Department of Anatomy, The University of Hong Kong, Hong Kong SAR, China.
J Neuropathol Exp Neurol. 2010 Mar;69(3):294-305. doi: 10.1097/NEN.0b013e3181d26487.
This study examined the role of aldose reductase (AR) in diabetes-associated impaired nerve regeneration using thy1-YFP (YFP) mice. Sciatic nerves of nondiabetic and streptozotocin-induced diabetic AR(+/+)YFP and AR(-/-)YFP mice were transected after 4 weeks of diabetes. Wallerian degeneration and nerve regeneration were evaluated at 1 and 2 weeks postaxotomy by fluorescence microscopy. Motor nerve conduction velocity recovery and regenerating nerve morphometric parameters were determined at 10 and 20 weeks, respectively. There was no difference in the extent of Wallerian degeneration, size of regenerating stump, motor nerve conduction velocity recovery, or caliber of regenerating fibers between nondiabetic AR(+/+)YFP and AR(-/-)YFP mice. In diabetic AR(+/+)YFP mice, Wallerian degeneration was delayed, associated with slower macrophage invasion and abnormal vascularization. Those mice had smaller regenerating stumps, slower motor nerve conduction velocity, and smaller regenerating fibers compared with nondiabetic mice. These features of impaired nerve regeneration were largely attenuated in diabetic AR(-/-)YFP mice. Retarded macrophage invasion and vascularization associated with Wallerian degeneration were normalized in diabetic AR(-/-)YFP mice. These results indicate that AR plays an important role in diabetes-associated impaired nerve regeneration, in part by affecting vascularization and macrophage invasion during Wallerian degeneration. The thy1-YFP mice are valuable tools for further investigation of the mechanism of diabetes-associated nerve regeneration.
本研究使用 thy1-YFP（YFP）小鼠探讨醛糖还原酶（AR）在糖尿病相关神经再生受损中的作用。糖尿病 4 周后，横断非糖尿病和链脲佐菌素诱导的糖尿病 AR(+/+)YFP 和 AR(-/-)YFP 小鼠的坐骨神经。轴突切断后 1 和 2 周，通过荧光显微镜评估 Wallerian 变性和神经再生。分别在 10 和 20 周时测定运动神经传导速度恢复和再生神经形态计量参数。非糖尿病 AR(+/+)YFP 和 AR(-/-)YFP 小鼠之间 Wallerian 变性的程度、再生残端的大小、运动神经传导速度的恢复或再生纤维的口径没有差异。在糖尿病 AR(+/+)YFP 小鼠中，Wallerian 变性延迟，伴有巨噬细胞浸润和血管异常。与非糖尿病小鼠相比，这些小鼠的再生残端较小，运动神经传导速度较慢，再生纤维较小。糖尿病 AR(-/-)YFP 小鼠中神经再生受损的这些特征在很大程度上减弱。与 Wallerian 变性相关的巨噬细胞浸润和血管化延迟在糖尿病 AR(-/-)YFP 小鼠中得到纠正。这些结果表明，AR 在糖尿病相关神经再生受损中起重要作用，部分通过影响 Wallerian 变性过程中的血管生成和巨噬细胞浸润。thy1-YFP 小鼠是进一步研究糖尿病相关神经再生机制的有价值的工具。
