84年鼠女哪年财运最旺,857comvvv色九欧美激情|85PO_87国产精品欲av国产av资源

[1]王偉偉,歐志學,章曉云,等.補腎壯筋湯治療膝骨關節(jié)炎作用機制的網(wǎng)絡藥理學研究[J].中醫(yī)正骨,2022,34(07):6-14,26.
　WANG Weiwei,OU Zhixue,ZHANG Xiaoyun,et al.Mechanism of Bushen Zhuangjin Tang(補腎壯筋湯)in treatment of knee osteoarthritis:a network pharmacology-based study[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2022,34(07):6-14,26.
點擊復制

補腎壯筋湯治療膝骨關節(jié)炎作用機制的網(wǎng)絡藥理學研究()
分享到：

《中醫(yī)正骨》[ISSN:1001-6015/CN:41-1162/R]

卷:
第34卷
期數(shù):
2022年07期
頁碼:
6-14,26
欄目:
基礎研究
出版日期:
2022-07-20

文章信息/Info

Title:
Mechanism of Bushen Zhuangjin Tang(補腎壯筋湯)in treatment of knee osteoarthritis:a network pharmacology-based study
作者:
王偉偉1; 歐志學2; 章曉云1; 李統(tǒng)1
(1.廣西中醫(yī)藥大學附屬瑞康醫(yī)院,廣西 南寧 530011; 2.桂林市中醫(yī)醫(yī)院,廣西 桂林 541002)
Author(s):
WANG Weiwei1; OU Zhixue2; ZHANG Xiaoyun1; LI Tong1
1.Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine,Nanning 530011,Guangxi,China 2.Guilin Municipal Hospital of Traditional Chinese Medicine,Guilin 541002,Guangxi,China
關鍵詞:
骨關節(jié)炎; 膝;  補腎壯筋湯;  網(wǎng)絡藥理學;  藥物作用機制
Keywords:
osteoarthritis; knee;  Bushen Zhuangjin Tang;  network pharmacology;  mechanism of drug action
摘要:
目的:采用網(wǎng)絡藥理學方法探討補腎壯筋湯治療膝骨關節(jié)炎(knee osteoarthritis,KOA)的作用機制。方法:使用中藥系統(tǒng)藥理學數(shù)據(jù)庫與分析平臺、中藥分子機制的生物信息學分析工具,檢索和篩選補腎壯筋湯的活性成分,然后借助PubChem和Swiss TargetPrediction數(shù)據(jù)庫檢索和篩選活性成分對應的靶點,預測補腎壯筋湯的作用靶點。在GeneCard數(shù)據(jù)庫中檢索KOA的靶點。將檢索到的KOA靶點和補腎壯筋湯靶點取交集,獲取補腎壯筋湯治療KOA的作用靶點。通過String數(shù)據(jù)庫和Cytoscape3.7.2軟件分析補腎壯筋湯治療KOA的作用靶點,構建補腎壯筋湯治療KOA靶點蛋白互作網(wǎng)絡,篩選補腎壯筋湯治療KOA的關鍵靶點。篩選與補腎壯筋湯治療KOA的作用靶點有關的活性成分,并將其與補腎壯筋湯治療KOA的作用靶點、補腎壯筋湯組成中藥一同輸入Cytoscape3.7.2軟件,構建補腎壯筋湯治療KOA“中藥-活性成分-靶點”網(wǎng)絡,分析補腎壯筋湯治療KOA的主要活性成分。利用DAVID數(shù)據(jù)庫和R3.6.2軟件進行補腎壯筋湯治療KOA靶點基因GO富集分析和KEGG富集分析。運用Autodock vina軟件將補腎壯筋湯治療KOA的主要活性成分與關鍵靶點進行分子對接,對其結合能進行評估,并通過Pymol軟件將結果可視化。結果:共篩選到補腎壯筋湯的活性成分99個、預測到對應的靶點768個,通過與檢索到的989個KOA靶點取交集,共獲得補腎壯筋湯治療KOA的靶點172個。通過分析共獲得15個補腎壯筋湯治療KOA的關鍵靶點[促分裂原活化的蛋白激酶(mitogen activated protein kinase,MAPK)1、Akt激酶(akt kinase,AKT)1、淀粉樣前體蛋白、Harvey大鼠肉瘤病毒致癌基因同源物、MAPK8、白細胞介素(interleukin,IL)-6、激肽原1、血管內(nèi)皮生長因子A、熱激蛋白90AA1、JUN原癌基因、腫瘤壞死因子(tumor necrosis factor,TNF)、MAPK14、IL-2、表皮生長因子受體、凝血因子Ⅱ],5個補腎壯筋湯治療KOA的主要活性成分(漢黃芩素、啤酒甾醇、槲皮素、黃芩素、山奈酚)。GO富集分析結果顯示,補腎壯筋湯治療KOA主要涉及RNA聚合酶Ⅱ啟動子轉錄的調(diào)控、凋亡過程的負調(diào)控、信號傳導、調(diào)控細胞增殖、轉錄等生物過程,蛋白質(zhì)結合、ATP結合、鋅離子結合、相同蛋白質(zhì)結合、酶結合等分子功能,以及細胞內(nèi)質(zhì)膜、細胞質(zhì)、細胞核、胞質(zhì)溶膠、核質(zhì)等細胞組分; KEGG富集分析共篩選出磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)-AKT、MAPK、TNF等3條主要信號通路。分子對接結果顯示,5個主要活性成分與15個關鍵靶點均有良好的結合能力,結合能均≤-5.0 kJ·mol-1; 分子對接圖顯示,活性成分大多嵌入靶點活性口袋的疏水區(qū),結合模式多以π-π作用和氫鍵為主,提示其具有較好的結合活性,結合后構象穩(wěn)定。結論:補腎壯筋湯治療KOA的作用機制可能是通過漢黃芩素、啤酒甾醇、槲皮素、黃芩素、山奈酚等活性成分,參與調(diào)控RNA聚合酶Ⅱ啟動子轉錄、凋亡過程、信號傳導、細胞增殖、轉錄,影響PI3K-AKT、MAPK、TNF等信號通路。
Abstract:
Objective:To explore the mechanism of Bushen Zhuangjin Tang(補腎壯筋湯,BSZJT)in treatment of knee osteoarthritis(KOA)by using network pharmacological approach.Methods:The active ingredients of BSZJT were screened via retrieving traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP)using the bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine(BATMAN-TCM),and their corresponding targets were screened out from PubChem database and Swiss TargetPrediction database for predicting the action targets of BSZJT.The action targets of BSZJT against KOA were obtained through overlapping the targets of BSZJT with KOA that retrieved from the GeneCard database,and they were analyzed by using String database,furthermore,the