Department of Hand and Foot Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, China.
Department of Hand and Foot Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, China.
Life Sci. 2020 Sep 1;256:117959. doi: 10.1016/j.lfs.2020.117959. Epub 2020 Jun 10.
Resveratrol has the ability to promote functional recovery after sciatic nerve crush injury (SNCI), though the mechanism through which this occurs in not fully understood. Resveratrol can promote autophagy, a key process in Wallerian degeneration; thus, we hypothesized that resveratrol could promote recovery from SNCI by promoting Schwann cell autophagy and acceleration of Wallerian degeneration. Motor function recovery was assessed by calculating Sciatic Function Indexes (SFIs) at days 7, 14, 21, 28 post SNCI. Autophagy and myelin clearance were assessed by microtubule-associated protein light chain 3B (LC3B) and myelin protein zero (MPZ) immunofluorescence and Western blot analysis on the fourth day after SNCI. The autophagy of Schwann cells following resveratrol administration was quantified by immunofluorescence in RSC96 cells. Immunofluorescence and Transmission electron microscopy (TEM) were also used in Resveratrol treated sciatic nerve four days post-SNCI to find LC3B positive areas and typical double membrane structures represent for autophagy. The SNCI+resveratrol (crush+Res) groups recovered faster than the SNCI+vehicles (crush+V) group. On day four, almost all of the myelin had regenerated in the crush+Res rats, while the crush+V group's myelin remained intact and the expression levels of LC3-II/I was the highest. On day 28 post-injury, both the control and crush+Res groups' myelin neurofibers reached peak numbers as did the thickness of the myelin sheath. Both in vitro and in vivo immunofluorescence showed that LC3B was colocalized with Schwann cells. This is the first study to observe that resveratrol can promote recovery from SCNI by accelerating the myelin clearance process by promoting autophagy of Schwann cells.
白藜芦醇具有促进坐骨神经挤压损伤（SNCI）后功能恢复的能力，但其作用机制尚不完全清楚。白藜芦醇可以促进自噬，这是 Wallerian 变性的关键过程；因此，我们假设白藜芦醇可以通过促进施万细胞自噬和加速 Wallerian 变性来促进 SNCI 的恢复。在 SNCI 后第 7、14、21 和 28 天通过计算坐骨神经功能指数（SFIs）评估运动功能恢复。在 SNCI 后第 4 天通过微管相关蛋白轻链 3B（LC3B）和髓鞘蛋白零（MPZ）免疫荧光和 Western blot 分析评估自噬和髓鞘清除。通过 RSC96 细胞中的免疫荧光定量施万细胞中白藜芦醇给药后的自噬。在 SNCI 后 4 天用白藜芦醇处理的坐骨神经进行免疫荧光和透射电子显微镜（TEM）也发现 LC3B 阳性区域和代表自噬的典型双层结构。与 SNCI+vehicles（挤压+V）组相比，SNCI+resveratrol（挤压+Res）组恢复更快。在第 4 天，挤压+Res 大鼠的几乎所有髓鞘都已再生，而挤压+V 组的髓鞘保持完整，LC3-II/I 的表达水平最高。在损伤后第 28 天，对照组和挤压+Res 组的髓鞘神经纤维数量都达到峰值，髓鞘鞘厚度也达到峰值。体外和体内免疫荧光均显示 LC3B 与施万细胞共定位。这是第一项观察到白藜芦醇通过促进施万细胞自噬加速髓鞘清除过程来促进 SNCI 恢复的研究。
