[1]张楚,王骁汉,马兆臣,等.补肾壮骨方治疗非创伤性股骨头坏死肝肾亏虚证的功效内涵解析及临床验证[J].中医正骨,2024,36(07):10-16.
　ZHANG Chu,WANG Xiaohan,MA Zhaochen,et al.Connotation analysis and clinical verification of efficacy of Bushen Zhuanggu Fang(补肾壮骨方)against non-traumatic osteonecrosis of the femoral head with syndrome of liver-kidney deficiency[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2024,36(07):10-16.
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补肾壮骨方治疗非创伤性股骨头坏死肝肾亏虚证的功效内涵解析及临床验证()
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《中医正骨》[ISSN:1001-6015/CN:41-1162/R]

卷:
第36卷
期数:
2024年07期
页码:
10-16
栏目:
临床研究
出版日期:
2024-07-20

文章信息/Info

Title:
Connotation analysis and clinical verification of efficacy of Bushen Zhuanggu Fang(补肾壮骨方)against non-traumatic osteonecrosis of the femoral head with syndrome of liver-kidney deficiency
作者:
张楚1; 王骁汉2; 马兆臣3; 刘毓东3; 李涛3; 林娜3; 陈卫衡2; 张彦琼1
1.福建中医药大学药学院,福建 福州 350122; 2.北京中医药大学第三附属医院,北京 100029; 3.中国中医科学院中药研究所,北京 100700
Author(s):
ZHANG Chu1; WANG Xiaohan2; MA Zhaochen3; LIU Yudong3; LI Tao3; LIN Na3; CHEN Weiheng2; ZHANG Yanqiong1
1.College of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,Fujian,China 2.Beijing University of Chinese Medicine Third Affiliated Hospital,Beijing 100029,China 3.Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China
关键词:
股骨头坏死;  肝肾亏虚;  补肾壮骨方;  网络药理学;  临床试验
Keywords:
femur head necrosis;  deficiency of liver and kidney;  Bushen Zhuanggu Fang;  network pharmacology;  clinical trial
摘要:
目的:探讨补肾壮骨方治疗非创伤性股骨头坏死(non-traumatic osteonecrosis of the femoral head,NONFH)肝肾亏虚证的功效内涵。方法:①网络药理学研究。检索TCMIP v2.0、ETCM2.0、HERB数据库,收集补肾壮骨方的靶标基因,从项目组前期研究中获取NONFH肝肾亏虚证相关差异表达基因,以NONFH肝肾亏虚证典型症状为关键词检索NONFH肝肾亏虚证典型症状相关基因。将上述基因合并,构建补肾壮骨方治疗NONFH肝肾亏虚证蛋白质互作网络,从中筛选关键靶标基因,并对其进行KEGG信号通路富集分析,结合文献对相关信号通路进行药理作用分析。以靶标基因与信号通路、信号通路与药理作用的映射关系为基础,结合文献报道,构建补肾壮骨方治疗NONFH肝肾亏虚证“组方中药-关键靶标-信号通路-功效-药理作用-临床症状”关联网络。②临床研究。选择77例(120髋)NONFH肝肾亏虚证患者,采用口服补肾壮骨方治疗6个月。分别采用股骨头坏死临床疗效评价标准和北京中医药大学X线评价系统进行临床疗效和影像学疗效评价。结果:①网络药理学研究结果。从构建的补肾壮骨方治疗NONFH肝肾亏虚证蛋白质互作网络中共筛选出556个关键靶标基因,这些基因共参与39条与NONFH肝肾亏虚证有关的信号通路,主要涉及纠正骨代谢紊乱、纠正脂代谢紊乱、矫正免疫-炎症失衡、改善血液循环受阻4种药理作用。纠正骨代谢紊乱涉及靶标基因183个,纠正脂代谢紊乱涉及靶标基因176个,矫正免疫-炎症失衡涉及靶标基因171个,改善血液循环受阻涉及靶标基因125个。构建的“组方中药-关键靶标-信号通路-功效-药理作用-临床症状”关联网络直观显示了补肾壮骨方治疗NONFH肝肾亏虚证的功效内涵。②临床研究结果。临床疗效评价结果显示,治疗6个月后患者的髋关节疼痛强度评分、髋关节屈曲功能评分、行走距离评分及临床疗效总分均较治疗前降低[(5.86±1.96)分,(2.26±1.84)分,t=25.672,P=0.000;(5.76±1.62)分,(3.46±1.68)分,t=38.411,P=0.000;(6.31±1.41)分,(0.78±0.74)分,t=46.771,P=0.000;(5.92±1.18)分,(2.32±1.06)分,t=48.263,P=0.000]; 临床疗效优88髋、良28髋、可2髋、差2髋。影像学疗效评价结果显示,治疗后3年影像学疗效优17髋、良25髋、可67髋、差11髋; 股骨头形态稳定109髋、进展11髋,坏死灶改善67髋、稳定34髋、进展19髋,骨关节炎稳定100髋、进展20髋。结论:补肾壮骨方治疗NONFH肝肾亏虚证的机制为纠正骨代谢和脂代谢紊乱、免疫-炎症失衡及血液循环受阻,其中纠正骨代谢紊乱可能是最主要的机制。
Abstract:
Objective:To investigate the efficacy connotation of Bushen Zhuanggu Fang(补肾壮骨方,BSZGF)in treating non-trauma-tic osteonecrosis of the femoral head(NONFH)with syndrome of liver-kidney deficiency(LKD).Methods:①The network pharmacology-based research.The candidate target genes of BSZGF were screened and collected by retrieving the TCMIP v2.0,ETCM2.0 and HERB databases.The differentially expressed genes(DEGs)related to LKD syndrome of NONFH were extracted from the previous research performed by the project team,and the typical symptom-related genes of LKD syndrome of NONFH were searched in the HPO database by taking the typical symptoms of LKD syndrome of NONFH as keywords.The aforementioned genes were merged as the target gene sets to build the protein-protein interaction(PPI)network