AXONAL-TRANSPORT OF ENDOGENOUS NERVE GROWTH-FACTOR (NGF) AND NGF RECEPTOR IN EXPERIMENTAL DIABETIC NEUROPATHY
AXONAL-TRANSPORT OF ENDOGENOUS NERVE GROWTH-FACTOR (NGF) AND NGF RECEPTOR IN EXPERIMENTAL DIABETIC NEUROPATHY
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DOI：
10.1006/exnr.1994.1181
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发表时间：
1994-11-01
影响因子：
5.3
通讯作者：
KREUTZBERG, GW
中科院分区：
文献类型：
--
作者：
HELLWEG, R;RAIVICH, G;KREUTZBERG, GW
越来越多的证据表明，剥夺逆行转运的神经营养蛋白神经生长因子（NGF）的帐户已知发生在实验性糖尿病神经病变的一些功能缺陷。在这里，我们研究了内源性神经生长因子，神经生长因子受体（NGFR），和NGFR饱和度（NGF/NGFR比）在大鼠坐骨神经轴突运输的变化后，2个月的链脲佐菌素（STZ）诱导的糖尿病。与赋形剂处理的对照大鼠（血糖：6-12 mM）相比，在STZ处理的糖尿病动物（血糖：33-62 mM）中，NGF的逆行转运非常明显地减少了50%（P < 0.001）。在STZ处理的大鼠亚群中没有观察到NGF轴突运输的显著减少（反应差），葡萄糖水平接近正常（范围：9-12 mM）。在任何组中均未观察到NGFR逆行转运的变化。然而，与对照组大鼠相比，STZ糖尿病患者的表观NGFR饱和度降低了45%（P < 0.002），而STZ低反应者的NGFR饱和度没有变化。糖尿病患者NGFR饱和度和NGF逆行转运量与血糖浓度呈负相关（r（2）分别为0.47和0.55，P < 0.0001）。这些发现表明，虽然NGFR表达在STZ-糖尿病神经病变模型中是正常的，但在糖尿病患者中观察到的受体饱和度的显著降低可能反映了低外周NGF水平，这导致糖尿病大鼠神经元NGF的明显剥夺。(C)1994年出版社出版。
There is increasing evidence that deprivation of the retrogradely transported neurotrophic protein nerve growth factor (NGF) accounts for some functional deficits known to occur in experimental diabetic neuropathy. Here we have studied changes in the axonal transport of endogenous NGF, NGF receptor (NGFR), and NGFR saturation (NGF/NGFR ratio) in the rat sciatic nerve after 2 months of streptozotocin (STZ)-induced diabetes mellitus. Compared with vehicle-treated control rats (blood glucose: 6-12 mM), there was a very clear reduction in the retrograde transport of NGF by 50% (P < 0.001) in STZ-treated, diabetic animals (blood glucose: 33-62 mM). No significant reduction in NGF axonal transport was observed in a subpopulation of STZ-treated rats (poor responders) with nearly normal glucose levels (range: 9-12 mM). No change was observed in any group in the retrograde transport of NGFR. Compared with control rats, however, the apparent NGFR saturation was reduced by 45% (P < 0.002) in STZ diabetics, whereas no change in NGFR saturation was observed in the STZ-poor responders. Moreover, the NGFR saturation and amount of retrogradely transported NGF were negatively correlated to the individual glucose concentration in diabetics (r(2) = 0.47 and 0.55, respectively; P < 0.0001). These findings indicate that, while NGFR expression is normal in the STZ-diabetic neuropathy model, the marked decrease in receptor saturation observed in diabetics may reflect low peripheral NGF levels, which in consequence leads to the apparent deprivation of neuronal NGF in diabetic rats. (C) 1994 Academic Press, Inc.