Vagal stimulation in brain dead donor rats decreases chronic allograft nephropathy in recipients
Vagal stimulation in brain dead donor rats decreases chronic allograft nephropathy in recipients
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DOI：
10.1093/ndt/gft451
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发表时间：
2014-03-01
影响因子：
6.1
通讯作者：
Yard, Benito A.
中科院分区：
文献类型：
--
作者：
Hoeger, Simone;Fontana, Johann;Yard, Benito A.
背景。尽管在急性同种异体移植排斥模型中，脑死亡（BD）供者的迷走神经刺激导致受体肾功能改善，但其对慢性同种异体移植肾病的影响尚不清楚。在本研究中，我们评估供体迷走神经刺激对慢性同种异体移植模型存活、肾功能和组织学的影响。诱导Fisher大鼠脑死亡，其中一组（BD +迷走神经）在BD全过程（6 h）内进行电刺激。未受刺激的BD Fisher供体大鼠作为对照。异体Lewis大鼠作为受体，不给予免疫抑制药物。每两周采集一次血样和尿样。对采集的同种异体移植物进行班夫分类。迷走神经刺激BD供体可改善受体的存活率。从肌酐清除率的改善来看，这些受体的长期肾功能明显改善。Banff分级显示BD +迷走神经组血管病变和小管病变明显减少。总之，我们的数据表明，对BD供者进行迷走神经刺激对肾移植结果有持久的有益影响。因此，在BD供体中激活胆碱能抗炎途径可能是一种新的治疗方式，可以减少慢性同种异体移植肾病，而不会对受体产生任何副作用。
Background. Although it has been shown that a vagus nerve stimulation of brain dead (BD) donors leads to an improvement of renal function in recipients in an acute allograft rejection model, its influence on chronic allograft nephropathy is still unknown. In the present study, we assessed the influence of donor vagus nerve stimulation on survival, renal function and histology in a chronic allograft model.Methods. Brain death was induced in Fisher rats, and electrostimulation of the vagus nerve was applied in one group (BD + vagus) during the whole course of BD (6 h). Unstimulated BD Fisher donor rats served as controls. Allogeneic Lewis rats were used as recipients and no immunosuppressive medication was administered. Blood and urine samples were collected every second week. Banff classification was assessed from harvested allografts.Results. Vagal stimulation of BD donors resulted in an improved survival of recipients. Long-term renal function was significantly better in these recipients as reflected by improved creatinine clearance. Banff classification revealed significantly reduced vasculopathy and less tubulopathy in the BD + vagus group.Conclusions. In conclusion, our data demonstrate a long-lasting beneficial effect of vagus nerve stimulation in BD donors on the renal transplantation outcome. Hence, activation of the cholinergic anti-inflammatory pathway in BD donors may represent a novel therapeutic modality to reduce chronic allograft nephropathy without any side effects for the recipient.