TLR4/NF-κB信号转导通路在激素性股骨头坏死防治研究中的应用
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摘要
NF-κB细胞是TOLL细胞亚群的成员,其分化受到多种因子调节并过度刺激TLR4/NF-κB信号转导通路与免疫炎症反应相关。中医药学是在传统中医学的理论的指导下形成的,其活血化瘀、消肿止痛等基本理论与免疫炎症调节机制异曲同工,现代研究也初步揭露了TLR4/NF-κB与中医药分类和调理的相关性。对NF-κB细胞免疫炎症机制进行综述,并对其与中医药相关性进行分析,以期对激素性股骨头坏死形成、发展和调理的微观机制研究有所指导。
NF-κB cells are members of TOLL cell subpopulations, and their differentiation is regulated by various factors and over-stimulation of TLR4/NF-κB signal transduction pathway is associated with immune inflammatory response. Traditional Chinese administration is formed under the guidance of the traditional Chinese medicine theory. Its basic theories of blood circulation,blood stasis,swelling and pain relief are similar to those of immuno-inflammatory regulation mechanisms. Modern research also initially revealed the classification and regulation of TLR4/NF-κB and Chinese medicine. This article reviews the mechanism of NF-κB cell immuno-inflammation and analyzes its correlation with traditional Chinese medicine in order to provide the guidance for the study of the microscopic mechanism of necrosis,development and regulation of steroid-induced osteonecrosis of femoral head.
NF-κB cells are members of TOLL cell subpopulations, and their differentiation is regulated by various factors and over-stimulation of TLR4/NF-κB signal transduction pathway is associated with immune inflammatory response. Traditional Chinese administration is formed under the guidance of the traditional Chinese medicine theory. Its basic theories of blood circulation,blood stasis,swelling and pain relief are similar to those of immuno-inflammatory regulation mechanisms. Modern research also initially revealed the classification and regulation of TLR4/NF-κB and Chinese medicine. This article reviews the mechanism of NF-κB cell immuno-inflammation and analyzes its correlation with traditional Chinese medicine in order to provide the guidance for the study of the microscopic mechanism of necrosis,development and regulation of steroid-induced osteonecrosis of femoral head.
引文
[1] Joaquin Moya-Angeler,Arianna L Gianakos,Jordan C Villa,等.Current concepts on osteonecrosis of the femoral head[J].世界骨科杂志:英文版,2015(8):590-601.
[2] Arbab D,K?nig DP.Atraumatic Femoral Head Necrosis in Adults[J].Deutsches ?rzteblatt International,2016,113(3):31.
[3] 陈宝琅.激素性股骨头坏死发病机制中细胞凋亡的研究进展[J].中国当代医药,2016(19):12-15.
[4] 刘熹,李钊伟,唐宝明,等.激素性股骨头坏死的发病机制中骨髓间充质干细胞成脂分化的最新进展[J].中医药,2017(2):26-27.
[5] Zheng L,Wang W,Ni J,et al.The Association of eNOS Gene Polymorphism with Avascular Necrosis of Femoral Head[J].Plos One,2014,9(2):e87583.
[6] Tian L,Wen Q,Dang X,et al.Immune response associated with Toll-like receptor 4 signaling pathway leads to steroid-induced femoral head osteonecrosis[J].Bmc Musculoskelet Disord,2014,15(1):1-12.
[7] Zeng X,Zhan K,Zhang L,et al.The impact of high total cholesterol and high low-density lipoprotein on avascular necrosis of the femoral head in low-energy femoral neck fractures[J].Journal of Orthopaedic Surgery & Research,2017,12(1):30.
[8] Kumar MN,Belehalli P,Ramachandra P.PET/CT study of temporal variations in blood flow to the femoral head following low-energy fracture of the femoral neck[J].Orthopedics,2014,37(6):e563-570.
