Fakin Richard, Hamacher Jürg, Gugger Mathias, Gazdhar Amiq, Moser Helen, Schmid Ralph Alexander
Division of General Thoracic Surgery, University Hospital Bern, University of Bern, Switzerland.
Exp Lung Res. 2011 Nov;37(9):555-62. doi: 10.3109/01902148.2011.601785. Epub 2011 Sep 6.
The effect of prolonged electroporation-mediated human interleukin-10 (hIL-10) overexpression 24 hours before transplantation, combined with sequential human hepatocyte growth factor (HGF) overexpression into skeletal muscle on day 5, on rat lung allograft rejection was evaluated. Left lung allotransplantation was performed from Brown-Norway to Fischer-F344 rats. Gene transfer into skeletal muscle was enhanced by electroporation. Three groups were studied: group I animals (n = 5) received 2.5 μg pCIK-hIL-10 (hIL-10/CMV [cytomegalovirus] early promoter enhancer) on day -1 and 80 μg pCIK-HGF (HGF/CMV early promoter enhancer) on day 5. Group II animals (n = 4) received 2.5 μg pCIK-hIL-10 and pUbC-hIL-10 (hIL-10/pUbC promoter) on day -1. Control group III animals (n = 4) were treated by sham electroporation on days -1 and 5. All animals received daily nontherapeutic intraperitoneal dose of cyclosporin A (2.5 mg/kg) and were sacrificed on day 15. Graft oxygenation and allograft rejection were evaluated. Significant differences were found between study groups in graft oxygenation (Pao(2)) (P = .0028; group I vs. groups II and III, P < .01 each). Pao(2) was low in group II (31 ± 1 mm Hg) and in group III controls (34 ± 10 mm Hg), without statistically significant difference between these 2 groups (P = .54). In contrast, in group I, Pao(2) of recipients sequentially transduced with IL-10 and HGF plasmids was much improved, with 112 ± 39 mm Hg (vs. groups II and III; P < .01 each), paralleled by reduced vascular and bronchial rejection (group I vs. groups II and III, P < .021 each). Sequential overexpression of anti-inflammatory cytokine IL-10, followed by sequential and overlapping HGF overexpression on day 5, preserves lung function and reduces acute lung allograft rejection up to day 15 post transplant as compared to prolonged IL-10 overexpression alone.
评估移植前24小时通过电穿孔介导的人白细胞介素10（hIL-10）长期过表达，联合第5天向骨骼肌中序贯过表达人肝细胞生长因子（HGF）对大鼠肺移植排斥反应的影响。将Brown-Norway大鼠的左肺移植到Fischer-F344大鼠。通过电穿孔增强向骨骼肌的基因转移。研究了三组：第I组动物（n = 5）在第-1天接受2.5μg pCIK-hIL-10（hIL-10/巨细胞病毒[CMV]早期启动子增强子），在第5天接受80μg pCIK-HGF（HGF/CMV早期启动子增强子）。第II组动物（n = 4）在第-1天接受2.5μg pCIK-hIL-10和pUbC-hIL-10（hIL-10/pUbC启动子）。对照组III动物（n = 4）在第-1天和第5天接受假电穿孔治疗。所有动物每天接受非治疗性腹腔注射环孢素A（2.5mg/kg），并在第15天处死。评估移植物氧合和移植排斥反应。研究组之间在移植物氧合（动脉血氧分压[Pao₂]）方面发现有显著差异（P = 0.0028；第I组与第II组和第III组相比，每组P < 0.01）。第II组（31±1mmHg）和第III组对照组（34±10mmHg）的Pao₂较低，这两组之间无统计学显著差异（P = 0.54）。相比之下，在第I组中，依次用IL-10和HGF质粒转导的受体的Pao₂有很大改善，为112±39mmHg（与第II组和第III组相比，每组P < 0.01），同时血管和支气管排斥反应减轻（第I组与第II组和第III组相比，每组P < 0.021）。与单独长期过表达IL-10相比，抗炎细胞因子IL-10的序贯过表达，随后在第5天序贯和重叠过表达HGF，可在移植后第15天之前维持肺功能并减轻急性肺移植排斥反应。
