Salvianolic Acid A Alleviates Sciatic Nerve Injury in Rats Via Inhibiting NLRP3 Inflammasome Through the Activation of Schwann Cells Autophagy

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Neurochemical Research Pub Date : 2025-04-25 DOI:10.1007/s11064-025-04402-1

Mingfu Fu, Fenghua Zhang, Yanli Song, Jianhang Wang

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Abstract

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).

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丹酚酸A通过激活雪旺细胞自噬抑制NLRP3炎性体减轻大鼠坐骨神经损伤

丹参酚酸A （Salvianolic acid A, SalA）是丹参中的一种酚酸，具有抗氧化和增强免疫的药理作用。在本研究中，我们研究了SalA对坐骨神经损伤（SNI）大鼠和雪旺细胞的神经修复功能和自噬调节的NLRP3炎性体的活性。建立坐骨神经压迫模型大鼠，用坐骨神经功能指数和腓肠肌质量比检测运动功能恢复情况。采用H&；E染色和马松染色评价SalA对病理性损伤神经的修复作用，甲苯胺蓝染色和透射电镜分析SalA对髓磷脂的去除能力。Western blotting和免疫组化检测损伤区NLRP3炎性体、自噬相关蛋白和髓磷脂蛋白的表达。此外，通过在lps处理的RSC96细胞中添加自噬抑制剂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恢复，增加有髓神经再生数量，改善受损髓鞘结构。SalA可增加SNI大鼠MBP、NF200、Beclin-1表达，降低NLRP3/ procaspase1 /ASC信号通路，上调RSC96细胞LC3水平。SalA增加了细胞存活率，减少了炎症因子的产生，而3-MA可以逆转这一过程。SalA通过加速早期髓磷脂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炎性体的激活来抑制神经炎症和细胞凋亡，自噬相关的信号通路可能是潜在的调控靶点（图形摘要）。

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来源期刊

Neurochemical Research 医学-神经科学

CiteScore

7.70

自引率

2.30%

发文量

320

审稿时长

6 months

期刊介绍： Neurochemical Research is devoted to the rapid publication of studies that use neurochemical methodology in research on nervous system structure and function. The journal publishes original reports of experimental and clinical research results, perceptive reviews of significant problem areas in the neurosciences, brief comments of a methodological or interpretive nature, and research summaries conducted by leading scientists whose works are not readily available in English.