Zuber Martina, Donnerer Josef
Institute of Experimental and Clinical Pharmacology, University of Graz, Austria.
Pharmacology. 2002 Sep;66(1):44-50. doi: 10.1159/000063254.
It has previously been shown that the capsaicin-lesioned peptidergic sensory neurons and the 6-hydroxydopamine (6-OHDA)-lesioned sympathetic noradrenergic neurons represent a useful model to study neurotrophin-induced nerve regeneration in the adult rat. The present study was aimed at investigating if the immunosuppressant drug FK506 (tacrolimus) has neuroregeneratory properties in these capsaicin- or 6-OHDA-lesioned peripheral nerves. FK506 was injected in a dose of 0.5 mg/kg/day for 10 days or in a dose of 1.5 mg/kg/day for 7 days. One day after the last FK506 injection neurotransmitter content was investigated in selected tissues. The content of the sensory neuron marker peptide calcitonin gene-related peptide (CGRP) was reduced after the capsaicin treatment in the hind paw skin by 35-40% and in the dorsal lumbar spinal cord by 48%. The treatment with FK506 did not induce a recovery of the CGRP content. Following the 6-OHDA treatment the noradrenaline content was reduced by 50-62% in the hind paw skin and by 73% in the heart atrium. FK506 alone did not increase the noradrenaline levels, whereas an additional local intraplantar treatment with nerve growth factor recovered noradrenaline levels almost completely. The expression of a marker protein for growth processes in cells of sympathetic or sensory ganglia, growth-associated protein-43, was significantly increased by the FK506 treatment. This study demonstrated that despite a stimulatory effect of FK506 on the expression of a growth-associated protein a recovery of the transmitter content is not evident in peripheral small diameter sensory or postganglionic sympathetic neurons of the adult rat.
先前的研究表明，辣椒素损伤的肽能感觉神经元和6-羟基多巴胺（6-OHDA）损伤的交感去甲肾上腺素能神经元是研究成年大鼠神经营养因子诱导神经再生的有用模型。本研究旨在调查免疫抑制剂药物FK506（他克莫司）在这些辣椒素或6-OHDA损伤的外周神经中是否具有神经再生特性。FK506以0.5mg/kg/天的剂量注射10天，或以1.5mg/kg/天的剂量注射7天。在最后一次FK506注射后一天，对选定组织中的神经递质含量进行了研究。辣椒素处理后，后爪皮肤中感觉神经元标记肽降钙素基因相关肽（CGRP）的含量降低了35%-40%，在背侧腰脊髓中降低了48%。FK506治疗并未诱导CGRP含量的恢复。6-OHDA处理后，后爪皮肤中的去甲肾上腺素含量降低了50%-62%，心房中降低了73%。单独使用FK506并没有增加去甲肾上腺素水平，而额外的足底局部神经生长因子治疗几乎完全恢复了去甲肾上腺素水平。FK506处理显著增加了交感或感觉神经节细胞中生长相关蛋白43（一种生长过程标记蛋白）的表达。这项研究表明，尽管FK506对生长相关蛋白的表达有刺激作用，但在成年大鼠的外周小直径感觉神经元或节后交感神经元中，神经递质含量的恢复并不明显。