target protein-protein interaction(PPI)network of BSZJT against KOA was built by using Cytoscape3.7.2 software for screening the key targets of BSZJT against KOA.The active ingredients related to the action targets of BSZJT against KOA were screened out and were input into the Cytoscape3.7.2 software together with the action targets of BSZJT against KOA and the Chinese materia medica(CMM)in BSZJT,and the herb-active ingredient-target network of BSZJT against KOA was constructed for analysing the main active ingredients of BSZJT against KOA.The Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed on the target genes of BSZJT against KOA by using DAVID database and R3.6.2 software to dig biological functions and pathways of the target genes.Moreover,the molecular docking was conducted between the main active ingredients of BSZJT against KOA and its key targets by using Autodock vina software,and their binding energy was evaluated with the results visualized by Pymol software.Results:Ninety-nine active ingredients of BSZJT were screened out,and 768 corresponding targets were predicted,meanwhile,172 targets of BSZJT against KOA were obtained through overlapping the 989 KOA targets with the 768 predicted BSZJT targets.As revealed by the analysis,15 key targets(mitogen activated protein kinase(MAPK)1,akt kinase(AKT)1,amyloid precursor protein(APP),harvey rat sarcoma virus oncogene homolog(HRAS),MAPK8,interleukin(IL)-6,kininogen 1(KNG1),vascular endothelial growth factor A(VEGFA),heat shock protein 90AA1(HSP90AA1),JUN proto-oncogene(JUN),tumor necrosis factor(TNF),MAPK14,IL-2,epidermal growth factor receptor(EGFR)and blood coagulation factorⅡ(F2))and 5 main active ingredients(wogonin,cerevisterol,quercetin,baicalein and kaempferol)of BSZJT against KOA were obtained.The results of GO function enrichment analysis indicated that the target genes of BSZJT against KOA mainly participated in such biological processes(BPs)as regulation of transcription from RNA polymeraseⅡpromoter,negative regulation of apoptotic process,signal transduction,regulation of cell proliferation and transcription,the molecular functions(MFs)as protein binding,ATP binding,zinc ion binding,identical protein binding,enzyme binding,and the cellular components(CCs)as intracellular plasma membrane,cytoplasm,nucleus,cytosol,nucleoplasm.The results of KEGG pathway enrichment analysis showed that the target genes of BSZJT against KOA mainly acted on 3 major signaling pathways,such as signaling pathways of phosphatidylinositol 3-kinase(PI3K)-AKT,MAPK and TNF.The results of molecular docking showed that the 5 main active ingredients had good binding ability to the 15 key targets with the binding energy≤-5.0 kJ/mol.The molecular docking diagram illustrated that the active ingredients were mostly embedded in the hydrophobic region of the active pocket in targets with the binding modes mainly as π-π interaction and hydrogen bonds,which suggested they had good binding activity and the conformation was stabilized after binding.Conclusion:The mechanism of BSZJT against KOA may be that it participate in the BPs including regulation of transcription from RNA polymeraseⅡpromoter,apoptotic process,signal transduction,cell proliferation and transcription to affect the signaling pathways of PI3K-AKT,MAPK and TNF through the active ingredients of wogonin,cerevisterol,quercetin,baicalein and kaempferol.