[9] Wang G,Zhang CQ,Sun Y,et al.Changes in femoral head blood supply and vascular endothelial growth factor in rabbits with steroid-induced osteonecrosis[J].Journal of International Medical Research,2010,38(3):1060-1069.
[10] Mukisi MM,Bashoun K,Burny F.Sickle-cell hip necrosis and intraosseous pressure[J].Orthopaedics & Traumatology Surgery & Research Otsr,2009,95(2):134.
[11] Jilka RL,Noble B,Weinstein RS.OSTEOCYTE APOPTOSIS[J].Bone,2013,54(2):264.
[12] Nozaki Y,Kumagai K,Miyata N,et al.Pravastatin reduces steroid-induced osteonecrosis of the femoral head in SHRSP rats[J].Acta Orthopaedica,2012,83(1):87-92.
[13] Jiang Y,Zhang Y,Zhang H,et al.Pravastatin prevents steroid-induced osteonecrosis in rats by suppressing PPARγ expression and activating Wnt signaling pathway[J].Experimental Biology & Medicine,2014,239(3):347.
[14] Li J,Wang Y,Li Y,et al.The effect of combined regulation of the expression of peroxisome proliferator-activated receptor-γ and calcitonin gene-related peptide on alcohol-induced adipogenic differentiation of bone marrow mesenchymal stem cells[J].Molecular & Cellular Biochemistry,2014,392(1-2):39-48.
[15] Beckmann R,Shaheen H,Kweider N,et al.Enoxaparin prevents steroid-related avascular necrosis of the femoral head[J].The scientific world journal,2014,2014(3):347813.
[16] Li J,Fan L,Yu Z,et al.The effect of deferoxamine on angiogenesis and bone repair in steroid-induced osteonecrosis of rabbit femoral heads.[J].Experimental Biology & Medicine,2015,240(2):273-280.
[17] Stallone G,Infante B,Grandaliano G.Management and prevention of post-transplant malignancies in kidney transplant recipients[J].2015,8(5):637-644.
[18] Chen N,Qian J,Chen J,et al.Phase 2 studies of oral hypoxia-inducible factor prolyl hydroxylase inhibitor FG-4592 for treatment of anemia in China[J].Nephrology,dialysis,transplantation :official publication of the European Dialysis and Transplant Association - European Renal Association,2017,32(8).
[19] Xue XH,Feng ZH,Li ZX,et al.Salidroside inhibits steroid-induced avascular necrosis of the femoral head via the PI3K/Akt signaling pathway:In vitro and in vivo studies[J].Molecular Medicine Reports,2018,17(3):3751-3757.
[20] Jiang Y,Zhang Y,Chen W,et al.Achyranthes bidentata extract exerts osteoprotective effects on steroid-induced osteonecrosis of the femoral head in rats by regulating RANKL/RANK/OPG signaling[J].Journal of Translational Medicine,2014,12(1):334.
[21] Youm YS,Lee SY,Lee SH.Apoptosis in the osteonecrosis of the femoral head[J].Clin Orthop Surg,2010,2(4):250-255.
[22] Robinson WH.Desethylhydroxychloroquine for the treatment of diseases associated with inflammation[J].2018.
[23] Brown J,Wang H,Hajishengallis GN,et al.Critical Reviews in Oral Biology & Medicine:TLR-signaling Networks:An Integration of Adaptor Molecules,Kinases,and Cross-talk[J].Journal of Dental Research,2011,90(4):417-427.
[24] Wu J,Wu H,An J,et al.Critical role of integrin CD11c in splenic dendritic cell capture of missing-self CD47 cells to induce adaptive immunity[J].Proc Natl Acad Sci USA,2018.
[25] Lin QQ,Geng YW,Jiang ZW,et al.SIRT1 regulates lipopolysaccharide-induced CD40 expression in renal medullary collecting duct cells by suppressing the TLR4-NF-κB signaling pathway[J].Life Sciences,2016,170:100.
[26] Prüfer S,Weber M,Sasca D,et al.Distinct Signaling Cascades of TREM-1,TLR and NLR in Neutrophils and Monocytic Cells[J].Journal of Innate Immunity,2014,6(3):339-352.
