摘要
目的:研究人参皂苷Rg3缓解乳腺癌骨转移大鼠痛觉行为的作用及机制。方法:采用大鼠乳腺癌细胞注入胫骨骨髓腔内构建乳腺癌骨转移疼痛模型;随机分成假性手术组、模型组以及人参皂苷Rg3给药组;连续3天静脉注射人参皂苷Rg3;记录大鼠痛觉行为学变化;分子对接分析人参皂苷Rg3与蛋白质的结合;免疫荧光和免疫印迹法检测各组动物脊髓组织炎症相关蛋白表达变化。结果:乳腺癌骨转移可导致骨组织损伤,诱发大鼠机械痛敏、热痛敏及自发痛。同时脊髓胶质细胞和NLRP3炎症小体激活,促炎因子IL-1β表达上调,抗氧化因子Nrf2和GPX4表达下降,线粒体氧化损伤相关蛋白DHODH和细胞色素C表达增加。人参皂苷Rg3给药后,大鼠机械痛、热痛和自发痛缓解,脊髓炎症信号下降,抗氧化Nrf2/GPX4信号增加,线粒体过氧化物信号下降。分子对接显示人参皂苷Rg3可结合Nrf2。结论:人参皂苷Rg3激活Nrf2介导的抗氧化反应,降低脊髓炎症,从而缓解癌痛。
Objective:To investigate the alleviative effect and mechanism of ginsenoside Rg3 on breast cancer-induced bone pain in rats.Methods:A rat model of breast cancer-induced bone pain was constructed by inoculation of MRMT-1 rat breast cancer cells into the medullary cavity of tibia in rats.Rats were randomly divided into three groups,including Sham,Model and ginsenoside Rg3(Rg3)groups.Ginsenoside Rg3 was injected on rats by the tail vein for 3 consecutive days.The changes of pain behavior of rats were detected.Molecular docking analyzed the binding between Rg3 and protein.Immunofluorescence and Western blotting assays were performed to detect the expression of proteins related to inflammation in spinal cord tissue in each group of animals.Results:Bone metastases of breast cancer caused bone damage,induced mechanical pain,thermal hyperalgesia and spontaneous pain of rats.The spinal cord glia cells and NLRP3 inflammasome were activated.The pro-inflammatory factor IL-1β level was increased.The antioxidant factors Nrf2 and GPX4 levels were decreased.The levels of mitochondrial oxidative damage related proteins DHODH and cytochrome C were increased.Ginsenoside Rg3 treatment alleviated the mechanical pain,thermal hyperalgesia and spontaneous pain of rats,inhibited spinal inflammatory reaction,enhanced spinal Nrf2/GPX4-mediated antioxidant responses,decreased spinal mitochondrial oxidative level.In addition,ginsenoside Rg3 combined with Nrf2 assayed by auto-dock.Conclusion:Ginsenoside Rg3 treatment activates Nrf2-mediated antioxidant responses,inhibits inflammatory reaction in the spinal cord,and alleviates cancer-induced bone pain.
作者
李雅晨
盛格格
吴基良
朱海丽
LI Yachen;SHENG Gege;WU Jiliang;ZHU Haili(School of Pharmacy,Xianning Medical College,Hubei University of Science and Technology,Hubei Xianning 437100,China)
出处
《现代肿瘤医学》
CAS
2024年第8期1397-1401,共5页
Journal of Modern Oncology
基金
国家自然科学基金资助项目(编号:81971066)。
关键词
人参皂苷RG3
癌痛
神经炎症
NLRP3炎症小体
线粒体
ginsenoside Rg3
cancer-induced bone pain
spinal inflammation
NLRP3 inflammasome
mitochondria