參考文獻/References:

[1] 中國中醫(yī)藥研究促進會骨傷科分會.膝骨關節(jié)炎中醫(yī)診療指南(2020年版)[J].中醫(yī)正骨,2020,32(10):1-14.
[2] LIPINSKI C A.Rule of five in 2015 and beyond:target and ligand structural limitations,ligand chemistry structure and drug discovery project decisions[J].Adv Drug Deliv Rev,2016,101:34-41.
[3] ABUSARAH J,BENABDOUNE H,SHI Q,et al.Elucidating the role of protandim and 6-gingerol in protection against osteoarthritis[J].J Cell Biochem,2017,118(5):1003-1013.
[4] CHOWDHURY N S,SOHRAB M H,RANA M S,et al.Cytotoxic naphthoquinone and azaanthraquinone derivatives from an endophytic fusarium solani[J].J Nat Prod,2017,80(4):1173-1177.
[5] LEYVA-LPEZ N,GUTIERREZ-GRIJALVA E P,AMBRIZ-PEREZ D L,et al.Flavonoids as cytokine modulators:a possible therapy for inflammation-related diseases[J].Int J Mol Sci,2016,17(6):921.
[6] GUIMARÃES G C,PIVA H,ARAUJO G C,et al.Binding investigation between M2-1protein from hRSV and acetylated quercetin derivatives:1H NMR,fluorescence spectroscopy,and molecular docking[J].Int J Biol Macromol,2018,111:33-38.
[7] KIM J R,YOO J J,KIM H A.Therapeutics in osteoarthritis based on an understanding of its molecular pathogenesis[J].Int J Mol Sci,2018,19(3):674.
[8] ZHANG X H,XU X X,XU T.Ginsenoside ro suppresses interleukin-1β-induced apoptosis and inflammation in rat chondrocytes by inhibiting NF-κB[J].Chin J Nat Med,2015,13(4):283-289.
[9] 羅曉平,于之倫,鄧超,等.黃芩素對2,4,6-三硝基苯磺酸誘導的小鼠實驗性腸炎的作用和機制[J].中國藥理學與毒理學雜志,2017,31(6):541-546.
[10] 楊波,龍慧,王鄭鋼,等.黃芩素通過促進miR-29a-3p抑制MAP2K6改善骨性關節(jié)炎模型大鼠軟骨細胞退化[J].中藥藥理與臨床,2019,35(6):32-37.
[11] IMRAN M,RAUF A,SHAH Z A,et al.Chemo-preventive and therapeutic effect of the dietary flavonoid kaempferol:a comprehensive review[J].Phytother Res,2019,33(2):263-275.
[12] KADIOGLU O,NASS J,SAEED M E,et al.Kaempferol is an anti-inflammatory compound with activity towards NF-κB pathway proteins[J].Anticancer Res,2015,35(5):2645-2650.
[13] LI Q,WU M,FANG G,et al.MicroRNA-186-5p downregulation inhibits osteoarthritis development by targeting MAPK1[J].Mol Med Rep,2021,23(4):253.
[14] YANG Y,GU Y,ZHAO H,et al.Loganin attenuates osteoarthritis in rats by inhibiting IL-1β-induced catabolism and apoptosis in chondrocytes via regulation of phosphatidylinositol 3-kinases(PI3K)/Akt[J].Med Sci Monit,2019,25:4159-4168.
[15] WU X Y,LIU W T,WU Z F,et al.Identification of HRAS as cancer-promoting gene in gastric carcinoma cell aggressiveness[J].Am J Cancer Res,2016,6(9):1935-1948.
[16] CHEN Y T,HUANG Z Y,TANG H H,et al.Pterostilbene sensitizes cisplatin-resistant human bladder cancer cells with oncogenic HRAS[J].Cancers(Basel),2020,12(10):2869.
[17] LÜ G,LI L,WANG B,et al.LINC00623/miR-101/HRAS axis modulates IL-1β-mediated ECM degradation,apoptosis and senescence of osteoarthritis chondrocytes[J].Aging(Albany NY),2020,12(4):3218-3237.
[18] JIANG H,DAI J,ZHANG C,et al.Circ_0045714 alleviates TNF-α-induced chondrocyte injury and extracellular matrix degradation through miR-218-5p/HRAS axis[J].J Bioenerg Biomembr,2021,53(1):97-107.
[19] YUDUSHKIN I.Control of Akt activity and substrate phosphorylation in cells[J].IUBMB Life,2020,72(6):1115-1125.
[20] 顏春魯,李盛華,安方玉,等.右歸丸通過PI3K/Akt/mTOR信號通路對膝骨關節(jié)炎模型鼠軟骨組織保護作用的研究[J].中國骨質(zhì)疏松雜志,2020,26(3):318-322.
[21] CHU X, YU T, HUANG X,et al.Tomatidine suppresses inflammation in primary articular chondrocytes and attenuates cartilage degradation in osteoarthritic rats[J].Aging(Albany NY),2020,12(13):12799-12811.
[22] 謝文鵬,楊靈森,馬亮,等.基于p38 MAPK信號通路探討蒼膝通痹膠囊對KOA大鼠關節(jié)軟骨的保護作用[J].中國實驗方劑學雜志,2020,26(18):70-76.

