{"title":"在颈椎间盘退变大鼠模型中,电针通过 IL-22/JAK2-STAT3 信号通路改善髓核细胞凋亡","authors":"Sen Yan, Ling-Yao Xie, Xia-Xia Duan, Jia-Xuan Tan, Song Yang, Ling Meng, Qing-Hua Zhong, Wei-Di Lin, Jia-Ni Yang, Yao-Yao Xiao, Xueyu Jiang","doi":"10.1177/09645284241248465","DOIUrl":null,"url":null,"abstract":"Background:Cervical spondylosis (CS) is a prevalent disorder that can have a major negative impact on quality of life. Traditional conservative treatment has limited efficacy, and electroacupuncture (EA) is a novel treatment option. We investigated the application and molecular mechanism of EA treatment in a rat model of cervical intervertebral disk degeneration (CIDD).Methods:The CIDD rat model was established, following which rats in the electroacupuncture (EA) group received EA. For overexpression of IL-22 or inhibition of JAK2-STAT3 signaling, the rats were injected intraperitoneally with recombinant IL-22 protein (p-IL-22) or the JAK2-STAT3 (Janus kinase 2—signal transducer and activator of transcription protein 3) inhibitor AG490 after model establishment. Rat nucleus pulposus (NP) cells were isolated and cultured. Cell counting kit-8 and flow cytometry were used to analyze the viability and apoptosis of the NP cells. Expression of IL-22, JAK2 and STAT3 was determined using RT-qPCR. Expression of IL-22/JAK2-STAT3 pathway and apoptosis related proteins was detected by Western blotting (WB).Results:EA protected the NP tissues of CIDD rats by regulating the IL-22/JAK2-STAT3 pathway. Overexpression of IL-22 significantly promoted the expression of tumor necrosis factor (TNF)-α, IL-6, IL-1β, matrix metalloproteinase (MMP)3 and MMP13 compared with the EA group. WB demonstrated that the expression of IL-22, p-JAK2, p-STAT3, caspase-3 and Bax in NP cells of the EA group was significantly reduced and Bcl-2 elevated compared with the model group. EA regulated cytokines and MMP through activation of IL-22/JAK2-STAT3 signaling in CIDD rat NP cells.Conclusion:We demonstrated that EA affected apoptosis by regulating the IL-22/JAK2-STAT3 pathway in NP cells and reducing inflammatory factors in the CIDD rat model. The results extend our knowledge of the mechanisms of action underlying the effects of EA as a potential treatment approach for CS in clinical practice.","PeriodicalId":7257,"journal":{"name":"Acupuncture in Medicine","volume":"8 1","pages":""},"PeriodicalIF":2.4000,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Electroacupuncture improves apoptosis of nucleus pulposus cells via the IL-22/JAK2-STAT3 signaling pathway in a rat model of cervical intervertebral disk degeneration\",\"authors\":\"Sen Yan, Ling-Yao Xie, Xia-Xia Duan, Jia-Xuan Tan, Song Yang, Ling Meng, Qing-Hua Zhong, Wei-Di Lin, Jia-Ni Yang, Yao-Yao Xiao, Xueyu Jiang\",\"doi\":\"10.1177/09645284241248465\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Background:Cervical spondylosis (CS) is a prevalent disorder that can have a major negative impact on quality of life. Traditional conservative treatment has limited efficacy, and electroacupuncture (EA) is a novel treatment option. We investigated the application and molecular mechanism of EA treatment in a rat model of cervical intervertebral disk degeneration (CIDD).Methods:The CIDD rat model was established, following which rats in the electroacupuncture (EA) group received EA. For overexpression of IL-22 or inhibition of JAK2-STAT3 signaling, the rats were injected intraperitoneally with recombinant IL-22 protein (p-IL-22) or the JAK2-STAT3 (Janus kinase 2—signal transducer and activator of transcription protein 3) inhibitor AG490 after model establishment. Rat nucleus pulposus (NP) cells were isolated and cultured. Cell counting kit-8 and flow cytometry were used to analyze the viability and apoptosis of the NP cells. Expression of IL-22, JAK2 and STAT3 was determined using RT-qPCR. Expression of IL-22/JAK2-STAT3 pathway and apoptosis related proteins was detected by Western blotting (WB).Results:EA protected the NP tissues of CIDD rats by regulating the IL-22/JAK2-STAT3 pathway. Overexpression of IL-22 significantly promoted the expression of tumor necrosis factor (TNF)-α, IL-6, IL-1β, matrix metalloproteinase (MMP)3 and MMP13 compared with the EA group. WB demonstrated that the expression of IL-22, p-JAK2, p-STAT3, caspase-3 and Bax in NP cells of the EA group was significantly reduced and Bcl-2 elevated compared with the model group. EA regulated cytokines and MMP through activation of IL-22/JAK2-STAT3 signaling in CIDD rat NP cells.Conclusion:We demonstrated that EA affected apoptosis by regulating the IL-22/JAK2-STAT3 pathway in NP cells and reducing inflammatory factors in the CIDD rat model. The results extend our knowledge of the mechanisms of action underlying the effects of EA as a potential treatment approach for CS in clinical practice.