Streptozotocin-induced diabetes causes metabolic changes and alterations in neurotrophin content and retrograde transport in the cervical vagus nerve.
Streptozotocin-induced diabetes causes metabolic changes and alterations in neurotrophin content and retrograde transport in the cervical vagus nerve.
复制标题
链脲佐菌素诱导的糖尿病会引起代谢变化、神经营养蛋白含量的改变以及颈迷走神经的逆行运输。
DOI：
10.1006/exnr.2001.7673
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Helke,CJ
中科院分区：
文献类型：
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作者：
Lee,PG;Hohman,TC;Cai,F;Regalia,J;Helke,CJ
神经营养因子的异常可获得性，如神经生长因子(NGF)，已被认为与糖尿病躯体感觉多发性神经病有关。然而，神经营养因子在糖尿病自主神经病变中的作用尚不清楚，尤其是在内脏传入和自主运动功能中起关键作用的迷走神经。为探讨高血糖对该系统神经营养因子含量和转运的影响，对链脲佐菌素(STZ)诱导的糖尿病大鼠8、16、24周的颈迷走神经进行了研究。迷走神经己糖(葡萄糖和果糖)和多元醇(山梨醇)水平的升高，以及它们与胰岛素治疗的正常化，证实了STZ治疗导致了高血糖诱导的神经代谢异常。对非糖尿病对照组大鼠、STZ诱导的糖尿病大鼠和胰岛素治疗的糖尿病大鼠颈迷走神经中神经营养因子(NGF和神经营养因子-3；NT-3)的含量和轴突运输进行了检测。糖尿病大鼠完整迷走神经的NGF含量在8周和16周(24周)有所增加，但NT-3含量无明显变化。使用双结扎模型评估内源性神经营养因子的运输，发现NGF和NT-3在糖尿病晚期(16周和24周)的颈迷走神经中的逆行运输显著减少。糖尿病大鼠和正常大鼠迷走神经中NGF和NT-3的顺行转运不明显。这些数据表明，迷走神经NGF的增加是对糖尿病高血糖的早期但短暂的反应，继发于逆行轴突运输减少的神经元对NGF和NT-3的获取减少可能在糖尿病引起的迷走神经损伤中发挥作用。
Abnormal availability of neurotrophins, such as nerve growth factor (NGF), has been implicated in diabetic somatosensory polyneuropathy. However, the involvement of neurotrophins in diabetic neuropathy of autonomic nerves, particularly the vagus nerve which plays a critical role in visceral afferent and in autonomic motor functions, is unknown. To assess the effects of hyperglycemia on the neurotrophin content and transport in this system, cervical vagus nerves of streptozotocin (STZ)-induced diabetic rats were studied at 8, 16, and 24 weeks after the induction of diabetes. Elevations in vagus nerve hexose (glucose and fructose) and polyol levels (sorbitol), and their normalization with insulin treatment, verified that the STZ treatment resulted in hyperglycemia-induced metabolic abnormalities in the nerve. Neurotrophin (NGF and neurotrophin-3; NT-3) content and axonal transport were assessed in the cervical vagus nerves from nondiabetic control rats, STZ-induced diabetic rats, and diabetic rats treated with insulin. The NGF, but not the NT-3, content of intact vagus nerves from diabetic rats was increased at 8 and 16 weeks (but not at 24 weeks). Using a double-ligation model to assess the transport of endogenous neurotrophins, the retrograde transport of both NGF and NT-3 was found to be significantly reduced in the cervical vagus nerve at later stages of diabetes (16 and 24 weeks). Anterograde transport of NGF or NT-3 was not apparent in the vagus nerve of diabetic or control rats. These data suggest that an increase in vagus nerve NGF is an early, but transient, response to the diabetic hyperglycemia and that a subsequent reduction in neuronal access to NGF and NT-3 secondary to decreased retrograde axonal transport may play a role in diabetes-induced damage to the vagus nerve.