Xia Nan, Xu Jin-Mei, Zhao Nan, Zhao Qing-Song, Li Ming, Cheng Zhi-Feng
Department of Endocrinology and Metabolism, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Endocrinology and Metabolism, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
Neurosci Lett. 2015 Jun 15;597:84-9. doi: 10.1016/j.neulet.2015.04.038. Epub 2015 Apr 24.
Neuropathy is observed in 50% of diabetic patients with diabetic foot. This study attempted to explore the potential role of human mesenchymal stem cells-umbilical cord blood (hMSCs-UC) in femoral nerve (FN) neuropathy. The model rats were established by one time administration of streptozotocin and empyrosis on the dorsal hind foot. At 3d, 7d, 14d after treatment with hMSCs-UC or saline through left femoral artery, the serum NGF was examined by ELISA; NF-200 expression in FN was evaluated by immunohistochemistry; the diameter and roundness of FN, the ratio of capillary and muscular fiber of gastrocnemius were calculated under light microscope; and neuronal degenerations, such as demyelization, axonal atrophy, and loose arrangement of nerve fibers, were observed by electronic microscope. The results showed that, in hMSCs-UC-treated model rats, serum NGF was increased with higher positive rate of NF-200. Although the difference in FN diameters was not established among groups, improvement of roundness of FN was confirmed with increase in the numbers of capillary in FN-innervated gastrocnemius; additionally, degenerative neuropathy was significantly improved. Importantly, the functional study of electroneurogram (ENG) showed that, slowed conduction of FN in model rats was significantly restored by hMSCs-CU treatment. These data suggested that hMSCs-UC-treatment partially reverse the neuronal degeneration and nerve function of FN, which might be contributed by the upregulation of NGF with dramatic angiogenesis in FN-innervated gastrocnemius, consequently reversing neuronal structure and function, preventing or curing foot ulceration.
50%的糖尿病足患者会出现神经病变。本研究旨在探讨人间充质干细胞-脐带血（hMSCs-UC）在股神经（FN）神经病变中的潜在作用。通过一次性给予链脲佐菌素并在后足背部造成烫伤来建立模型大鼠。经左股动脉给予hMSCs-UC或生理盐水治疗后3天、7天、14天，采用ELISA检测血清NGF；通过免疫组化评估FN中NF-200的表达；在光学显微镜下计算FN的直径和圆度、腓肠肌的毛细血管与肌纤维比例；通过电子显微镜观察神经元变性，如脱髓鞘、轴突萎缩和神经纤维排列疏松等情况。结果显示，在接受hMSCs-UC治疗的模型大鼠中，血清NGF升高，NF-200阳性率更高。尽管各组间FN直径差异未确立，但证实FN圆度有所改善，且FN支配的腓肠肌中毛细血管数量增加；此外，退行性神经病变明显改善。重要的是，神经电图（ENG）功能研究表明，hMSCs-CU治疗显著恢复了模型大鼠FN的传导减慢。这些数据表明，hMSCs-UC治疗可部分逆转FN的神经元变性和神经功能，这可能是由于FN支配的腓肠肌中NGF上调并伴有显著的血管生成，从而逆转神经元结构和功能，预防或治愈足部溃疡。
