基于c-JNK/CXCL1信号通路研究椎间盘丸对腰椎间盘突出症大鼠脊髓炎症的抑制作用  

The Inhibitory Effect of Zhuijianpan Pills on Spinal Cord Inflammation in Rats with Lumbar Disc Herniation Based on c-JNK/CXCL1 Signaling Pathway

作　　者：牛辉 鲍朝辉 张文明 高乾坤 周献伟[1] 杨洸[1] 刘鸣[2] NIU Hui;BAO Chaohui;ZHANG Wenming;GAO Qiankun;ZHOU Xianwei;YANG Guang;LIU Ming(The Third Department of Spine Surgery,Luoyang Orthopedic Hospital of Henan Province,Zhengzhou 450009 Henan,China;Department of Orthopedics,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450000 Henan,China)

机构地区：[1]河南省洛阳正骨医院脊柱外三科,河南郑州450009 [2]郑州大学第一附属医院骨科,河南郑州450000

出　　处：《中药新药与临床药理》2021年第5期655-660,共6页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：河南省中医药科学研究专项课题(2018ZY2022);河南省医学科技攻关计划项目(LHGJ20190178)。

摘　　要：目的观察椎间盘丸对腰椎间盘突出症大鼠脊髓炎症的抑制作用,并探讨其通过c-Jun氨基末端激酶(c-JNK)/趋化因子配体1(CXCL1)信号通路的作用机制。方法将85只大鼠随机选取70只建立腰椎间盘突出症大鼠模型。将模型复制成功的60只大鼠随机分为模型组,椎间盘丸低、高剂量组,阳性对照组,每组15只;剩余15只为假手术组。模型复制2 h后,椎间盘丸低、高剂量组和阳性对照组分别灌胃1.85、3.70 g·kg^(-1)椎间盘丸溶液和0.77 mg·kg^(-1)美洛昔康溶液,假手术组和模型组灌胃生理盐水。干预7 d后,观察实验大鼠的一般情况,测定痛反应阈值,酶联免疫吸附法(ELISA)测定脊髓背角组织白细胞介素6(IL-6)、白细胞介素1β(IL-1β)水平,HE染色观察大鼠背根神经节组织病理学变化,Western Blot法检测脊髓背角组织离子钙接头蛋白(Iba-1)、c-JNK、p-c-JNK、CXCL1蛋白相对表达水平。结果与假手术组比较,模型组干预1 d与7 d痛阈明显升高,差异有统计学意义(P<0.01);与模型组比较,椎间盘丸低、高剂量组和阳性对照组干预1 d与7 d痛阈均明显降低,差异有统计学意义(P<0.01)。与假手术组比较,模型组IL-6、IL-1β水平均明显升高,差异有统计学意义(P<0.01);与模型组比较,椎间盘丸低、高剂量组和阳性对照组IL-6、IL-1β水平均降低,差异有统计学意义(P<0.05,P<0.01)。假手术组大鼠背根神经节中神经元细胞核位于中央,核仁清晰,胞质内有排列均匀的颗粒状物尼氏小体,无细胞肿胀及炎性细胞浸润;模型组大鼠背根神经节中神经元细胞核不规则,核仁不清晰,胞质中尼氏小体排列不均匀,细胞明显肿胀,神经元细胞胞浆呈空泡样变化;椎间盘丸低、高剂量组和阳性对照组有所改善。与假手术组比较,模型组Iba-1、p-c-JNK、CXCL1蛋白相对表达水平均明显升高(P<0.01);与模型组比较,椎间盘丸低、高剂量组和阳性对照组Iba-1、p-c-JNK、CXCL1�Objective To observe the inhibitory effect of Zhuijianpan pills on spinal cord inflammation in rats with lumbar disc herniation,and to explore its mechanism of action through the c-Jun N-terminal kinase(c-JNK)/chemokine(C-X-X motif)ligand 1(CXCL1)signaling pathway.MethodsSeventy rats were randomly selected from85 rats to establish a lumbar disc herniation rat model.60 rats were successfully modeled and randomly divided into model group,low-dose group,high-dose group,and positive control group.Each group included 15 rats,the remaining 15 rats were assigned to sham operation group.Two hours after modeling,low-dose group,high-dose group and positive control group were intragastrically administered with 1.85,3.70 g·kg^(-1)Zhuijianpan pills solution and 0.77 mg·kg^(-1)meloxicam solution,respectively.The sham operation group and model group were given normal saline.After 7 days of intervention,we observed the general conditions of the experimental rats and measured the pain threshold.The levels of IL-6 and IL-1βin the spinal dorsal horn tissue were measured by ELISA.HE staining was used to observe the histopathological changes of rat dorsal root ganglia,and western blot was also applied to detect the relative expression levels of Iba-1,c-JNK,p-c-JNK,and CXCL1 proteins in the spinal dorsal horn tissue.ResultsCompared with the sham operation group,the pain threshold of the model group at 1st,7th day after intervention obviously increased and with a statistically significant difference(P<0.01).Compared with the model group,the pain threshold of the low-dose group,high-dose group and positive control group at 1st,7th day after intervention obviously reduced and with a statistically significant difference(P<0.01).Compared with the sham operation group,the IL-6 and IL-1βlevels of the model group were increased,and the difference was statistically significant(P<0.01).Compared with the model group,the levels of IL-6 and IL-1βin the low-dose group,high-dose group and positive control group were decreased,and the difference

关 键 词：腰椎间盘突出症 椎间盘丸 脊髓炎症 c-Jun氨基末端激酶/趋化因子配体1(c-JNK/CXCL1)信号通路 大鼠 

分 类 号：R285.5[医药卫生—中药学]