摘要 目的研究蛇床子素通过抑制脊髓背角胞外信号调节激酶(ERK)/丝裂原活化蛋白激酶(MAPK)通路对髓核致炎神经根痛大鼠的保护作用。方法将80只大鼠随机分为对照组(n=20)、模型组(n=20)及低(n=20)、高剂量实验组(n=20)。模型组及低、高剂量实验组大鼠均用手术在特定椎节(L5-6)左侧建立髓核致炎神经根痛大鼠模型。造模后,低、高剂量实验组分别于L_5根周注射20,30 mg·kg-1·d-1蛇床子素,模型组与对照组注射等量生理盐水,连续干预7 d。用Up-Down法检测各组大鼠50%机械性撤足痛阈值(MWT);用酶联免疫吸附(ELISA)法检测血清一氧化氮(NO)、肿瘤坏死因子-α(TNF-α)及白细胞介素-6(IL-6)水平;用苏木精-伊红(HE)染色法观察大鼠脊髓背角组织病理变化;用蛋白质印迹(Wb)法检测脊髓背角磷酸化ERK(p-ERK)与磷酸化p38 MAPK(p-p38 MAPK)蛋白表达。结果对照组、模型组与低、高剂量实验组大鼠术后7 d时的50%MWT分别为24.31±1.79,10.12±1.36,17.33±2.15和26.96±3.11,各组大鼠脊髓背角p-ERK蛋白相对表达量分别为0.14±0.07,0.95±0.05,0.33±0.12和0.25±0.10,p-p38 MAPK蛋白相对表达量分别为0.38±0.11,0.93±0.07,0.69±0.14和0.47±0.09。各组的上述指标相比,差异均有统计学意义(均P<0.05)。结论蛇床子素可改善髓核致炎神经根痛大鼠的痛敏程度,抑制炎性反应,其机制可能与抑制脊髓背角ERK/MAPK通路的信号转导有关。 Objective To investigate the protective effect of osthole on rats with nucleus pulposus-induced radiculopathy by inhibiting the extracellular signal-regulated kinase(ERK)/mitogen-activated protein kinase(MAPK)pathway in the spinal dorsal horn.Methods Eighty SD rats were randomly divided into control group,model group and experimental-L/H groups,with 20 rats in each group.Rats in model group and experimental-L/H groups were operated on the left side of a specific vertebral section(L5-6)to establish a rat model of nucleus pulposus induced by radiculopathy.After modeling,rats in experimental-L/H groups were injected with osthole 20,30 mg·kg-1·d-1 at the L5 root,model group and control group were injected with the same amount of normal saline for 7 d.The 50%mechanical withdrawal pain threshold(MWT)of each group rats was detected by Up-Down method;serum nitric oxide(NO),tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)levels were measured by enzyme-linked immunosorbent assay(ELISA);the pathological changes of rat spinal dorsal horn were observed by hematoxylin-eosin(HE)staining;western blotting(Wb)method was used to detect phosphorylated ERK(p-ERK)and phosphorylated p38 MAPK(p-p38 MAPK)protein expression in spinal dorsal horn.Results In control group,model group and experimental-L/H groups,the 50%MWT at 7 thd after surgery were 24.31±1.79,10.12±1.36,17.33±2.15 and26.96±3.11,the relative expression of p-ERK protein in the spinal dorsal horn were 0.14±0.07,0.95±0.05,0.33±0.12 and 0.25±0.10,the relative expression levels of p-p38 MAPK protein were 0.38±0.11,0.93±0.07,0.69±0.14 and 0.47±0.09.The above indexes were all with significant difference(all P<0.05).Conclusion Osthole can improve the sensitivity of nucleus pulposus-induced radiculopathy rats and inhibit the inflammatory response,and its mechanism may be related to the inhibition of ERK/MAPK pathway signal transduction in the spinal dorsal horn.
机构地区 湖州正博骨科医院骨科
出处 《中国临床药理学杂志》 CAS CSCD 北大核心 2021年第7期855-858,共4页 The Chinese Journal of Clinical Pharmacology
关键词 髓核致炎神经根痛 蛇床子素 脊髓背角 胞外信号调节激酶 丝裂原活化蛋白激酶 nucleus pulposus inflammatory radiculopathy osthole spinal dorsal horn extracellular signal-regulated kinase mitogen-activated protein kinase
分类号 R28 [医药卫生—中药学]
