中国组织工程研究 ›› 2023, Vol. 27 ›› Issue (34): 5546-5553.doi: 10.12307/2023.560

• 生物材料综述 biomaterial review • 上一篇    下一篇

天然小分子化合物调控H型血管治疗骨骼相关疾病及在组织工程中的应用

徐正一,万乾炳,陈俊宇   

  1. 口腔疾病研究国家重点实验室,国家口腔疾病临床医学中心,四川大学华西口腔医院修复科,四川省成都市  610041
  • 收稿日期:2022-09-22 接受日期:2022-10-28 出版日期:2023-12-08 发布日期:2023-04-23
  • 通讯作者: 陈俊宇,副教授,硕士生导师,口腔疾病研究国家重点实验室,国家口腔疾病临床医学中心,四川大学华西口腔医院修复科,四川省成都市 610041
  • 作者简介:徐正一,男,1997年生,辽宁省沈阳市人,汉族,四川大学华西口腔医学院在读硕士,主要从事血管化组织工程学方向的研究。
  • 基金资助:
    国家自然科学基金项目 (81901060,82270961),项目负责人:陈俊宇;中国博士后科学基金特别资助项目 (2021T140483),
    项目负责人:陈俊宇

Natural small molecular compounds in the treatment of bone-related diseases by regulating type H blood vessels and its application in tissue engineering

Xu Zhengyi, Wan Qianbing, Chen Junyu   

  1. Department of Prosthodontics, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
  • Received:2022-09-22 Accepted:2022-10-28 Online:2023-12-08 Published:2023-04-23
  • Contact: Chen Junyu, Associate professor, Master’s supervisor, Department of Prosthodontics, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
  • About author:Xu Zhengyi, Master candidate, Department of Prosthodontics, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
  • Supported by:
    National Natural Science Foundation of China, Nos. 81901060, 82270961 (to CJY); Special Funded Project of China Postdoctoral Science Foundation, No. 2021T140483 (to CJY)

摘要:


文题释义:

H型血管:H型血管是一种能高表达血小板内皮细胞黏附分子1(PECAM-1/CD31)和唾液糖蛋白内黏蛋白(Endomucin,Emcn)的特殊血管亚型,具有独特的时空及形态特征,在血管生成与骨生成两种生理过程的偶联中起重要作用。
天然小分子化合物:是一种从天然产物及其活性代谢物中发现的具有生理调节功能的小分子化合物或经过化学家的结构改造最终得到具有治疗作用的药物活性先导物。

背景:H型血管是近年来新发现的一种能够偶联成血管和成骨两种生理过程的特殊血管亚型,在骨骼系统的生理及病理过程中均扮演重要角色。天然小分子化合物具有来源广泛、毒副反应低等优点。近年来研究发现天然小分子化合物对H型血管也具有调控作用。
目的:总结H型血管的基本特征,并讨论几种天然小分子化合物在治疗骨相关疾病治疗中的应用现状及前景。
方法:在Web of Science、PubMed、中国知网和万方数据库中,以“H型血管、天然小分子化合物、天然小分子药物、中药活性成分”为中文检索词,以“type H vessel,H-type vessel,type H microvessel,type H blood vessel,CD31hiEmcnhi endothelial cell,CD31hiEndomucinhi blood vessel,CD31(hi)Emcn(hi) endothelial cell,specific vessel subtype,natural small molecular compounds,Chinese medicine,Chinese traditional medicine,Chinese plant extracts”为英文检索词进行文献检索。检索时间范围为2014年1月至2022年6月。通过阅读文题和摘要进行初步筛选,排除中英文文献重复性研究及内容不相关的文献,经文献质量评价后,最后纳入65篇文献进行综述。 

