蛇床子素对髓核致神经根炎性痛大鼠脊髓背角Wnt3a/β-catenin信号通路的影响  

Effect of Osthole on the Wnt3a/β-catenin Signaling Pathway in Spinal Dorsal Horn of Rats with Nucleus Pulposus-Induced Inflammatory Radicular Pain

作　　者：杨琳 张嘉明 何仲贤 刘苑婷 鲁杨 孙来保[3] 江伟航 YANG Lin;ZHANG Jia-Ming;HE Zhong-Xian;LIU Yuan-Ting;LU Yang;SUN Lai-Bao;JIANG Wei-Hang(Guangzhou Panyu Central Hospital,Guangzhou 511400 Guangdong,China;The Sixth Affiliated Hospital,Sun Yat-sen University,Guangzhou 510655 Guangdong,China;The First Affiliated Hospital,Sun Yat-sen University,Guangzhou 510080 Guangdong,China)

机构地区：[1]广州市番禺区中心医院,广东广州511400 [2]中山大学附属第六医院,广东广州1510655 [3]中山大学附属第一医院,广东广州510080

出　　处：《广州中医药大学学报》2023年第1期170-176,共7页Journal of Guangzhou University of Traditional Chinese Medicine

基　　金：广东省中医药局科研项目(编号:20222161);广州市科技计划项目(编号:202102080573);广州市中医药和中西医结合科技项目(编号:20202A010026)。

摘　　要：【目的】探讨蛇床子素对髓核致神经根炎性痛大鼠的治疗作用及机制。【方法】将54只SD大鼠随机分为假手术组、模型组和治疗组,每组18只。模型组和治疗组大鼠构建神经根炎性痛模型,假手术组进行假手术处理。术后2 d,治疗组大鼠经硬膜外注射50μL蛇床子素20 g·L-1,假手术组和模型组大鼠经硬膜外注射相同体积二甲基亚砜(DMSO)。术前3、1 d及术后1、3、7、10、14 d测量大鼠50%机械性撤足阈值(MWT)及热伤害性撤足潜伏期(TWL)。于术后7 d,采用定量聚合酶链反应(Q-PCR)检测术侧脊髓背角Wnt3a、β-catenin mRNA表达水平,采用Western Blot法和免疫荧光染色法分别检测术侧脊髓背角Wnt3a、β-catenin蛋白表达水平,采用酶联免疫吸附分析(ELISA)检测术侧脊髓背角白细胞介素18(IL-18)、肿瘤坏死因子α(TNF-α)水平。【结果】模型组术后各时间点50%MWT及TWL较假手术组降低(P<0.05或P<0.01),术后7 d术侧脊髓背角Wnt3a、β-catenin mRNA和蛋白表达水平及IL-18、TNF-α水平均较假手术组升高(均P<0.01);与模型组比较,治疗组术后3 d出现50%MWT及TWL明显升高(P<0.05或P<0.01),术后7 d术侧脊髓背角Wnt3a、β-catenin mRNA和蛋白表达水平及IL-18、TNF-α水平均降低(P<0.05)。【结论】蛇床子素可有效减轻髓核致炎大鼠神经根痛,其抗炎镇痛机制可能与抑制脊髓背角Wnt3a/β-catenin信号通路,下调IL-18和TNF-α的表达有关。Objective To investigate the therapeutic effect and mechanism of osthole on nucleus pulposus-induced inflammatory radicular pain in rats.Methods Fifty-four SD rats were randomly divided into three groups,including sham-operation group,model group and treatment group,with 18 rats in each group.The inflammatory radicular pain model was constructed for the model group and treatment group,and the sham-operation group was treated with sham surgery.At 2 days postoperatively,20 g·L-1of osthole 50μL was given epidural injection to the treatment group,and the equal volume of dimethyl sulfoxide(DMSO)was given epidural injection to both the sham-operation group and model group.And 50%mechanical withdrawal threshold(MWT)and thermal withdrawal latency(TWL)were measured 3 days and 1 day before surgery and 1,3,7,10 and 14 days after surgery.The mRNA expression levels of Wnt3a andβ-catenin in the operated spinal dorsal horn of were determined by quantitative polymerase chain reaction(Q-PCR)at 7 days postoperatively,and the protein expression levels of Wnt3a andβ-catenin in the operated spinal dorsal horn were detected by Western Blot and immunofluorescence staining,respectively.The levels of interleukin 18(IL-18)and tumor necrosis factorα(TNF-α)were detected in the operated spinal dorsal horn by enzyme-linked immunosorbent assay(ELISA).Results In the model group,50%MWT and TWL were reduced at all postoperative time points compared with the sham-operation group(P<0.05 or P<0.01),and the mRNA and protein expression levels of Wnt3a andβ-catenin and levels of IL-18 and TNF-αin the dorsal horn of the operated spinal cord were significantly increased 7 days after operation compared with the sham-operation group(P<0.01);compared with the model group,50%MWT and TWL of the treatment group were significantly increased 3 days after operation(P<0.05 or P<0.01),and the mRNA and protein expression levels of Wnt3a andβ-catenin and levels of IL-18 and TNF-αin the dorsal horn of the operated spinal cord were significantly decreased 7 d

关 键 词：蛇床子素 神经根炎性痛 Wnt3a/β-catenin信号通路 白细胞介素18 肿瘤坏死因子α 髓核 大鼠 

分 类 号：R285.5[医药卫生—中药学]