Afferent Reinnervation After Lung Transplantation in the Rat

肺移植后去神经支配导致咳嗽反射丧失和局部防御机制减弱，这是肺移植后感染发生率和严重程度增加的原因。我们研究了大鼠原位左肺等移植术后不同时间间隔自发性传入神经支配的存在或缺失（n=52）。正常大鼠（n=21）和左门剥离大鼠（n=14）作为对照。静脉输注辣椒素（30mug/kg），一种刺激肺c -纤维的辣椒提取物，通过反射性心动过缓测试传入神经的生理反应。右肺动脉闭塞前后反复注射辣椒素，使肺血流全部分流至左肺或异位移植物。术后8个月或更长时间的大鼠对辣椒素的反应与正常大鼠一样，表现出强烈的反射性心动过缓。感觉神经元特异性物质的免疫组织化学染色，如降钙素基因相关肽（CGRP）和P物质，仅在移植后2个月或更长时间的右原生肺和左肺同种移植物中发现。在去神经支配8个月或更长时间的大鼠左肺胸膜内注射神经元特异性示踪剂后，仅在同侧结节神经节中发现氟金。目前的实验提供了生理学、形态学和神经学的证据，表明移植后早期被破坏的传入神经在大鼠肺等移植后8个月在同侧迷走神经中自发重建并发挥功能。

Denervation at lung transplantation results in loss of cough reflex and attenuated local defense mechanisms, accounting for increased incidence and severity of infection after lung transplantation. We studied the presence or absence of spontaneous afferent reinnervation in rats at various intervals after orthotopic left lung isografting (n=52). Normal rats (n=21) and rats undergoing left hilar stripping (n=14) served as controls. Afferent reinnervation was tested physiologically by reflex bradycardia in response to intravenous infusion of capsaicin (30mug/kg), an extract of paprika stimulating pulmonary C-fibers. Injection of capsaicin was repeated before and after right pulmonary artery occlusion to divert all pulmonary blood flow to the leftlung or isograft. Whereas rats early after surgical denervation lost the reflex after right pulmonary artery occlusion, rats 8 months or longer after surgery showed potent reflex bradycardia in response to capsaicin as did the normal rats. Immunohistochemical staining for sensory neuron specific substances, such as Calcitonin Gene-Related Peptide (CGRP) and substance P,were identified only in the right native lungs and left lung isografts 2 months or longer after transplantation. Fluoro-gold was found only in the ipsilateral nodose ganglion after left lung intrapleural injection of the neuron specific tracer in rats 8 months or longer after denervation.The current experiments provide physiologic, morphologic and neurologic evidence suggesting that afferent lung innervation, abolished early after transplantation, is spontaneously reestablished and functioning in the ipsilateral vagus nerve by 8 months after lung isografting in the rat.