Impaired prosaposin secretion during nerve regeneration in diabetic rats and protection of nerve regeneration by a prosaposin-derived peptide.
Impaired prosaposin secretion during nerve regeneration in diabetic rats and protection of nerve regeneration by a prosaposin-derived peptide.
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DOI：
10.1097/nen.0b013e31817e23f4
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发表时间：
2008-07
影响因子：
3.2
通讯作者：
Calcutt NA
中科院分区：
文献类型：
--
作者：
Jolivalt CG;Vu Y;Mizisin LM;Mizisin AP;Calcutt NA
鞘脂激活蛋白原既是鞘脂激活蛋白的前体，又是一种分泌的神经营养因子和髓鞘营养因子。由于周围神经再生在糖尿病中受损，我们通过收集分泌到连接横断坐骨神经末端的桥接管中的神经内膜液来测量对照和链脲佐菌素糖尿病大鼠的鞘脂激活蛋白原蛋白水平。与对照组相比，糖尿病大鼠神经内膜液中的鞘脂激活蛋白原蛋白水平显著降低，近端神经残端中的鞘脂激活蛋白原蛋白水平升高。为了研究鞘脂激活蛋白原衍生肽是否可以促进神经再生，在坐骨神经挤压后用鞘脂激活蛋白TX14（A）处理大鼠。在对照组大鼠中，TX14（A）对未损伤的神经没有影响，但缩短了神经挤压后的趾伸展恢复时间。在糖尿病大鼠中，通过校正未损伤神经中的热痛觉减退、福尔马林诱发的痛觉过敏和传导减慢证实了丙沙肽TX14（A）的功效。该肽还防止了糖尿病引起的神经再生距离和再生轴突的平均轴突直径的异常，而脚趾伸展的延迟恢复没有得到改善。TX14（A）可减轻对照组和糖尿病组大鼠失神经肌肉萎缩。这些结果表明，神经损伤后鞘脂激活蛋白原分泌减少可能导致糖尿病大鼠的再生率受损，并且prosaptide TX14（A）可以改善神经再生的各个方面。
Prosaposin is both a precursor of sphingolipid activator proteins and a secreted neurotrophic and myelinotrophic factor. Because peripheral nerve regeneration is impaired in diabetes mellitus, we measured prosaposin protein levels from control and streptozotocin-diabetic rats by collecting endoneurial fluid secreted into a bridging tube connecting the ends of transected sciatic nerve. Prosaposin protein levels were significantly reduced in endoneurial fluid from diabetic rats and increased in the proximal nerve stump compared to controls. To investigate whether a prosaposin-derived peptide could improve nerve regeneration, rats were treated with prosaptide TX14(A) following sciatic nerve crush. In control rats, TX14(A) was without effect in the uninjured nerve but shortened toe spread recovery time after nerve crush. In diabetic rats, efficacy of prosaptide TX14(A) was confirmed by correction of thermal hypoalgesia, formalin-evoked hyperalgesia and conduction slowing in the uninjured nerve. The peptide also prevented diabetes-induced abnormalities in nerve regeneration distance and mean axonal diameter of regenerated axons, whereas delayed recovery of toe spread was not improved. Muscle denervation atrophy was attenuated by TX14(A) in both control and diabetic rats. These results suggest that reduced prosaposin secretion after nerve injury may contribute to impaired regeneration rates in diabetic rats and that prosaptide TX14(A) can improve aspects of nerve regeneration.