[27] Hou Y,Lu X,Zhang Y.IRAK Inhibitor Protects the Intestinal Tract of Necrotizing Enterocolitis by Inhibiting the Toll-Like Receptor (TLR) Inflammatory Signaling Pathway in Rats[J].Medical Science Monitor International Medical Journal of Experimental & Clinical Research,2018,24:3366-3373.
[28] Griffioen K,Mattson MP,Okun E.Deficiency of Toll-like receptors 2,3 or 4 extends life expectancy in Huntington’s disease mice[J].Heliyon,2018,4(1):e00508.
[29] 忻寅强.热休克蛋白27(HSP27)的磷酸化通过影响Toll样受体4(TLR4)的转运调控下游炎症信号通路[D].南京:南京师范大学,2013.
[30] 覃万翔,罗敏,石英,等.双氢青蒿素抑制LPS诱导的小胶质细胞炎症反应[J].第三军医大学学报,2017,39(22):2189-2194.
[31] Moya FB,Pineda Galindo LF,García d l PM.Impact of Chronic Glucocorticoid Treatment on Cardiovascular Risk Profile in Patients with Systemic Lupus Erythematosus[J].Journal of Clinical Rheumatology Practical Reports on Rheumatic & Musculoskeletal Diseases,2016,22(1):8.
[32] Yang X,Chen GT,Wang YQ,et al.TLR4 promotes the expression of HIF-1α by triggering reactive oxygen species in cervical cancer cellsin vitro-implications for therapeutic intervention[J].Molecular Medicine Reports,2018,17(2):2229.
[33] 王诗源,刘巍,李大可,等.清热化浊降酸方对急性痛风性关节炎患者血清IL-1β、IL-6、IL-8水平的影响[J].山东医药,2018(2):93-95.
[34] 杜津莉,樊炜骏,李建,等.独活寄生汤含药血清对膝关节OA大鼠滑膜细胞TNF-α、IL-6、IL-8、IL-10表达的影响及其机制[J].山东医药,2017(44):14-17.
[35] 魏文元,武永利,李春,等.四逆汤饼灸对兔膝关节退变模型血清中IL-1、IL-6和TNF-α水平的影响[J].辽宁中医杂志,2017,44(3):615-617.
[36] 严国鸿,张玉琴,林雄,等.双藤痹痛凝胶膏剂对胶原诱导性关节炎模型大鼠血浆炎性因子和滑膜组织相关因子的影响[J].中国中医药信息杂志,2018(1):43-47.
[37] Vch F,Mouzopoulos G,Floros T,et al.Steroid-induced femoral head osteonecrosis in immune thrombocytopenia treatment with osteochondral autograft transplantation[J].Knee Surgery Sports Traumatology Arthroscopy Official Journal of the Esska,2015,23(9):2605.
[38] Adapala NS,Yamaguchi R,Phipps M,et al.Necrotic Bone Stimulates Proinflammatory Responses in Macrophages through the Activation of Toll-Like Receptor 4[J].American Journal of Pathology,2016,186(11):2987-2999.
[39] Zhao HX,Huang YX,Tao JG.ST1926 Attenuates Steroid‐Induced Osteoporosis in Rats by Inhibiting Inflammation Response[J].Journal of Cellular Biochemistry,2017,118(8).
[40] Ihn HJ,Ju AK,Cho HS,et al.Diphlorethohydroxycarmalol from Ishige okamurae Suppresses Osteoclast Differentiation by Downregulating the NF-κB Signaling Pathway[J].International Journal of Molecular Sciences,2017,18(12):2635.
[41] Pei J,Fan L,Nan K,et al.Excessive Activation of TLR4/NF-κB Interactively Suppresses the Canonical Wnt/β-catenin Pathway and Induces SANFH in SD Rats[J].Sci Rep,2017,7(1):11928.
