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王杰,邹德宝,李琰,王志洲,金鑫,候燕,王金凤,石威,姜红江.基于网络药理学结合实验验证探究骨碎补防治绝经后骨质疏松症的作用机制[J].湖南中医药大学学报,2022,42(9):1476-1484[点击复制] |
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| 基于网络药理学结合实验验证探究骨碎补防治绝经后骨质疏松症的作用机制 |
| 王杰,邹德宝,李琰,王志洲,金鑫,候燕,王金凤,石威,姜红江 |
| (安徽中医药大学第一临床医学院, 安徽 合肥 230000;山东省文登整骨医院, 山东 威海 264400) |
| 摘要: |
| 目的 通过网络药理学的途径探究骨碎补防治绝经后骨质疏松症（postmenopausal osteoporosis,PMOP）的有效物质成分与潜在的分子作用机制，并借助动物实验进行验证。方法 通过TCMSP数据库挖掘骨碎补的主要化学成分，根据ADME功能结合SwissTargetPrediction平台筛选出药物活性成分，并通过UniProt数据库进行靶点预测；通过GeneCards、OMIM、DrugBank、TTD数据库对PMOP主要作用靶点进行检索，借助STRING平台对药物、PMOP共同靶点创建PPI网络图；然后借助DAVID数据库进行GO和KEGG分析，并使用Cytoscape 3.8.0软件构建“靶点-通路”图。将40只雌鼠随机均分为空白组、假手术组、模型组及骨碎补组。由摘除大鼠双侧卵巢的方式构建PMOP模型，不间断灌胃12周，腹主动脉取血后处死，留取血清标本及双侧股骨进行雌二醇（estradiol,E2）、骨源性碱性磷酸酶（bone alkaline phosphatase,BALP）、抗酒石酸酸性磷酸酶（tartrate resistant acid phosphatase,TRAP）及骨密度（bone mineral density,BMD）检测。结果 筛选得到骨碎补治疗PMOP的主要活性成分为柚皮苷、木犀草素及山柰酚等，核心作用靶点包含MAPK1、MAPK3、TNF、TGF-β1等，通过Pathways in cancer、PI3K-Akt、TNF、HIF-1等信号通路参与调控PMOP。动物实验结果显示，空白组大鼠E2、BALP、TRAP血清含量与假手术组相比，差异无统计学意义(P＞0.05)；模型组大鼠E2、BALP血清含量明显低于假手术组(P＜0.01)，TRAP血清含量明显高于假手术组(P＜0.01)；骨碎补组大鼠E2、BALP血清含量较模型组明显增高(P＜0.05，P＜0.01)，TRAP血清含量比模型组明显下降(P＜0.05)。空白组大鼠股骨BMD与假手术组相比无统计学差异(P＞0.05)；模型组大鼠股骨BMD明显低于假手术组(P＜0.01)；骨碎补组大鼠股骨BMD高于模型组(P＜0.05)。结论 本研究证实了骨碎补防治PMOP具有多成分、多靶点、多通路的特点，能为PMOP的临床用药提供一定的理论参考和新药研发提供实验依据。 |
| 关键词: 网络药理学 骨碎补 绝经后骨质疏松症 信号通路 作用机制 实验验证 骨密度 |
| DOI：10.3969/j.issn.1674-070X.2022.09.010 |
| 投稿时间：2022-03-11 |
| 基金项目:山东省中医药科技发展计划项目(2019-0798)。 |
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| Mechanism of Gusuibu (Drynariae Rhizoma) in preventing and treating postmenopausal osteoporosis based on network pharmacology combined with experimental verification |
| WANG Jie,ZOU Debao,LI Yan,WANG Zhizhou,JIN Xin,HOU Yan,WANG Jinfeng,SHI Wei,JIANG Hongjiang |
| (The First Clinical School of Medicine, Anhui University of Chinese Medicine, Hefei, Anhui 230000, China;Shandong Wendeng Osteopathic Hospital, Weihai, Shandong 264400, China) |
| Abstract: |
| Objective To explore the active components and potential molecular mechanisms of Gusuibu (Drynariae Rhizoma) in preventing and treating postmenopausal osteoporosis (PMOP) by network pharmacology, and to verify by animal experiments. Methods The main chemical components of Gusuibu (Drynariae Rhizoma) were mined through the TCMSP database, and the active components of the drug were screened according to the ADME function combined with the SwissTargetPrediction platform, and the target was predicted through the UniProt database. The main targets of PMOP were searched through GeneCards, OMIM, DrugBank, and TTD databases. The STRING platform was used to create PPI network diagram for the common target of drug and PMOP. GO analysis and KEGG analysis were performed with the help of DAVID database, and the "target-pathway" network map was constructed with Cytoscape 3.8.0 software. A total of 40 female rats were randomly divided into blank group, sham operation group, model group and Gusuibu (Drynariae Rhizoma) group. The PMOP model was constructed by removing the bilateral ovaries of the rats. The rats were given continuous gavage for 12 weeks. The abdominal aorta was collected for blood, and the rats were sacrificed. Serum samples and bilateral femurs were collected for the detection of estradiol (E2), bone alkaline phosphatase (BALP), tartrate resistant acid phosphatase (TRAP) and bone mineral density (BMD). Results The main active components of Gusuibu (Drynariae Rhizoma) in the treatment of PMOP were naringin, luteolin and kaempferol. The main targets included MAPK1, MAPK3, TNF, TGF-β1, etc., and participated in the regulation of PMOP through Pathways in cancer, PI3K-Akt, TNF, HIF-1 and other signaling pathways. The results of animal experiments showed that there was no statistical difference in serum levels of E2, BALP and TRAP between the blank group and the sham operation group (P>0.05). The serum levels of E2 and BALP in the model group were significantly lower than those in the sham operation group (P<0.01), and the serum levels of TRAP in the model group were significantly higher than those in the sham operation group (P<0.01). The serum levels of E2 and BALP in the Gusuibu (Drynariae Rhizoma) group were significantly higher than those in the model group (P＜0.05, P＜0.01), and the serum levels of TRAP in the Gusuibu (Drynariae Rhizoma) group were significantly lower than those in the model group (P＜0.05). There was no statistical difference in the BMD of femur of the blank group compared with the sham operation group (P>0.05); the BMD of femur of the model group were significantly lower than those of the sham operation group (P<0.01); the BMD of femur of rats in the Gusuibu (Drynariae Rhizoma) group was higher than that in the model group (P<0.05). Conclusion This study confirms that Gusuibu (Drynariae Rhizoma) has the characteristics of being multi-component, multi-target and multi-pathway in the prevention and treatment of PMOP, which can provide a certain theoretical reference for the clinical drug use of PMOP and experimental basis for new drug research and development. |
| Key words: network pharmacology Gusuibu (Drynariae Rhizoma) postmenopausal osteoporosis signaling pathway mechanism of action experimental verification bone mineral density |
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