受体小鼠诱导一氧化碳延长同种移植心存活时间实验研究

Experimental study of carbon monoxide with methylene chloride in recipients prolongs cardiac allograft survival in mice

目的观察受体小鼠诱导一氧化碳(CO)对同种移植心存活时间的影响,并探讨其可能的机制。方法建立小鼠颈部异位心脏移植模型(C57BL/6→Balb/c小鼠)。受体小鼠自移植前1 d至移植后第6天(MC1周组)或至第13天(MC2周组)以二氯甲烷(MC)100 mg/kg体质量灌胃,或以同体积不含MC的橄榄油灌胃(Tx组)。观测移植心存活时间,于移植后第6、10天检测受体血清TNF-α、IL-10的含量和移植心肌TNF-α、IL-10 mRNA的表达及病理学改变。结果受体以MC灌胃后血液中碳氧血红蛋白(COHb)浓度在3 h达到峰值;与Tx组比较,受体诱导CO(MC组)可以明显延长移植心存活时间,差异有统计学意义(P<0.01),降低血清TNF-α的含量和移植心肌TNF-αmRNA的表达,差异有统计学意义(P<0.01),心肌的病理学改变明显减轻,以MC2周组明显;各组血清IL-10含量和移植心肌IL-10 mRNA表达差异无统计学意义(P>0.05)。结论受体小鼠诱导CO明显延长同种移植心的存活时间,其主要机制可能与CO降低受体血清TNF-α含量和移植心肌TNF-αmRNA表达有关。

Objective To investigate whether induction of carbon monoxide（CO） in recipients could prolong cardiac graft survival and the possible mechanisms in mice.Methods Inbred male C57BL/6 mice were used as donors and Balb/c mice were used as recipients to establish allogenic heart transplantation model.Recipients were treated with either methylene chloride（100mg/kg,per os,Group MC） or olive oil（Group Tx） day 1 prior to transplantation to day 6 posttransplantation（Group MC1w） or day 13 posttransplantation（Group MC2w）.Recipients mice were killed at day 6 and day 10 after transplantation for serum and cardiac graft samples（n=5～6 for each time point）.The serum TNF-α and IL-10 and the TNF-α mRNA and IL-10 mRNA in cardiac grafts were measured,respectively.The survival of cardiac grafts was recorded.Results Following MC application serum COHb peaked within 3h in recipients.Compared with Group Tx,induction of CO in recipients,especially in Group MC2w,prolonged significantly the cardiac graft survival（P0.01）,down-regulated the levels of serum TNF-α and cardiac graft TNF-α mRNA（P0.01）,and decreased lymphocyte and monocyte infiltration in cardiac grafts.The levels of serum IL-10 and graft IL-10 mRNA did not differ between the groups（P0.05）.Conclusion Induction of carbon monoxide in recipients could prolong cardiac graft survival via down-regulation of the levels of serum TNF-α and TNF-α mRNA in grafts in mice.