中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (18): 3775-3783.doi: 10.12307/2025.642

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针刀干预后颈椎病大鼠头夹肌成纤维细胞生长因子家族及其受体的表达

刘福水1,钱嘉铭2,方  婷1,哈留娜2,3,赵小兰2,朱金超2,王小乐1   

  1. 1江西中医药大学附属医院,江西省南昌市  330006;2江西中医药大学,江西省南昌市  330004;3蒙古国传统医学技术研究院,乌兰巴托17032,蒙古国
  • 收稿日期:2024-06-13 接受日期:2024-07-30 出版日期:2025-06-28 发布日期:2024-11-27
  • 通讯作者: 王小乐,中医师,江西中医药大学附属医院,江西省南昌市 330006
  • 作者简介:刘福水,男,1979年生,江西省上饶市人,汉族,博士,主要从事针刀医学的基础与临床研究。
  • 基金资助:
    国家自然科学基金项目(82360940),项目负责人:刘福水;江西省自然科学基金重点项目(20224ACB206041),项目负责人:刘福水;江西省自然科学基金青年项目(20232BAB216117),项目负责人:王小乐;江西省教育厅科学技术研究项目(GJJ211206),项目负责人:刘福水;江西省教育厅科学技术研究项目(GJJ2200984),项目负责人:方婷;江西省教育厅科学技术研究项目(GJJ2200990),项目负责人:王小乐;江西省研究生创新专项资金项目(YC2023-B223),项目负责人:钱嘉铭

Effects of acupotomy on the expression of fibroblast growth factor family and its receptor in the splenius capitis muscles of rats with cervical spondylosis 

Liu Fushui1, Qian Jiaming2, Fang Ting1, Khaliunaa Tumurbaatar2, 3, Zhao Xiaolan2, Zhu Jinchao2, Wang Xiaole1   

  1. 1Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang 330006, Jiangxi Province, China; 2Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China; 3Institute of Traditional Medicine and Technology, Ulaanbaatar 17032, Mongolia
  • Received:2024-06-13 Accepted:2024-07-30 Online:2025-06-28 Published:2024-11-27
  • Contact: Wang Xiaole, Physician, Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang 330006, Jiangxi Province, China
  • About author:Liu Fushui, MD, Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang 330006, Jiangxi Province, China
  • Supported by:
    National Natural Science Foundation of China, No. 82360940 (to LFS); Key Project of Natural Science Foundation of Jiangxi Province, No. 20224ACB206041 (to LFS); Youth Project of Natural Science Foundation of Jiangxi Province, No. 20232BAB216117 (to WXL); Science and Technology Projects of Jiangxi Education Department, Nos. GJJ211206 (to LFS), GJJ2200984 (to FT), and GJJ2200990 (to WXL); Graduate Student Innovation Special Fund Project of Jiangxi Province, No. YC2023-B223 (to QJM)

摘要:


文题释义:
成纤维细胞生长因子家族(fibroblast growth factors,FGFs)及其受体激酶插入域蛋白受体(kinase insert domain protein receptor,KDR):成纤维细胞生长因子家族是一类广泛存在的多肽生长因子。激酶插入域蛋白受体是细胞膜上的一个信号传导受体,又名血管内皮细胞生长因子受体2,它们共同参与调节细胞增殖、凋亡等过程,维持机体稳定。