of BSZGF against the LKD syndrome of NONFH,from which the key target genes were screened and then subjected to KEGG signaling pathway enrichment analysis,furthermore,the pharmacological actions of the related signaling pathways were analyzed based on the relevant articles.After that,an association network of Chinese herb-key target-signaling pathway-efficacy-pharmacological action-clinical symptom for BSZGF against the LKD syndrome of NONFH was constructed based on the mapping relationships between target genes and signaling pathways as well as between signaling pathways and pharmacological actions,and the reports in the relevant articles.②Clinical research.Seventy-seven NONFH patients(120 hips)with LKD syndrome were selected and treated with oral application of BSZGF for 6 months.After that,the clinical outcomes and radiological outcomes were assessed by using the evaluation criteria for clinical efficacy of femoral head necrosis and the X-ray evaluation system of Beijing University of Chinese Medicine,respectively.Results:①The results of network pharmacology-based research.Five hundred and fifty-six key target genes were screened out from the constructed PPI network of BSZGF against the LKD syndrome of NONFH.The results of KEGG signaling pathway enrichment analysis and the reports of relevant articles suggested that the 556 key target genes participated in 39 LKD syndrome of NONFH-related signaling pathways,mainly involved in rectifying the bone metabolism disorder(183 target genes),rectifying the lipid metabolism disorder(176 target genes),rectifying the immune-inflammatory imbalance(171 target genes),and improving the blood circulation obstruction(125 target genes).The established association network diagram of Chinese herb-key target-signaling pathway-efficacy-pharmacological action-clinical symptom intuitively illustrated the efficacy connotation of BSZGF in treating the LKD syndrome of NONFH.②The results of clinical research.The results of evalu-ation on clinical outcomes showed that the scores for hip pain intensity,hip flexion function,walking distance,and total clinical efficacy all decreased after 6-month treatment compared to pre-treatment(5.86±1.96 vs 2.26±1.84 points,t=25.672,P=0.000; 5.76±1.62 vs 3.46±1.68 points,t=38.411,P=0.000; 6.31±1.41 vs 0.78±0.74 points,t=46.771,P=0.000; 5.92±1.18 vs 2.32±1.06 points,t=48.263,P=0.000).The clinical outcome was excellent in 88 hips,good in 28 hips,fair in 2 hips,and poor in 2 hips.The results of evaluation on radiological outcomes showed that,at 3 years after the treatment,the radiological outcome was excellent in 17 hips,good in 25 hips,fair in 67 hips,and poor in 11 hips; the morphology of the femoral head was stable in 109 hips,and progressed in 11 hips; the necrotic foci was improved in 67 hips,stabilized in 34 hips,and progressed in 19 hips; and the osteoarthritis was stable in 100 hips,and progressed in 20 hips.Conclusion:The BSZGF exerts the effects by rectifying the disorders of bone metabolism and lipid metabolism,rectifying the imbalance of immune-inflammation,and improving the obstruction of blood circulation in treatment of NONFH with LKD syndrome,among which rectifying the disorder of bone metabolism may be the most primary mechanism.

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备注/Memo

备注/Memo:
基金项目:国家自然科学基金项目(82030122)
通讯作者:张彦琼 E-mail:yqzhang@icmm.ac.cn
更新日期/Last Update: 1900-01-01