相似文獻/References:

[1]樊慶陽,任凱晶.定制3D打印切模輔助全膝關節(jié)置換術治療 膝骨關節(jié)炎合并股骨干骨折畸形愈合[J].中醫(yī)正骨,2015,27(11):37.
[2]劉曉雅,孫永強,劉國杰.主動快速康復鍛煉對全膝關節(jié)置換術后關節(jié)活動度的影響[J].中醫(yī)正骨,2015,27(09):73.
[3]鄭春松,葉蕻芝,李西海,等.透骨消痛膠囊中補腎柔肝藥和活血祛風藥治療 骨關節(jié)炎作用方式的計算機模擬比較[J].中醫(yī)正骨,2015,27(07):6.
　ZHENG Chunsong,YE Hongzhi,LI Xihai,et al.Comparison of the mode of action of Bushen Rougan(補腎柔肝)drugs versus Huoxue Qufeng(活血祛風)drugs contained in Tougu Xiaotong Jiaonang(透骨消痛膠囊)for the treatment of osteoarthritis:A computer simulation study[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2015,27(07):6.
[4]宋兵華,孫俊英,倪增良,等.全膝關節(jié)置換術前CT測量股骨后髁角的臨床意義[J].中醫(yī)正骨,2015,27(07):38.
[5]鄭春松,葉蕻芝,李西海,等.獨活寄生湯含藥血清對白細胞介素1β誘導的 退變關節(jié)軟骨細胞中基質(zhì)金屬蛋白酶 和環(huán)氧化酶2表達的影響[J].中醫(yī)正骨,2015,27(12):1.
　ZHENG Chunsong,YE Hongzhi,LI Xihai,et al.Impact of Duhuo Jisheng Tang(獨活寄生湯)medicated serum on expression of matrix metalloproteinase and cyclooxygenase 2 in degenerative articular chondrocytes induced by interleukin-1 beta[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2015,27(07):1.
[6]王金良,孫京濤,李玲,等.骨水泥聯(lián)合螺釘修復全膝關節(jié)置換術中 脛骨平臺內(nèi)側骨缺損[J].中醫(yī)正骨,2015,27(12):55.
[7]馮榮,王平,李炳奇,等.鈹針刺絡拔罐結合中藥口服治療膝骨關節(jié)炎合并 原發(fā)性血小板增多癥1例[J].中醫(yī)正骨,2015,27(12):73.
[8]蔡云仙.圍手術期耳穴按壓聯(lián)合平衡針療法 在全膝關節(jié)置換術后鎮(zhèn)痛中的應用[J].中醫(yī)正骨,2015,27(06):41.
[9]張榮,王健.人工全膝關節(jié)置換術的圍手術期心理護理[J].中醫(yī)正骨,2015,27(05):77.
[10]喻長純,楊明路,王戰(zhàn)朝.不同手術方式治療脛骨平臺骨折畸形愈合的體會[J].中醫(yī)正骨,2015,27(03):37.
[11]孟維娜,明立功,王新德,等.關節(jié)鏡下清理聯(lián)合腓骨近1/3段截骨治療膝骨關節(jié)炎[J].中醫(yī)正骨,2015,27(11):40.
[12]明立功,孟維娜,王新德,等.腓骨近端截骨治療內(nèi)側間室膝骨關節(jié)炎的近期療效觀察[J].中醫(yī)正骨,2015,27(10):25.
[13]張杰,王人彥,張玉柱.膝骨關節(jié)炎的治療進展[J].中醫(yī)正骨,2015,27(10):68.