[42] 曾平,梁景超.蛋白质组学技术在股骨头坏死诊治中的应用进展[J].山东医药,2014(18):95-96.
[43] Tse SM,Mok CC.Time trend and risk factors of avascular bone necrosis in patients with systemic lupus erythematosus[J].Lupus,2017,26(7):715-722.
[44] 高美娟.成人股骨头坏死ANFH的X线与CT征象及临床价值[J].临床医药文献电子杂志,2018(16):113-114.
[45] Wang F,Wang Y,Hu N,et al.RISK-FACTORS,PATHOGENESIS,AND PHARMACEUTICAL APPROACHES FOR TREATMENT OF STEROID-INDUCED BONE INFARCTION OF FEMORAL HEAD[J].Acta Poloniae Pharmaceutica,2016,73(3):557-563.
[46] Bailey JN,Pericakvance MA,Haines JL.The impact of the human genome project on complex disease[J].Genes,2014,5(3):518.
[47] Gao W,Xiong Y,Li Q.Inhibition of Toll-Like Receptor Signaling as a Promising Therapy for Inflammatory Diseases:A Journey from Molecular to Nano Therapeutics[J].Frontiers in physiology,2017(8):508.
[2] Arbab D,K?nig DP.Atraumatic Femoral Head Necrosis in Adults[J].Deutsches ?rzteblatt International,2016,113(3):31.
[3] 陈宝琅.激素性股骨头坏死发病机制中细胞凋亡的研究进展[J].中国当代医药,2016(19):12-15.
[4] 刘熹,李钊伟,唐宝明,等.激素性股骨头坏死的发病机制中骨髓间充质干细胞成脂分化的最新进展[J].中医药,2017(2):26-27.
[5] Zheng L,Wang W,Ni J,et al.The Association of eNOS Gene Polymorphism with Avascular Necrosis of Femoral Head[J].Plos One,2014,9(2):e87583.
[6] Tian L,Wen Q,Dang X,et al.Immune response associated with Toll-like receptor 4 signaling pathway leads to steroid-induced femoral head osteonecrosis[J].Bmc Musculoskelet Disord,2014,15(1):1-12.
[7] Zeng X,Zhan K,Zhang L,et al.The impact of high total cholesterol and high low-density lipoprotein on avascular necrosis of the femoral head in low-energy femoral neck fractures[J].Journal of Orthopaedic Surgery & Research,2017,12(1):30.
[8] Kumar MN,Belehalli P,Ramachandra P.PET/CT study of temporal variations in blood flow to the femoral head following low-energy fracture of the femoral neck[J].Orthopedics,2014,37(6):e563-570.
[9] Wang G,Zhang CQ,Sun Y,et al.Changes in femoral head blood supply and vascular endothelial growth factor in rabbits with steroid-induced osteonecrosis[J].Journal of International Medical Research,2010,38(3):1060-1069.
[10] Mukisi MM,Bashoun K,Burny F.Sickle-cell hip necrosis and intraosseous pressure[J].Orthopaedics & Traumatology Surgery & Research Otsr,2009,95(2):134.
[11] Jilka RL,Noble B,Weinstein RS.OSTEOCYTE APOPTOSIS[J].Bone,2013,54(2):264.
[12] Nozaki Y,Kumagai K,Miyata N,et al.Pravastatin reduces steroid-induced osteonecrosis of the femoral head in SHRSP rats[J].Acta Orthopaedica,2012,83(1):87-92.
[13] Jiang Y,Zhang Y,Zhang H,et al.Pravastatin prevents steroid-induced osteonecrosis in rats by suppressing PPARγ expression and activating Wnt signaling pathway[J].Experimental Biology & Medicine,2014,239(3):347.
[14] Li J,Wang Y,Li Y,et al.The effect of combined regulation of the expression of peroxisome proliferator-activated receptor-γ and calcitonin gene-related peptide on alcohol-induced adipogenic differentiation of bone marrow mesenchymal stem cells[J].Molecular & Cellular Biochemistry,2014,392(1-2):39-48.
