Wang Lei, Chopp Michael, Jia Longfei, Lu Xuerong, Szalad Alexandra, Zhang Yi, Zhang RuiLan, Zhang Zheng Gang
Department of Neurology, Henry Ford Hospital, 2799 W. Grand Boulevard, Detroit, MI 48202, USA.
Department of Neurology, Henry Ford Hospital, 2799 W. Grand Boulevard, Detroit, MI 48202, USA ; Department of Physics, Oakland University, Rochester, MI 48309, USA.
J Diabetes Res. 2015;2015:173656. doi: 10.1155/2015/173656. Epub 2015 Apr 7.
Peripheral neuropathy is a chronic complication of diabetes mellitus. To investigated the efficacy and safety of the extended treatment of diabetic peripheral neuropathy with thymosin β4 (Tβ4), male diabetic mice (db/db) at the age of 24 weeks were treated with Tβ4 or saline for 16 consecutive weeks. Treatment of diabetic mice with Tβ4 significantly improved motor (MCV) and sensory (SCV) conduction velocity in the sciatic nerve and the thermal and mechanical latency. However, Tβ4 treatment did not significantly alter blood glucose levels. Treatment with Tβ4 significantly increased intraepidermal nerve fiber density. Furthermore, Tβ4 counteracted the diabetes-induced axon diameter and myelin thickness reductions and the g-ratio increase in sciatic nerve. In vitro, compared with dorsal root ganglia (DRG) neurons derived from nondiabetic mice, DRG neurons derived from diabetic mice exhibited significantly decreased neurite outgrowth, whereas Tβ4 promoted neurite growth in these diabetic DRG neurons. Blockage of the Ang1/Tie2 signaling pathway with a neutralized antibody against Tie2 abolished Tβ4-increased neurite outgrowth. Our data demonstrate that extended Tβ4 treatment ameliorates diabetic-induced axonal degeneration and demyelination, which likely contribute to therapeutic effect of Tβ4 on diabetic neuropathy. The Ang1/Tie2 pathway may mediate Tβ4-induced axonal remodeling.
周围神经病变是糖尿病的一种慢性并发症。为了研究胸腺素β4（Tβ4）延长治疗糖尿病周围神经病变的疗效和安全性，对24周龄的雄性糖尿病小鼠（db/db）连续16周给予Tβ4或生理盐水治疗。用Tβ4治疗糖尿病小鼠可显著改善坐骨神经的运动（MCV）和感觉（SCV）传导速度以及热潜伏期和机械潜伏期。然而，Tβ4治疗并未显著改变血糖水平。Tβ4治疗可显著增加表皮内神经纤维密度。此外，Tβ4可抵消糖尿病引起的坐骨神经轴突直径和髓鞘厚度减小以及g比值增加。在体外，与来自非糖尿病小鼠的背根神经节（DRG）神经元相比，来自糖尿病小鼠的DRG神经元的神经突生长显著减少，而Tβ4可促进这些糖尿病DRG神经元的神经突生长。用抗Tie2中和抗体阻断Ang1/Tie2信号通路可消除Tβ4增加的神经突生长。我们的数据表明，延长Tβ4治疗可改善糖尿病引起的轴突变性和脱髓鞘，这可能是Tβ4对糖尿病神经病变治疗作用的原因。Ang1/Tie2通路可能介导Tβ4诱导的轴突重塑。
