsA monotherapy from dl to dS, group d： SD→ Wistar with CsA from dl to d5 and anti-CD40L mAb on d0 ancl d2. The recipient survival was observed. On the post-transplant d7, ELIS was employed to detect the expression level of cytokines in peripheral blood. Results The survival time of recipients was significantly longer in group A ancl D than in group B. The serum levels of IL-2 ancl IFN-γ in group B were markedly higher than those in other 3 groups. However, the serum levels of IL-4 and IL-10 were remarkably higher in group D than in group B （P〈0.05）. Conclnsion The combined immunotherapy can prolong graft survival time. The high expression level of Th2 cytokines is beneficial to long-term survival of recipients and graft.