大黄素对骨关节炎模型小鼠痛觉行为的调节机制  

Mechanism of emodin modulating pain behavior in mouse model of osteoarthritis

作　　者：袁满 冯子瀚 谢敏 王柏军 YUAN Man;FENG Zihan;XIE Min;WANG Bojun(School of Pharmacy,Hubei University of Science and Technology,Xianning 437100,China)

机构地区：[1]湖北科技学院药学院,437100

出　　处：《天津医药》2024年第6期572-577,共6页Tianjin Medical Journal

基　　金：国家自然科学基金青年基金项目(81901149);湖北省自然科学基金资助项目(2022CFB356)。

摘　　要：目的基于线粒体关键基因探究大黄素缓解骨关节炎模型小鼠痛觉行为的作用机制。方法30只C57BL/6J小鼠随机分为对照组、骨关节炎(OA)组和OA+大黄素组,每组10只。OA组和OA+大黄素组进行膝关节内注入完全弗氏佐剂(20μL)建立OA模型,OA+大黄素组进行大黄素腹腔内给药(10 mg/kg)。行为学测试后,收集小鼠膝关节组织进行苏木素-伊红(HE)染色。蛋白免疫印迹分析膝关节组织炎性因子白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)以及线粒体相关蛋白NADH脱氢酶(泛醌)黄素蛋白1(NDUFV1)、细胞色素C氧化酶亚基5B(COX5B)、细胞色素C氧化酶15(COX15)、NADH脱氢酶(泛醌)1α亚复合物亚基10(NDUFA10)的表达水平。结果与对照组相比,OA组小鼠机械痛阈值降低,转棒停留时间和运动距离下降(P<0.05);与OA组相比,OA+大黄素组机械痛阈值升高,转棒停留时间和运动距离均增加(P<0.05)。对照组膝关节关节软骨和软骨下骨结构完整,OA组软骨层变薄,软骨下小梁退化,大黄素处理缓解了软骨变性。与对照组相比,OA组IL-1β、TNF-α、COX15和NDUFA10表达升高,NDUFV1和COX5B表达降低,大黄素处理可恢复上述蛋白表达水平(P<0.05)。结论大黄素可通过调控炎性因子和线粒体相关蛋白的表达来缓解OA小鼠痛觉行为。Objective To explore the regulatory mechanism of emodin on pain behavior in a mouse model of osteoarthritis based on mitochondrial key genes.Methods Thirty C57BL/6J mice were randomly divided into the control group,the osteoarthritis(OA)model group and the emodin-treated(OA+emodin)group,10 mice per each group.The mice in the OA group and the OA+emodin group were intra-articular injection of complete Freund’s adjuvant(20μL)in knee to establish the OA model,and mice in the OA+emodin group were treated by intraperitoneal emodin(10 mg/kg)injection.After behavioral testing,knee tissue of mice was collected for hematoxylin-eosin staining.Western blot analysis was used to detect expression levels of proinflammatory factors interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and mitochondria-related proteins NADH dehydrogenase(ubiquinone)flavoprotein 1(NDUFV1),cytochrome C oxidase subunit 5B(COX5B),cytochrome C oxidase assembly protein COX15 homolog(COX15),NADH dehydrogenase(ubiquinone)1 alpha subcomplex subunit 10(NDUFA10)in knee tissue.Results Compared with the control group,mice in the OA group showed decreased mechanical nociceptive threshold(PWT),reduced latency and distance in rotarod test(P<0.05).Compared with the OA group,mice in the OA+emodin group showed increased PWT,latency,and distance(P<0.05).In the control group,the structures of cartilage and subchondral bone were intact,while in the OA group,the cartilage was thinner and the subchondral trabeculae was deteriorated.The treatment with emodin alleviated cartilage degeneration.The expression levels of IL-1β,TNF-α,COX15 and NDUFA10 were increased while expression levels of NDUFV1 and COX5B were decreased in the OA group compared with the control group.The emodin treatment restored the above-mentioned protein expression levels(P<0.05).Conclusion Emodin can alleviate pain behavior in OA mice by regulating the expressions of inflammatory factors and mitochondrial related proteins.

关 键 词：骨关节炎 大黄素 线粒体 计算生物学 炎症性疼痛 

分 类 号：R965.1[医药卫生—药理学] R684.3[医药卫生—药学]