浙江中西医结合杂志

王凤双,汤敏,金亚玲,陈立辉,蒋晓双,林九洲,陈卫挺.Purmorphamine联合甲泼尼龙对大鼠脊髓损伤后脊髓的保护作用[J].浙江中西医结合杂志,2026,36(3):

Purmorphamine联合甲泼尼龙对大鼠脊髓损伤后脊髓的保护作用

Neuroprotective Effects of Purmorphamine Combined with Methylprednisolone on Spinal Cord Injury in Rats

投稿时间：2025-09-15 修订日期：2026-01-07

DOI：

中文关键词: 脊髓损伤 Purmorphamine 甲泼尼龙 Hedgehog信号通路炎症氧化应激神经保护

英文关键词:Spinal cord injury Purmorphamine Methylprednisolone Hedgehog signaling pathway Inflammation Oxidative stress Neuroprotection

基金项目:浙江省自然科学基金资助项目(LTGY24H150007)；浙江省医药卫生科技计划资助项目(2024KY555)

作者	单位	E-mail
王凤双	台州市中西医结合医院	583414991@qq.com
汤敏
金亚玲
陈立辉
蒋晓双
林九洲
陈卫挺^*	临海市第一人民医院	chenweitingtz@163.com

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中文摘要:

目的：脊髓损伤（spinal cord injury, SCI）是一种严重疾病，常导致显著残疾，亟需开发有效的神经保护策略。本研究旨在探讨Hedgehog信号通路激动剂Purmorphamine联合甲泼尼龙（methylprednisolone，MP）对SCI的神经保护作用及其潜在机制。方法：建立SD大鼠SCI模型，随机分为对照组、模型组、Purmorphamine组（10 mg/kg）、低剂量MP组（20 mg/kg）、高剂量MP组（30 mg/kg）及Purmorphamine联合低剂量MP组（10 mg/kg Purmorphamine + 20 mg/kg MP），每组6只，连续给药7天。通过Reuter评分、苏木精-伊红染色（HE）染色、末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记法（TUNEL）染色、酶联免疫吸附试验（ELISA）、氧化应激指标检测及蛋白印迹（Western Blot，WB）等方法，评估各组大鼠的神经功能、组织学改变、炎症反应、氧化应激水平及Caspase-3蛋白表达。结果：与模型组相比，Purmorphamine联合低剂量MP组Reuter评分[11.00±0.00比7.17±1.47，P＜0.01]、白细胞介素-1β（IL-1β）[(437.9±81.4)pg/ml比(203.1±75.3)pg/ml，P＜0.01]、肿瘤坏死因子α（TNF-α）[(139.0±32.3)pg/ml比(58.1±20.2)pg/ml，P＜0.01]、丙二醛（MDA）[(17.5±4.23)nmol/mg比(10.0±4.5)nmol/mg，P＜0.01]、凋亡指数[(39.09±13.61)%比(27.63±8.79)%，P<0.01]、Caspase-3蛋白表达下调，白细胞介素-10（IL-10）[(239.6±76.9)pg/ml比(443.1±70.6)pg/ml，P＜0.01]、超氧化物歧化酶（SOD）[(83.6±28.3)U/mg比(190.2±35.5)U/mg，P＜0.01]表达上调。与低剂量MP组相比，联合组Reuter评分[9.00±0.89比7.17±1.47，P＜0.05]、IL-1β[(323.3±52.7)pg/ml比(203.1±75.3)pg/ml，P＜0.05]、TNF-α[(94.0±33.6)pg/ml比(58.1±20.2)pg/ml，P＜0.05]、MDA[(15.1±6.7)比(10.0±4.5)nmmol/mg，P＜0.05]、凋亡指数[(36.42±11.59)%比(27.63±8.79)%，P＜0.05]、Caspase-3蛋白表达下调，IL-10[(401.4±106.4)pg/ml比(443.1±70.6)pg/ml，P＜0.05]、SOD[(178.4±31.4)U/mg比(190.2±35.5)U/mg，P＜0.01]表达上调。结论：Purmorphamine联合MP通过抗炎、抗氧化及抗凋亡机制发挥协同神经保护作用，联合治疗优于单药干预，为SCI治疗提供新策略，具有潜在临床应用价值。

英文摘要:

Objective: Spinal cord injury (SCI) is a severe condition often associated with significant disability, highlighting the urgent need to explore effective neuroprotective strategies. This study aimed to investigate the neuroprotective effects and underlying mechanisms of the Hedgehog pathway agonist Purmorphamine combined with methylprednisolone (MP) in a rat model of SCI. Methods: A rat SCI model was established and divided into six groups: Sham group, SCI model group, Purmorphamine group (10 mg/kg), low-dose MP group (20 mg/kg), high-dose MP group (30 mg/kg), and combination group (10 mg/kg Purmorphamine + 20 mg/kg MP). All treatments were administered for seven consecutive days. Neurological function and pathophysiological changes were assessed using Reuter scores, hematoxylin and eosin (HE) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, enzyme-linked immunosorbent assay (ELISA), oxidative stress marker assays, and Western blot (WB) analysis of Caspase-3 protein expression. Results: Compared with the model group, the combination group showed significantly improved Reuter scores [11.00±0.00 vs. 7.17±1.47, P<0.01], and decreased levels of proinflammatory cytokines IL-1β [(437.9±81.4)pg/ml vs. (203.1±75.3)pg/ml, P<0.01], TNF-α [(139.0±32.3)pg/ml vs. (58.1±20.2)pg/ml, P<0.01], malondialdehyde (MDA) [(17.5±4.23)nmol/mg vs. (10.0±4.5)nmol/mg, P<0.01], and apoptotic index [(39.09±13.61)% vs. (27.63±8.79)%, P<0.01], along with downregulated Caspase-3 expression. In contrast, anti-inflammatory cytokine IL-10 [(239.6±76.9)pg/ml vs. (443.1±70.6)pg/ml, P<0.01] and antioxidant enzyme superoxide dismutase (SOD) [(83.6±28.3)U/mg vs. (190.2±35.5)U/mg, P<0.01] were significantly upregulated. Compared with the low-dose MP group, the combination group further improved Reuter scores [9.00±0.89 vs. 7.17±1.47, P<0.05], and significantly reduced IL-1β [(323.3±52.7)pg/ml vs. (203.1±75.3)pg/ml, P<0.05], TNF-α [(94.0±33.6)pg/ml vs. (58.1±20.2)pg/ml, P<0.05], MDA [(15.1±6.7)nmol/mg vs. (10.0±4.5)nmol/mg, P<0.05], and apoptotic index [(36.42±11.59)% vs. (27.63±8.79)%, P<0.05], with enhanced downregulation of Caspase-3 and upregulation of IL-10 [(401.4±106.4)pg/ml vs. (443.1±70.6)pg/ml, P<0.05] and SOD [(178.4±31.4)U/mg vs. (190.2±35.5)U/mg, P<0.01]. Conclusion: Purmorphamine combined with MP exerts synergistic neuroprotective effects after SCI through anti-inflammatory, antioxidant, and anti-apoptotic mechanisms. These findings provide new insight into SCI therapy and suggest potential clinical applications.

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