载梓醇壳聚糖-柠檬酸水凝胶：一种新的脊髓损伤治疗策略

IF 3.4 4区医学 Q2 CLINICAL NEUROLOGY

Journal of Neurorestoratology Pub Date : 2025-06-28 DOI:10.1016/j.jnrt.2025.100228

Dapeng Zhao , Hengrui Li , Xiaoyu Wang , Ailing Yu , Lanhua Li , Baoliang Sun , Ying Wang , Guojun Wang , Jingyi Sun

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引用次数: 0

摘要

脊髓损伤（SCI）通常由创伤性事件引起，可导致神经损伤、感觉和运动功能受损，并可能对生命构成严重威胁。持续炎症引起的继发性损伤机制破坏局部微环境，导致神经元细胞死亡，阻碍神经再生。本研究采用壳聚糖-柠檬酸（CS-CA）水凝胶作为梓醇（CAT-CS-CA）的载体，直接应用于损伤部位促进SCI修复。方法对scat -CS-CA和CS-CA水凝胶进行表征并植入大鼠脊髓损伤模型。实验采用雄性Sprague-Dawley大鼠54只（230 ~ 250 g）。将6只大鼠随机分为两组（每组3只）进行水凝胶的体内降解。48只大鼠按随机化方案随机分为4组（n = 12）：假手术组（仅椎板切除术）、SCI组、CS-CA水凝胶组和CAT-CS-CA水凝胶组。每组随机抽取3只大鼠进行血清和脊髓组织提取，采用ELISA和RT-qPCR检测各组大鼠血清中各种炎症因子（IL-1β、IL-6、TNF-α、IL-10）的表达水平。随机选取3只大鼠进行后肢运动功能评价。各组其余6只大鼠分别检测神经元核（NeuN）、β iii -微管蛋白（Tuj1）、胶质纤维酸性蛋白（GFAP）和巨噬细胞极化（M1/M2标记物）的表达。结果CAT-CS-CA水凝胶保留了CS-CA水凝胶的优点，增强了神经保护和抗炎能力。在损伤大鼠脊髓内植入CAT-CS-CA，增强了神经元存活，刺激了轴突再生，并显著抑制了损伤部位的胶质细胞增殖。促进巨噬细胞向M2表型极化，显著增强脊髓损伤大鼠后肢运动功能。结论cat - cs - ca水凝胶可促进神经元存活，抑制神经胶质瘢痕形成，改善运动功能，是一种有前景的脊髓损伤修复策略。

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Chitosan-citric acid hydrogels loaded with catalpol: A novel therapeutic strategy for spinal cord injury

Background

Spinal cord injury (SCI), which often results from traumatic incidents, leads to neural damage and impaired sensory and motor functions and may pose a serious threat to life. Secondary injury mechanisms caused by persistent inflammation disrupt the local microenvironment, causing neuronal cell death and hindering neural regeneration. This study used a chitosan-citric acid (CS-CA) hydrogel as a carrier for Catalpol (CAT-CS-CA), which was directly applied to the injury site to promote SCI repair.

Methods

CAT-CS-CA and CS-CA hydrogels were characterized and implanted into rat SCI models. Fifty-four male Sprague-Dawley rats (230–250 g) rats were involved in the experiment. Six rats were randomly divided into two groups (n = 3 per group) for in vivo degradation of hydrogels. Forty-eight rats were randomly assigned into four groups (n = 12) using a randomization protocol: sham operation group (laminectomy only), SCI group, CS-CA hydrogel group, and CAT-CS-CA hydrogel group. From each group, 3 rats were randomly selected for serum and spinal cord tissue extraction, followed by ELISA and RT-qPCR assays to determine the expression levels of various inflammatory factors (IL-1β, IL-6, TNF-α, and IL-10). Another 3 randomly selected rats were used for the evaluation of hindlimb motor function. The remaining 6 rats in each group were used to detect the expression of neuronal nuclei (NeuN), βIII-tubulin (Tuj1), glial fibrillary acidic protein (GFAP), and macrophage polarization (M1/M2 markers).

Results

The CAT-CS-CA hydrogel retains CS-CA hydrogel's advantages and gains enhanced neuroprotective and anti-inflammatory abilities. The implantation of CAT-CS-CA into injured rat spinal cords enhanced neuronal survival, stimulated axonal regeneration, and significantly suppressed glial proliferation at the injury site. In addition, it promoted macrophage polarization to the M2 phenotype and substantially enhanced hindlimb motor function in rats with SCI.