Department of Neurosurgery and Jiangxi Key Laboratory of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Department of Neurosurgery and Jiangxi Key Laboratory of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.
World Neurosurg. 2022 Feb;158:e856-e864. doi: 10.1016/j.wneu.2021.11.085. Epub 2021 Nov 24.
Neuroinflammation is an important secondary aggravating factor in spinal cord injury (SCI). Inhibition of the inflammatory response is critical for SCI treatment. Glycyrrhizic acid (GA) is an anti-inflammatory drug, but its utility for SCI is unclear. This study aimed to evaluate the effects of GA on inflammation after SCI and the underlying mechanism.
Cell counting kit-8 assays were performed to assess the viability of highly aggressively proliferating immortalized cells that had been treated with lipopolysaccharide (LPS) and/or GA. Reverse transcription quantitative polymerase chain reaction and Western blotting were performed to assess expression of high mobility group box-1 protein (HMGB1), ionized calcium binding adaptor molecule 1, and inflammatory factors in vitro and in vivo. GA (100 mg/kg) was intraperitoneally injected into rats. Anti-inflammatory effects of GA were analyzed in SCI tissues. p38/Jun N-terminal kinase signaling pathway proteins were analyzed by Western blotting.
Cell counting kit-8 assay results showed that treatment with 100 ng/mL LPS for 12 hours was optimal. After LPS treatment, highly aggressively proliferating immortalized cells were activated; messenger RNA expression levels of HMGB1 and inflammatory factors were increased. GA significantly inhibited LPS-induced HMGB1 expression and inflammatory responses, as determined by reverse transcription quantitative polymerase chain reaction and Western blotting. Transfection with an HMGB1-overexpression plasmid reversed the anti-inflammatory effects of GA. In addition, intraperitoneal injection of GA (100 mg/kg) into rats for 3 days significantly reduced expression levels of HMGB1 and inflammatory factors after SCI in vivo. GA reduced phosphorylation, but not levels, of p38 and Jun N-terminal kinase proteins.
GA attenuates the inflammatory response after SCI by inhibiting HMGB1 through the p38/JNK signaling pathway and thus has therapeutic potential for SCI.
神经炎症是脊髓损伤（SCI）的一个重要的继发性加重因素。抑制炎症反应对 SCI 的治疗至关重要。甘草酸（GA）是一种抗炎药物，但它在 SCI 中的应用尚不清楚。本研究旨在评估 GA 对 SCI 后炎症的影响及其潜在机制。
采用细胞计数试剂盒-8 法检测经脂多糖（LPS）和/或 GA 处理的高度侵袭性增殖的永生化细胞的活力。体外和体内采用逆转录定量聚合酶链反应和 Western blot 法检测高迁移率族蛋白 B1（HMGB1）、离子钙结合衔接分子 1 和炎症因子的表达。GA（100mg/kg）经腹腔注射入大鼠。分析 GA 在 SCI 组织中的抗炎作用。通过 Western blot 分析 p38/Jun N-末端激酶信号通路蛋白。
细胞计数试剂盒-8 检测结果表明，用 100ng/mL LPS 处理 12 小时为最佳。LPS 处理后，高度侵袭性增殖的永生化细胞被激活；HMGB1 和炎症因子的信使 RNA 表达水平增加。GA 显著抑制 LPS 诱导的 HMGB1 表达和炎症反应，逆转录定量聚合酶链反应和 Western blot 检测结果均如此。HMGB1 过表达质粒转染逆转了 GA 的抗炎作用。此外，GA（100mg/kg）腹腔注射大鼠 3 天，体内 SCI 后明显降低 HMGB1 和炎症因子的表达水平。GA 降低了 p38 和 Jun N-末端激酶蛋白的磷酸化水平，但不影响其蛋白水平。
GA 通过 p38/JNK 信号通路抑制 HMGB1 减轻 SCI 后的炎症反应，因此具有治疗 SCI 的潜力。
