Department of spinal surgery, Jining First People's Hospital, Jining, People's Republic of China.
J Spinal Cord Med. 2024 Sep;47(5):669-680. doi: 10.1080/10790268.2023.2183329. Epub 2023 Mar 13.
CONTEXT/OBJECTIVE: This study aimed to explore the anti-inflammatory and neuroprotective effects of protocatechuic aldehyde (PCA) in rats with spinal cord injury (SCI) and to clarify the molecular mechanisms underlying its pharmacological effects.
Male Sprague Dawley rat model of moderate spinal cord contusion were established.
Third-class first-class hospital.
The Basso, Beattie, and Bresnahan scores and performance on the inclined plane test were evaluated. Histological analyses were performed via hematoxylin and eosin staining. Apoptosis in the spinal cord and neurons was detected by 5 terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling staining. Apoptotic factors (Bax, Bcl-2, and cleaved caspase-3) were also evaluated. INOS, IL-1β, IL-10, TNF-α, Wnt-3α, β-catenin, iBA-1, and NeuN were assessed by real-time reverse transcription-polymerase chain reaction (RT-PCR), western blotting (WB), and enzyme-linked immunosorbent assay. Cell viability and the immunofluorescence of IL-1β were measured in PC-12 cells.
Using WB and quantitative reverse transcription-PCR, we confirmed that PCA treatment activated the Wnt/β-catenin signaling axis in vivo and in vitro. Hematoxylin and eosin staining and hindlimb motor functional evaluation revealed that treatment with PCA improved tissue protection and functional recovery via the Wnt/β-catenin axis. The upregulation of TUNEL-positive cells, downregulation of neurons, elevated apoptosis-associated factors in rats, and increased apoptotic rates were observed in microglia and PC-12 after PCA application. Finally, PCA mitigated SCI-induced inflammation by targeting the Wnt/β-catenin axis.
This study provided preliminary evidence that PCA inhibits neuroinflammation and apoptosis through the Wnt/β-catenin pathway, thereby attenuating the secondary injury after SCI and promoting the regeneration of injured spinal tissues.
背景/目的：本研究旨在探讨原儿茶醛（PCA）对大鼠脊髓损伤（SCI）的抗炎和神经保护作用，并阐明其药理作用的分子机制。
建立雄性 Sprague Dawley 大鼠中度脊髓挫伤模型。
三级甲等医院。
通过 Basso、Beattie 和 Bresnahan 评分以及斜板试验评估大鼠的运动功能。采用苏木精-伊红（H&E）染色进行组织学分析。通过末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记（TUNEL）染色检测脊髓和神经元的凋亡。还评估了凋亡因子（Bax、Bcl-2 和 cleaved caspase-3）。通过实时逆转录聚合酶链反应（RT-PCR）、Western blot（WB）和酶联免疫吸附试验（ELISA）检测 INOS、IL-1β、IL-10、TNF-α、Wnt-3α、β-catenin、iBA-1 和 NeuN。通过细胞活力和 IL-1β 的免疫荧光检测 PC-12 细胞。
通过 WB 和定量 RT-PCR，我们证实 PCA 治疗在体内和体外激活了 Wnt/β-catenin 信号通路。H&E 染色和后肢运动功能评估表明，通过 Wnt/β-catenin 轴，PCA 治疗改善了组织保护和功能恢复。PCA 处理后，大鼠的 TUNEL 阳性细胞上调、神经元下调、凋亡相关因子升高以及小胶质细胞和 PC-12 中的凋亡率升高。最后，PCA 通过靶向 Wnt/β-catenin 轴减轻 SCI 诱导的炎症。
本研究初步证明 PCA 通过 Wnt/β-catenin 通路抑制神经炎症和细胞凋亡，从而减轻 SCI 后的继发性损伤，促进损伤脊髓组织的再生。