\",\"PeriodicalId\":7257,\"journal\":{\"name\":\"Acupuncture in Medicine\",\"volume\":\"8 1\",\"pages\":\"\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2024-05-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acupuncture in Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/09645284241248465\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"INTEGRATIVE & COMPLEMENTARY MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acupuncture in Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/09645284241248465","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"INTEGRATIVE & COMPLEMENTARY MEDICINE","Score":null,"Total":0}
引用次数: 0
摘要
背景:颈椎病(CS)是一种普遍存在的疾病,会对生活质量造成严重的负面影响。传统的保守疗法疗效有限,而电针(EA)是一种新型的治疗方法。方法:建立颈椎间盘退行性病变(CIDD)大鼠模型,然后对电针组大鼠进行电针治疗。大鼠腹腔注射重组IL-22蛋白(p-IL-22)或JAK2-STAT3(Janus kinase 2-signal transducer and activator of transcription protein 3)抑制剂AG490,以过表达IL-22或抑制JAK2-STAT3信号转导。分离并培养大鼠髓核(NP)细胞。使用细胞计数试剂盒-8和流式细胞术分析NP细胞的活力和凋亡。使用 RT-qPCR 检测 IL-22、JAK2 和 STAT3 的表达。结果:EA 通过调节 IL-22/JAK2-STAT3 通路保护 CIDD 大鼠的 NP 组织。与 EA 组相比,IL-22 的过表达能显著促进肿瘤坏死因子(TNF)-α、IL-6、IL-1β、基质金属蛋白酶(MMP)3 和 MMP13 的表达。WB显示,与模型组相比,EA组NP细胞中IL-22、p-JAK2、p-STAT3、caspase-3和Bax的表达明显降低,而Bcl-2则升高。结论:我们证明了EA通过调节CIDD大鼠NP细胞的IL-22/JAK2-STAT3通路和减少炎症因子来影响细胞凋亡。这些结果扩展了我们对EA作用机制的认识,使其成为临床实践中治疗CS的一种潜在方法。
Electroacupuncture improves apoptosis of nucleus pulposus cells via the IL-22/JAK2-STAT3 signaling pathway in a rat model of cervical intervertebral disk degeneration
Background:Cervical spondylosis (CS) is a prevalent disorder that can have a major negative impact on quality of life. Traditional conservative treatment has limited efficacy, and electroacupuncture (EA) is a novel treatment option. We investigated the application and molecular mechanism of EA treatment in a rat model of cervical intervertebral disk degeneration (CIDD).Methods:The CIDD rat model was established, following which rats in the electroacupuncture (EA) group received EA. For overexpression of IL-22 or inhibition of JAK2-STAT3 signaling, the rats were injected intraperitoneally with recombinant IL-22 protein (p-IL-22) or the JAK2-STAT3 (Janus kinase 2—signal transducer and activator of transcription protein 3) inhibitor AG490 after model establishment. Rat nucleus pulposus (NP) cells were isolated and cultured. Cell counting kit-8 and flow cytometry were used to analyze the viability and apoptosis of the NP cells. Expression of IL-22, JAK2 and STAT3 was determined using RT-qPCR. Expression of IL-22/JAK2-STAT3 pathway and apoptosis related proteins was detected by Western blotting (WB).Results:EA protected the NP tissues of CIDD rats by regulating the IL-22/JAK2-STAT3 pathway. Overexpression of IL-22 significantly promoted the expression of tumor necrosis factor (TNF)-α, IL-6, IL-1β, matrix metalloproteinase (MMP)3 and MMP13 compared with the EA group. WB demonstrated that the expression of IL-22, p-JAK2, p-STAT3, caspase-3 and Bax in NP cells of the EA group was significantly reduced and Bcl-2 elevated compared with the model group. EA regulated cytokines and MMP through activation of IL-22/JAK2-STAT3 signaling in CIDD rat NP cells.Conclusion:We demonstrated that EA affected apoptosis by regulating the IL-22/JAK2-STAT3 pathway in NP cells and reducing inflammatory factors in the CIDD rat model. The results extend our knowledge of the mechanisms of action underlying the effects of EA as a potential treatment approach for CS in clinical practice.
期刊介绍:
Acupuncture in Medicine aims to promote the scientific understanding of acupuncture and related treatments by publishing scientific investigations of their effectiveness and modes of action as well as articles on their use in health services and clinical practice. Acupuncture in Medicine uses the Western understanding of neurophysiology and anatomy to interpret the effects of acupuncture.