背景:针刀是治疗颈椎病的有效方法,临床疗效确切,但其关键分子机制尚不明晰。
目的:观察针刀干预对颈椎病大鼠头夹肌成纤维细胞生长因子家族及其受体激酶插入域蛋白受体表达的影响,分析针刀治疗颈椎病的作用机制。
方法:通过检索GEO数据库,获取符合该研究的芯片数据集GSE153761,采用生物信息学方法进行靶标初筛,然后进行动物实验。选取6月龄SPF级SD大鼠24只,随机均分为4组。模型组和针刀组大鼠采用动静力失衡性颈椎病造模方法制备颈椎病大鼠模型;假手术组不切断肌肉及韧带;针刀组造模成功后采用针刀干预,每周1次,共3次;并以正常大鼠作为对照。拍摄颈椎正侧位X射线片进行模型验证;旷场实验观察大鼠行为学变化;苏木精-伊红染色观察头夹肌病理结构;荧光定量PCR法和免疫组化法分别检测头夹肌成纤维细胞生长因子家族及其受体激酶插入域蛋白受体 mRNA及蛋白的表达情况。 
结果与结论:①生物信息学结果表明成纤维细胞生长因子家族/激酶插入域蛋白受体是激活磷脂酰肌醇3-激酶/蛋白激酶B上游的重要信号轴。②造模后大鼠椎间隙变窄,椎体前后缘、关节突骨质增生。③旷场实验中,造模后大鼠总距离、平均速度降低(P < 0.05),总休息时间延长(P < 0.05);治疗后针刀组大鼠总距离、平均速度大于模型组(P < 0.05),总休息时间短于模型组(P < 0.05)。④头夹肌病理提示颈肌受损,而针刀可改善颈肌劳损。⑤与正常组比较,模型组大鼠头夹肌成纤维细胞生长因子7、成纤维细胞生长因子9、成纤维细胞生长因子10、成纤维细胞生长因子18和激酶插入域蛋白受体 mRNA及蛋白表达均升高(P < 0.05);与模型组比较,针刀组以上指标均降低(P < 0.05)。⑥结果说明,针刀可能通过调节成纤维细胞生长因子7、成纤维细胞生长因子9、成纤维细胞生长因子10、成纤维细胞生长因子18及其受体激酶插入域蛋白受体的表达,修复劳损颈肌,从而改善椎间盘退变,这可能是针刀治疗颈椎病的关键靶点。                          

关键词: 针刀, 颈椎病, 成纤维细胞生长因子, 激酶插入域蛋白受体, 工程化细胞因子, 工程化组织构建

Abstract: BACKGROUND: Acupotomy is an effective method for the treatment of cervical spondylosis with definite clinical efficacy, but its key molecular mechanism is still unclear.
OBJECTIVE: To observe the effect of acupotomy intervention on the expression of fibroblast growth factor family and kinase insert domain protein receptor in the splenius capitis muscles of rats with cervical spondylosis, and to study the therapeutic mechanism of acupotomy in cervical spondylosis.
METHODS: The Genomics Expression Omnibus Database was searched to obtain the microarray dataset GSE153761, which was compatible with the study, and a bioinformatics approach was used for the initial screening of targets, followed by animal experiments. Twenty-four 6-month-old SPF grade Sprague-Dawley rats were randomly divided into four groups. The model of cervical spondylosis was established by unbalanced dynamic and static forces in the model and acupotomy groups. The muscles and ligaments were not cut in the sham operation group. After successful modeling, acupotomy intervention was performed in the acupotomy group, once a week, 3 times in total. Normal rats were selected as controls. The posteroanterior and lateral X-rays of the cervical spine were taken for modeling verification; the open-field tests were performed in all rats to observe behavioral changes; the pathological structure of the splenius capitis muscles was observed by hematoxylin-eosin staining; the mRNA and protein expression of fibroblast growth factor family and kinase insert domain protein receptor in the splenius capitis muscles was detected by fluorescent quantitative PCR and immunohistochemical method, respectively.
RESULTS AND CONCLUSION: Bioinformatics results indicated that fibroblast growth factor family/kinase insert domain protein receptor is an important signal axis for activating the phosphatidylinositol 3-kinase/protein kinase B signaling pathway. After modeling, the intervertebral space of the rats was narrowed, and the anterior and posterior borders of the vertebral body and the articular process were hyperosteogenous. In the open-field tests, the total distance and average speed in the model group were decreased after modeling (P < 0.05), while the total rest time in the model group was increased (P < 0.05). After treatment, the total distance and average speed in the acupotomy group were greater than those in the model group (P < 0.05), while the total rest time in the acupotomy group was shorter than that in the model group (P < 0.05). The pathological changes of the splenius capitis muscles indicated damage to the cervical muscle, and acupotomy improved cervical muscle strain. Compared with the normal group, The mRNA and protein expressions of fibroblast growth factor 7, fibroblast growth factor 9, fibroblast growth factor 10, fibroblast growth factor 18, and kinase insert domain protein receptor in the splenius capitis muscles were increased in the model group compared with the normal group (P < 0.05). In contrast, acupotomy treatment could downregulate the above indicators (P < 0.05). Thus, acupotomy may repair cervical muscle strain by regulating the expression of fibroblast growth factor 7, fibroblast growth factor 9, fibroblast growth factor 10, fibroblast growth factor 18, and kinase insert domain protein receptor, thereby improving intervertebral disc degeneration, which may be the key target for acupotomy treatment of cervical spondylosis.

中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程

Key words: acupotomy, cervical spondylosis, fibroblast growth factor, kinase insert domain protein receptor, engineered cytokine, engineered tissue construction

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