[15] Beckmann R,Shaheen H,Kweider N,et al.Enoxaparin prevents steroid-related avascular necrosis of the femoral head[J].The scientific world journal,2014,2014(3):347813.
[16] Li J,Fan L,Yu Z,et al.The effect of deferoxamine on angiogenesis and bone repair in steroid-induced osteonecrosis of rabbit femoral heads.[J].Experimental Biology & Medicine,2015,240(2):273-280.
[17] Stallone G,Infante B,Grandaliano G.Management and prevention of post-transplant malignancies in kidney transplant recipients[J].2015,8(5):637-644.
[18] Chen N,Qian J,Chen J,et al.Phase 2 studies of oral hypoxia-inducible factor prolyl hydroxylase inhibitor FG-4592 for treatment of anemia in China[J].Nephrology,dialysis,transplantation :official publication of the European Dialysis and Transplant Association - European Renal Association,2017,32(8).
[19] Xue XH,Feng ZH,Li ZX,et al.Salidroside inhibits steroid-induced avascular necrosis of the femoral head via the PI3K/Akt signaling pathway:In vitro and in vivo studies[J].Molecular Medicine Reports,2018,17(3):3751-3757.
[20] Jiang Y,Zhang Y,Chen W,et al.Achyranthes bidentata extract exerts osteoprotective effects on steroid-induced osteonecrosis of the femoral head in rats by regulating RANKL/RANK/OPG signaling[J].Journal of Translational Medicine,2014,12(1):334.
[21] Youm YS,Lee SY,Lee SH.Apoptosis in the osteonecrosis of the femoral head[J].Clin Orthop Surg,2010,2(4):250-255.
[22] Robinson WH.Desethylhydroxychloroquine for the treatment of diseases associated with inflammation[J].2018.
[23] Brown J,Wang H,Hajishengallis GN,et al.Critical Reviews in Oral Biology & Medicine:TLR-signaling Networks:An Integration of Adaptor Molecules,Kinases,and Cross-talk[J].Journal of Dental Research,2011,90(4):417-427.
[24] Wu J,Wu H,An J,et al.Critical role of integrin CD11c in splenic dendritic cell capture of missing-self CD47 cells to induce adaptive immunity[J].Proc Natl Acad Sci USA,2018.
[25] Lin QQ,Geng YW,Jiang ZW,et al.SIRT1 regulates lipopolysaccharide-induced CD40 expression in renal medullary collecting duct cells by suppressing the TLR4-NF-κB signaling pathway[J].Life Sciences,2016,170:100.
[26] Prüfer S,Weber M,Sasca D,et al.Distinct Signaling Cascades of TREM-1,TLR and NLR in Neutrophils and Monocytic Cells[J].Journal of Innate Immunity,2014,6(3):339-352.
[27] Hou Y,Lu X,Zhang Y.IRAK Inhibitor Protects the Intestinal Tract of Necrotizing Enterocolitis by Inhibiting the Toll-Like Receptor (TLR) Inflammatory Signaling Pathway in Rats[J].Medical Science Monitor International Medical Journal of Experimental & Clinical Research,2018,24:3366-3373.
[28] Griffioen K,Mattson MP,Okun E.Deficiency of Toll-like receptors 2,3 or 4 extends life expectancy in Huntington’s disease mice[J].Heliyon,2018,4(1):e00508.
[29] 忻寅强.热休克蛋白27(HSP27)的磷酸化通过影响Toll样受体4(TLR4)的转运调控下游炎症信号通路[D].南京:南京师范大学,2013.
[30] 覃万翔,罗敏,石英,等.双氢青蒿素抑制LPS诱导的小胶质细胞炎症反应[J].第三军医大学学报,2017,39(22):2189-2194.
