中国中药杂志2026，Vol.51Issue(17)：4848-4859,12.DOI:10.19540/j.cnki.cjcmm.20260611.901
盘龙七片调控β2-肾上腺素能受体改善骨折早期损伤的机制研究
Research on mechanism of Panlongqi Tablets regulating β2-adrenergic receptors to improve early fracture injury
摘要
Abstract
This study aims to clarify the alleviating effects of Panlongqi Tablets(PLQP)on early fracture injuries and to reveal the mechanism of action through a multi-dimensional research method integrating network pharmacology,molecular docking,surface plasmon resonance(SPR),and animal experiments.Firstly,SD rats were randomized into sham operation,model,low-,medium-,and high-dose(0.16,0.32,and 0.64 g·kg-1,respectively)PLQP,and positive control(Jiegu Qili Capsules,0.10 g·kg-1)groups,with 12 rats in each group.Except the sham operation group,other groups were modeled for open transverse fracture of the tibia.After modeling,administration groups received corresponding drugs by gavage for 7 days.The efficacy was comprehensively evaluated in terms of local tenderness,mechanical pain,swelling degree,skin temperature,coagulation function,gait,and histopathological changes of fractures.Then,the fracture transcriptome dataset(GSE262132)from the GEO database and the corresponding targets of the blood-absorbed components of PLQP were collected.By comparison among different time points of fractures,the strongest time-effect intervention targets of PLQP were predicted,and they were then verified by molecular docking,SPR,and animal experiments.The results showed that PLQP significantly reduced the local swelling and skin temperature in the early stage of fractures,increased the mechanical pain threshold and local tenderness threshold of the affected limb,improved the gait and coagulation function of the affected limb,reduced inflammatory cell infiltration in the callus,lowered the content of fibrous connective tissue,increased the deposition of cartilage and collagen fibers,and promoted angiogenesis in model rats.Network pharmacological analysis indicated that β2-adrenergic receptor(ADRB2),interleukin(IL)-1β,endothelial nitric oxide synthase(NOS3),tumor necrosis factor(TNF),and endothelin-1(EDN1)were candidate strong targets for PLQP intervention in the early stage(7 days)of fractures.Among them,ADRB2 and EDN1 were specific.The results of molecular docking and SPR showed that the blood-absorbed components of PLQP,such as cryptotanshinone,11-keto-β-boswellic acid,tetrahydroberberine,β-ecdysterone,and tectorigenin,all had good binding activities with ADRB2.The results of immunohistochemistry,immunofluorescence,Western blot,and ELISA showed that PLQP upregulated the co-expression of macrophage CD68+ADRB2+,osteoblast Osterix+ADRB2+,and vascular endothelial cell CD31+ADRB2+in fracture callus,down-regulated the protein level of the M1 macrophage marker iNOS and inhibited the secretion of IL-1β,IL-6,and TNF-α,increased the level of the M2 macrophage marker CD206,and up-regulated the secretion of IL-10.In addition,PLQP increased the expression levels of VEGF and eNOS and the ratio of encoding gene EDN1(ET-1)to nitric oxide(NO).In conclusion,PLQP can significantly alleviate the redness,swelling,heat,and pain symptoms and functional disorders,correct the hypercoagulable state,improve microcirculation,inhibit inflammation,and promote angiogenesis,thereby accelerating fracture healing in rats.Its mechanism of action may be related to the up-regulation of ADRB2 expression for promoting M2-type polarization of macrophages,enhancing VEGF production,and regulating the ET-1/NO balance.The results are helpful in clarifying the therapeutic advantages,characteristics,and scientific connotations of Chinese patent medicines represented by PLQP and guiding the rational use of drugs in clinical practice.关键词
盘龙七片/胫骨骨折模型/ADRB2/巨噬细胞极化/抗炎/VEGF/局部微循环Key words
Panlongqi Tablets/tibial fracture model/ADRB2/macrophage polarization/anti-inflammatory/VEGF/local microcir-culation引用本文复制引用
王佳琳,孙丛丛,李文杰,刘春芳,林娜,李晓萱,郑楚沛,高双荣,严倩倩,赵清玉,沈佳韵,张彦琼,韩腾飞..盘龙七片调控β2-肾上腺素能受体改善骨折早期损伤的机制研究[J].中国中药杂志,2026,51(17):4848-4859,12.基金项目
中央级公益性科研院所基本科研业务费专项(ZXKT26009) （ZXKT26009）
中国中医科学院科技创新工程项目(CI2024E003,CI2024E003KC-05,CI2026A03805) （CI2024E003,CI2024E003KC-05,CI2026A03805）
国家重点研发计划"中医药现代化"专项(2022YFC3502000) （2022YFC3502000）
