Fu Mingfu, Zhang Fenghua, Song Yanli, Wang Jianhang
Department of Orthopedic Surgery, Yantaishan Hospital, 10087 Keji Avenue, Laishan District, Yantai, Shandong, 264003, China.
Neurochem Res. 2025 Apr 25;50(3):152. doi: 10.1007/s11064-025-04402-1.
Salvianolic acid A (SalA) is a phenolic acid of Salvia miltiorrhiza with the effects of anti-oxidant and immunoenhancing medicinal properties. In this study, we investigated the activities of SalA on the neurorestorative function and the autophagy-regulated NLRP3 inflammasome in sciatic nerve injury (SNI) rats and schwann cells. Sciatic nerve compression model rats were constructed, the sciatic nerve function index and gastrocnemius muscle mass ratio were used to detect the recovery of motor function. The effect of SalA on repairing pathological injured nerves was evaluated by H&E staining and masson staining, toluidine blue staining and TEM were used to analyze the myelin removal ability. Western blotting and immunohistochemistry were used to identify the expression of NLRP3 inflammasome, autophagy-related proteins and myelin proteins in the injured area. Moreover, the modulatory effects of SalA on cellular antioxidant capacity and damage were investigated by appending the autophagy inhibitor 3-MA based on LPS-treated RSC96 cells. SalA promoted the recovery of motor nerve function after injury, increased the number of myelinated nerve regeneration and improved the damaged myelin sheath structure. SalA administration could increase MBP, NF200 and Beclin-1 expression, reduce the NLRP3/pro-caspase1/ASC signaling pathway in SNI rats, up-regulate LC3 level in RSC96 cells. SalA increased cell survival and decreased inflammatory factors production, which was reversed by 3-MA. SalA restores neuromotor function after nerve crush injury by accelerating early myelin degradation and promoting proliferation. In addition, SalA inhibits neuroinflammation and apoptosis by reducing the activation of NLRP3 inflammasome, and autophagy-related signaling pathways may be potential regulatory targets (graphical abstract).
丹酚酸A（SalA）是丹参中的一种酚酸，具有抗氧化和免疫增强的药用特性。在本研究中，我们研究了SalA对坐骨神经损伤（SNI）大鼠和雪旺细胞神经修复功能及自噬调节的NLRP3炎性小体的作用。构建坐骨神经压迫模型大鼠，采用坐骨神经功能指数和腓肠肌质量比检测运动功能的恢复情况。通过苏木精-伊红（H&E）染色和马松染色评估SalA对病理性损伤神经的修复作用，用甲苯胺蓝染色和透射电子显微镜（TEM）分析髓鞘清除能力。采用蛋白质免疫印迹法和免疫组织化学法鉴定损伤区域NLRP3炎性小体、自噬相关蛋白和髓鞘蛋白的表达。此外，在脂多糖（LPS）处理的RSC96细胞中加入自噬抑制剂3-甲基腺嘌呤（3-MA），研究SalA对细胞抗氧化能力和损伤的调节作用。SalA促进损伤后运动神经功能的恢复，增加有髓神经再生数量，改善受损髓鞘结构。给予SalA可增加髓鞘碱性蛋白（MBP）、神经丝蛋白200（NF200）和Beclin-1的表达，降低SNI大鼠中NLRP3/前半胱天冬酶1/凋亡相关斑点样蛋白（ASC）信号通路，上调RSC96细胞中微管相关蛋白1轻链3（LC3）水平。SalA提高细胞存活率并减少炎性因子产生，3-MA可逆转此作用。SalA通过加速早期髓鞘降解和促进增殖来恢复神经挤压损伤后的神经运动功能。此外，SalA通过降低NLRP3炎性小体的激活来抑制神经炎症和细胞凋亡，自噬相关信号通路可能是潜在的调控靶点（图形摘要）。