结果与结论:①H型血管是一种特殊血管亚型,主要分布于长骨干骺端及骨内膜处,在扁骨与不规则骨中也有分布,且在多数部位,有典型的柱状或栅栏状排列结构;H型血管的长度及数量在不同部位均呈现年龄相关性。②H型血管在偶联成骨-成血管两种生理过程中起到重要作用,其可以通过血管旁分泌的作用对成骨系和破骨系细胞发挥募集与调节作用。③H型血管在骨疾病的发生发展中扮演重要角色,多种天然小分子化合物在通过调控H型血管治疗骨关节炎、骨质疏松、骨折和去负荷性骨丢失等疾病中具有较好效果;例如三七的提取物邻苯二甲酸二叔丁酯可以抑制异常的H型血管生成,以缓解骨关节炎病情进展,人参的提取物人参皂甙化合物K可以促进愈伤组织中H型血管生成,加快骨折愈合。④鉴于组织工程支架负载药物及细胞因子调控H型血管治疗骨疾病以及天然小分子化合物在调控H型血管所体现出的较好效果,将组织工程支架与天然小分子化合物结合调控H型血管显示出良好的前景。

https://orcid.org/0000-0001-5852-9167(徐正一);https://orcid.org/0000-0003-1717-5782(陈俊宇)

中国组织工程研究杂志出版内容重点:生物材料;骨生物材料口腔生物材料纳米材料缓释材料材料相容性组织工程

关键词: H型血管, 天然小分子化合物, 骨组织工程, 血管生成, 骨代谢, 骨关节炎, 骨折, 骨质疏松

Abstract: BACKGROUND: Type H blood vessels, a specific subtype of vessels newly discovered in recent years, have been identified to couple angiogenesis and osteogenesis. They play an important role in the physiological and pathological processes of the skeletal system. Natural small molecular compounds have the advantages of widespread sources, low toxic and side effects. In recent years, studies have found that natural small molecular compounds can regulate type H blood vessels. 
OBJECTIVE: To review the basic characteristics of type H blood vessels and discuss the application status and prospect of several natural small molecular compounds in the treatment of bone-related diseases. 
METHODS: The literature search was performed in Web of Science, PubMed, CNKI and WanFang databases. Relevant articles published from January 2014 to June 2022 were researched with the key words of “type H vessel, natural small molecular compounds, natural small molecule drugs, active ingredients of traditional Chinese medicine” in Chinese and “type H vessel, H-type vessel, type H microvessel, type H blood vessel, CD31hiEmcnhi endothelial cell, CD31hiEndomucinhi blood vessel, CD31(hi)Emcn(hi) endothelial cell, specific vessel subtype, natural small molecular compounds, Chinese medicine, Chinese traditional medicine, Chinese plant extracts” in English. After reading the titles and abstracts, repetitive studies, low-quality or irrelevant articles were excluded. Finally, 65 articles were included for review.
RESULTS AND CONCLUSION: (1) Type H vessel is a special subtype of blood vessels mainly found in the metaphysis and endosteum of long bones, and also exist in other types of bones. At most sites, type H vessels are arranged linearly with a distinctive columnar or palisade-like structure. Moreover, type H blood vessels have significant age-related changes in length and abundance of vascular buds. (2) Type H vessels play an important role in couple angiogenic and osteogenic processes via blood flow as well as the recruitment and regulation of osteoblasts lineage and osteoclast lineage. (3) Type H vessels are important in the occurrence and development of bone disease. Natural small molecular compounds show a good prospect in the study of treating bone-related diseases including osteoarthritis, osteoporosis, bone fracture, and unloading-induced bone loss via regulating type H blood vessels. For example, diterbutyl phthalate, the extract of Panax notoginseng, blunted the aberrant formation of type H vessels to prevent osteoarthritis progression. Ginsenoside compound K, the extract of Panax ginseng, can promote the formation of type H vessels in callus and accelerate fracture healing. (4) In view of the prospective effect of tissue engineering scaffolds loading drugs and cytokines on type H blood vessels in the treatment of bone diseases and natural small molecular compounds in regulating type H blood vessels, the combination of tissue engineering scaffolds and natural small molecular compounds to regulate type H blood vessels is a potential strategy.

Key words: type H vessel, natural small molecular compound, bone tissue engineering, angiogenesis, bone metabolism, osteoarthritis, bone fracture, osteoporosis

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