NF-κB通过激活MKK4-JNK-c-Jun通路介导大鼠腰椎间盘髓核突出引起的疼痛反应

Nuclear factor-KB mediates the painful response induced by nucleus pulposus herniation of lumbar disc intervertebral by activating the MKK4-JNK-c-Jun pathway in rats

目的探讨核因子-κB(NF-κB)能否通过激活MKK4-JNK-c-Jun通路介导大鼠腰椎间盘髓核突出诱导的疼痛反应。方法应用SD成年雄性大鼠建立腰椎间盘髓核突出引起的疼痛模型。应用热痛测试方法检测大鼠热痛阈值。应用Western blot法测定大鼠脊髓磷酸化(p)MKK4(p-MKK4)、p-JNK及p-c-Jun的表达水平。结果腰椎间盘髓核突出引起大鼠出现热痛阈降低(疼痛反应)。腹腔注射NF-KB抑制剂(PDTC)明显地抑制髓核突出引起的疼痛反应;另外,PDTC也能明显地拮抗髓核突出对脊髓p-MKK4、p-JNK及p-c-Jun表达的上调作用。结论 NF-κB通过激活MKK4-JNK-c-Jun通路介导腰椎间盘髓核突出引起的疼痛反应。

Objective To explore whether Nuclear factor-KB(NF-KB)mediates the painful response induced by nucleus pulposus herniation of lumbar disc intervertebral by activating the mitogen-activated protein kinases kinases 4(MKK4)-c-Jun-N-terminal kinase(JNK)-c-Jun pathway. Methods A model of painful response induced by nucleus pulposus herniation of lumbar intervertebral disk was established in male Sprague-Dawley(SD)rats. The heat pain threshold was examined by the heat pain testing apparatus. The expression levels of the spinal phorsphorylated(p)-MKK4,p-JNK and p-c-Jun were tested by western blot assay.Results The heat painful threshold(painful response)was reduced in rats with nucleus pulposus herniation of lumbar intervertebral disk. Intraperitoneal injection of PDTC,an inhibitor of NF-KB,markedly inhibited the nucleus pulposus herniation-induced painful responses. Furthermore,PDTC also obviously reduced the nucleus pulposus herniation-induced upregulation of the expression levels of p-MKK4,p-JNK and p-c-Jun. Conclusion NF-KB mediates the painful response induced by the nucleus pulposus herniation of lumbar intervertebral disk by activating the MKK4-JNK-c-Jun pathway in rats.