[31] Moya FB,Pineda Galindo LF,García d l PM.Impact of Chronic Glucocorticoid Treatment on Cardiovascular Risk Profile in Patients with Systemic Lupus Erythematosus[J].Journal of Clinical Rheumatology Practical Reports on Rheumatic & Musculoskeletal Diseases,2016,22(1):8.
[32] Yang X,Chen GT,Wang YQ,et al.TLR4 promotes the expression of HIF-1α by triggering reactive oxygen species in cervical cancer cellsin vitro-implications for therapeutic intervention[J].Molecular Medicine Reports,2018,17(2):2229.
[33] 王诗源,刘巍,李大可,等.清热化浊降酸方对急性痛风性关节炎患者血清IL-1β、IL-6、IL-8水平的影响[J].山东医药,2018(2):93-95.
[34] 杜津莉,樊炜骏,李建,等.独活寄生汤含药血清对膝关节OA大鼠滑膜细胞TNF-α、IL-6、IL-8、IL-10表达的影响及其机制[J].山东医药,2017(44):14-17.
[35] 魏文元,武永利,李春,等.四逆汤饼灸对兔膝关节退变模型血清中IL-1、IL-6和TNF-α水平的影响[J].辽宁中医杂志,2017,44(3):615-617.
[36] 严国鸿,张玉琴,林雄,等.双藤痹痛凝胶膏剂对胶原诱导性关节炎模型大鼠血浆炎性因子和滑膜组织相关因子的影响[J].中国中医药信息杂志,2018(1):43-47.
[37] Vch F,Mouzopoulos G,Floros T,et al.Steroid-induced femoral head osteonecrosis in immune thrombocytopenia treatment with osteochondral autograft transplantation[J].Knee Surgery Sports Traumatology Arthroscopy Official Journal of the Esska,2015,23(9):2605.
[38] Adapala NS,Yamaguchi R,Phipps M,et al.Necrotic Bone Stimulates Proinflammatory Responses in Macrophages through the Activation of Toll-Like Receptor 4[J].American Journal of Pathology,2016,186(11):2987-2999.
[39] Zhao HX,Huang YX,Tao JG.ST1926 Attenuates Steroid‐Induced Osteoporosis in Rats by Inhibiting Inflammation Response[J].Journal of Cellular Biochemistry,2017,118(8).
[40] Ihn HJ,Ju AK,Cho HS,et al.Diphlorethohydroxycarmalol from Ishige okamurae Suppresses Osteoclast Differentiation by Downregulating the NF-κB Signaling Pathway[J].International Journal of Molecular Sciences,2017,18(12):2635.
[41] Pei J,Fan L,Nan K,et al.Excessive Activation of TLR4/NF-κB Interactively Suppresses the Canonical Wnt/β-catenin Pathway and Induces SANFH in SD Rats[J].Sci Rep,2017,7(1):11928.
[42] 曾平,梁景超.蛋白质组学技术在股骨头坏死诊治中的应用进展[J].山东医药,2014(18):95-96.
[43] Tse SM,Mok CC.Time trend and risk factors of avascular bone necrosis in patients with systemic lupus erythematosus[J].Lupus,2017,26(7):715-722.
[44] 高美娟.成人股骨头坏死ANFH的X线与CT征象及临床价值[J].临床医药文献电子杂志,2018(16):113-114.
[45] Wang F,Wang Y,Hu N,et al.RISK-FACTORS,PATHOGENESIS,AND PHARMACEUTICAL APPROACHES FOR TREATMENT OF STEROID-INDUCED BONE INFARCTION OF FEMORAL HEAD[J].Acta Poloniae Pharmaceutica,2016,73(3):557-563.
[46] Bailey JN,Pericakvance MA,Haines JL.The impact of the human genome project on complex disease[J].Genes,2014,5(3):518.
[47] Gao W,Xiong Y,Li Q.Inhibition of Toll-Like Receptor Signaling as a Promising Therapy for Inflammatory Diseases:A Journey from Molecular to Nano Therapeutics[J].Frontiers in physiology,2017(8):508.
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