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补阳还五汤抑制大鼠脊髓损伤后铁死亡和促进神经修复的作用机制研究

Research on mechanism of Buyang Huanwu decoction in inhibiting ferroptosis and promoting nerve repair after spinal cord injury in rats

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【作者】 郭晓辉卜保献钱煜昊李艳侠卜献忠李寒曦郝宇鹏

【Author】 GUO Xiao-hui;BU Bao-xian;QIAN Yu-hao;LI Yan-xia;BU Xian-zhong;LI Han-xi;HAO Yu-Peng;Spinal Surgery Diagnosis and Treatment Center,Henan Provincial Luoyang Orthopedic Hospital(Henan Provincial Orthopedic Hospital);Orthopedic Injury Diagnosis and Treatment Center,the First Affiliated Hospital of Henan University of Chinese Medicine;

【通讯作者】 卜保献;

【机构】 河南省洛阳正骨医院(河南省骨科医院)脊柱外科诊疗中心河南中医药大学第一附属医院骨伤诊疗中心

【摘要】 目的 本研究旨在探讨补阳还五汤(Buyang Huanwu decoction,BYHWD)抑制铁死亡、促进神经修复的作用及机制。方法 将48只SD大鼠随机分为假手术组、模型组、莱菔硫烷(sulforaphane,SFN)组和BYHWD组。采用改良Allen’s法建立T9~T10节段脊髓损伤(spinal cord injury,SCI)模型。SFN组给予莱菔硫烷,BYHWD组灌胃给予补阳还五汤水煎剂。于造模后3 d、7 d评估斜板试验运动功能; ELISA法检测血清铁及脊髓组织谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)含量;免疫组化检测脊髓损伤区生长相关蛋白43(growth-associated protein 43,GAP-43)、神经丝蛋白200(neurofilament 200,NF200)表达; RT-q PCR检测核因子E2相关因子2(nuclear factor erythroid 2-related factor 2,Nrf2)、血红素氧合酶-1(heme oxygenase-1,HO-1) mRNA表达。结果 与模型组相比,BYHWD组和SFN组大鼠斜板试验角度显著增加(P<0.05),血清铁水平显著降低(P<0.05),脊髓GPX4含量显著升高(P<0.05),GAP-43和NF200阳性细胞数显著增多(P<0.05),且脊髓Nrf2、HO-1 mRNA表达显著上调(P<0.05); BYHWD组疗效与SFN组相当(P > 0.05)。结论 补阳还五汤可有效改善SCI大鼠运动功能,其机制可能与激活Nrf2/HO-1通路,上调GPX4表达,抑制铁死亡(降低血清铁),同时促进神经修复(增加GAP-43、NF200表达)有关。

【Abstract】 Objective To investigate the effects and mechanisms of Buyang Huanwu decoction( BYHWD) in inhibiting ferroptosis and promoting neural repair. Methods A total of forty-eight SD rats were randomly divided into sham-operated group,model group,sulforaphane( SFN) group and BYHWD group. A spinal cord injury( SCI) model at the T9-T10 segment was established using the modified Allen’s method. The SFN group received sulforaphane,while the BYHWD group administered BYHWD aqueous extract by intragastric gavage. Motor function was assessed using the inclined plane test at 3 and 7 days post-injury. Serum iron levels and glutathione peroxidase 4( GPX4) content in spinal cord tissue were measured by ELISA. Immunohistochemistry was used to detect expression of growth-associated protein 43( GAP-43) and neurofilament 200( NF200) in the spinal cord lesion area. RT-qPCR was used to quantify mRNA expression of nuclear factor erythroid 2-related factor 2( Nrf2) and heme oxygenase-1( HO-1).Results Compared with the model group,both BYHWD and SFN groups showed significantly increased inclined plane angles( P < 0. 05),significantly decreased serum iron levels( P < 0. 05),and significantly increased cord GPX4 content( P < 0. 05). Furthermore,these groups exhibited significantly greater numbers of GAP-43 and NF200-positive cells( P < 0. 05),alongside upregulated spinal cord Nrf2 and HO-1 mRNA expression( P < 0. 05). The therapeutic efficacy of BYHWD group was comparable to that of SFN group( P > 0. 05). Conclusion Buyang Huanwu decoction effectively improves motor function in SCI rats. Its neuroprotective mechanism likely involves activation of the Nrf2/HO-1 pathway,upregulation of GPX4 expression,inhibition of ferroptosis( reducing serum iron),and promotion of neural repair( increasing GAP-43 and NF200 expression).

【基金】 洛阳市2022—2024年度中医重点学科资助项目(洛卫科教[2022]5号)
  • 【文献出处】 医药论坛杂志 ,Journal of Medical Forum , 编辑部邮箱 ,2026年09期
  • 【分类号】R285.5
  • 【下载频次】65
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