[14]梁朝,蔡靜怡,閆立,等.針刀療法改善膝骨關節(jié)炎早期疼痛癥狀的療效評價[J].中醫(yī)正骨,2015,27(09):9.
　LIANG Zhao,CAI Jingyi,YAN Li,et al.Evaluation of the curative effect of needle-knife therapy for relieving knee pain in patients with early knee osteoarthritis[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2015,27(07):9.
[15]王建武,黨建軍,李強,等.四聯(lián)療法治療膝骨關節(jié)炎[J].中醫(yī)正骨,2015,27(08):44.
[16]劉紅娟,郭會利,郭樹農(nóng).云克聯(lián)合中藥治療膝骨關節(jié)炎的護理[J].中醫(yī)正骨,2015,27(08):75.
[17]陳衛(wèi)衡.探索建立系統(tǒng)的膝骨關節(jié)炎中醫(yī)臨床科研范式 和理論體系[J].中醫(yī)正骨,2015,27(07):1.
[18]帥波,沈霖,楊艷萍,等.加味青娥丸治療膝骨關節(jié)炎的作用機制研究[J].中醫(yī)正骨,2015,27(07):15.
　SHUAI Bo,SHEN Lin,YANG Yanping,et al.Study on the mechanism of action of Jiawei Qing'e Wan(加味青娥丸)for the treatment of knee osteoarthritis[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2015,27(07):15.
[19]梅其杰,袁長深,段戡,等.壯藥骨痹方燙熨聯(lián)合運動療法治療膝骨關節(jié)炎的臨床研究[J].中醫(yī)正骨,2015,27(07):27.
　MEI Qijie,YUAN Changshen,DUAN Kan,et al.Clinical study of the curative effect of hot compressing and rubbing with packet of Gubi Fang(骨痹方)combined with exercise therapy in the treatment of knee osteoarthritis[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2015,27(07):27.
[20]王丹輝,張燕,劉麗娟,等.重組人Ⅱ型腫瘤壞死因子受體-抗體融合蛋白 關節(jié)腔注射聯(lián)合中藥薰洗治療膝骨關節(jié)炎的臨床研究[J].中醫(yī)正骨,2015,27(07):31.
　WANG Danhui,ZHANG Yan,LIU Lijuan,et al.Clinical study on intra-articular injection of TypeⅡrecombinant human tumor necrosis factor receptor-Fc fusion protein combined with Chinese herbal steaming and washing therapy for treatment of knee osteoarthritis[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2015,27(07):31.

備注/Memo

備注/Memo:
基金項目:廣西中醫(yī)藥適宜技術開發(fā)與推廣項目(GZSY21-78) 通訊作者:歐志學 E-mail:[email protected]
更新日期/Last Update: 1900-01-01