Abstract：
Pro-inflammatory macrophages (M1-polarized) play a crucial role in neuroinflammation and neuropathic pain following nerve injury. Redirecting macrophage polarization toward anti-inflammatory (M2-polarized) phenotypes offers a promising therapeutic strategy. Recognized for their anti-inflammatory and immunomodulatory properties, probiotics are becoming a focal point of research. This study investigated the effects of Lactobacillus plantarum on macrophage polarization, nerve protection, and neuropathic pain behavior following chronic constriction injury (CCI) of the median nerve. Rats received daily oral doses of L. plantarum for 28 days before and 14 days after CCI. Subsequently, behavioral and electrophysiological assessments were performed. The M1 marker CD86 levels, M2 marker CD206 levels, and concentrations of pro-inflammatory and anti-inflammatory cytokines in the injured median nerve were assessed. L. plantarum administration effectively reduced neuropathic pain behavior and the Firmicutes to Bacteroidetes ratio after CCI. Moreover, L. plantarum treatment increased serum short-chain fatty acids (SCFAs) levels, preserved myelination of the injured median nerve, and suppressed injury-induced discharges. In CCI rats treated with L. plantarum, there was a reduction in CD86 and pro-inflammatory cytokine levels, accompanied by an increase in CD206 and the release of anti-inflammatory cytokines. Furthermore, receptors for anti-inflammatory cytokines were localized on Schwann cells, and their expression was significantly upregulated in the injured nerves of CCI rats receiving L. plantarum. In conclusion, L. plantarum shifts macrophage phenotypes from M1 to M2 by promoting the production of SCFAs and enhancing the release of anti-inflammatory cytokines. Ultimately, this process preserves nerve fiber integrity and impedes the onset of neuropathic pain.
摘要：
促炎巨噬细胞（M1极化）在神经损伤后的神经炎症和神经性疼痛中起关键作用。将巨噬细胞极化重定向到抗炎（M2极化）表型提供了有希望的治疗策略。公认的抗炎和免疫调节特性，益生菌正成为研究的焦点。本研究探讨了植物乳杆菌对巨噬细胞极化的影响,神经保护,和慢性正中神经压迫性损伤（CCI）后的神经性疼痛行为。CCI前28天和CCI后14天，大鼠每日口服植物乳杆菌。随后，进行行为和电生理评估.M1标记CD86水平，M2标记CD206水平，评估受损正中神经中促炎和抗炎细胞因子的浓度。植物乳杆菌的给药有效地降低了CCI后的神经性疼痛行为和Firmicutes与拟杆菌的比率。此外，植物乳杆菌治疗增加血清短链脂肪酸（SCFA）水平，保留了受损正中神经的髓鞘形成，并抑制损伤引起的放电。在用植物乳杆菌治疗的CCI大鼠中，CD86和促炎细胞因子水平降低，伴随着CD206的增加和抗炎细胞因子的释放。此外，抗炎细胞因子的受体定位于施万细胞上，它们在接受植物乳杆菌的CCI大鼠受损神经中的表达显着上调。总之,植物乳杆菌通过促进SCFA的产生和增强抗炎细胞因子的释放将巨噬细胞表型从M1转移到M2。最终,该过程保留了神经纤维的完整性并阻止了神经性疼痛的发作。
