皮瓣缺血再灌注损伤相关细胞信号通路总结
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摘要
查阅万方数据库及Pubmed数据库2005至2017年间相关文献,中文关键词为"皮瓣缺血再灌注损伤,信号通路,凋亡,氧化应激,炎症反应,微循环,钙超载",英文关键词为"ischemia and reperfusion of skin flap,signal pathway,apoptosis,oxidative stress,inflammatory reaction,microcirculation,calcium overload",依据纳入排除标准选出35篇。最终选用36篇文献进行分析、总结皮瓣IR过程中相关的细胞信号通路。发现目前与缺血再灌注损伤的信号通路主要有:PI3K/Akt、Nrf2/Keap1-ARE、JAK/STAT、p38 MAPK/IKK/NF-κB、Toll4/NF-κB、PHD-HIF、Trx-1-ASK-MAPK、Trx-MKK4-NF-κB、FOXO-c AMP-PKA-CREB-PGC1α、ROS-ASK1-MKK4/MKK7-JNK、Wnt、c-Jun、PKC-ERKs、HIF-1α/VEGF、Akt/c-myc/VEGF等。可从IR发生、发展的一系列病理生理过程相关的信号转导通路层面出发,预防或减轻皮瓣IR,但IR是一个多因素、多信号调节的病理生理过程,仍存有许多疑问,未来对IR相关细胞信号通路更深入研究将为预防和减轻缺血再灌注提供新的靶点。
Access to the Wanfang database and the Pubmed database for relevant articles published from 2005 to 2017 using the keywords of "ischemia and reperfusion of skin flap,signal pathway,apoptosis,oxidative stress,inflammatory reaction,microcirculation,calcium overload" in Chinese and English, respectively. According to inclusion and exclusion criteria, 35 articles were selected.Finally, 36 articles were selected to analyze and summarize the related cellular signaling pathways during the ischemiareperfusion injury of the skin flap. We found that, it is believed that the signaling pathways associated with ischemia-reperfusion injury of skin flap are mainly: PI3 K/Akt、Nrf2/Keap1-ARE、JAK/STAT、p38 MAPK/IKK/NF-κB、Toll4/NF-κB、PHD-HIF、Trx-1-ASK-MAPK、Trx-MKK4-NF-κB、FOXO-c AMP-PKA-CREB-PGC1α、ROS-ASK1-MKK4/MKK7-JNK、Wnt、c-Jun、PKC-ERKs、HIF-1α/VEGF、Akt/c-myc/VEGF. We can prevent or mitigate the ischemia-reperfusion injury of flap from the level of signal transduction pathway related to a series of pathophysiological processes that occur and develop in IR. IR is a pathophysiological process which affected by many factors and involved a variety of molecular mechanisms regulation, but there are still some questions. Further research on IR related cell signaling pathway will provide new targets for prevention and reduction of ischemia reperfusion injury of skin flap.
Access to the Wanfang database and the Pubmed database for relevant articles published from 2005 to 2017 using the keywords of "ischemia and reperfusion of skin flap,signal pathway,apoptosis,oxidative stress,inflammatory reaction,microcirculation,calcium overload" in Chinese and English, respectively. According to inclusion and exclusion criteria, 35 articles were selected.Finally, 36 articles were selected to analyze and summarize the related cellular signaling pathways during the ischemiareperfusion injury of the skin flap. We found that, it is believed that the signaling pathways associated with ischemia-reperfusion injury of skin flap are mainly: PI3 K/Akt、Nrf2/Keap1-ARE、JAK/STAT、p38 MAPK/IKK/NF-κB、Toll4/NF-κB、PHD-HIF、Trx-1-ASK-MAPK、Trx-MKK4-NF-κB、FOXO-c AMP-PKA-CREB-PGC1α、ROS-ASK1-MKK4/MKK7-JNK、Wnt、c-Jun、PKC-ERKs、HIF-1α/VEGF、Akt/c-myc/VEGF. We can prevent or mitigate the ischemia-reperfusion injury of flap from the level of signal transduction pathway related to a series of pathophysiological processes that occur and develop in IR. IR is a pathophysiological process which affected by many factors and involved a variety of molecular mechanisms regulation, but there are still some questions. Further research on IR related cell signaling pathway will provide new targets for prevention and reduction of ischemia reperfusion injury of skin flap.
引文
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[14]Sheng B,Al E.Impaired mitochondrial biogenesis contributes to mitochondrial dysfunction in Alzheimer's disease.Journal of Neurochemistry,2012,120(3):419–429.
[15]Wang J,Min P,Grassetti L,et al.Preliminary Outcomes of Distal IMAP and SEAP Flaps for the Treatment of Unstable Keloids Subject to Recurrent Inflammation and Infections in the Lower Sternal and Upper Abdominal Areas.Journal of Reconstructive Microsurgery,2015,31(09):621-630.
[16]Toni L G B D,Menaldo D L,Cintra A C O,et al.Inflammatory mediators involved in the paw edema and hyperalgesia induced by Batroxase,a metalloproteinase isolated from Bothrops atrox,snake venom.International Immunopharmacology,2015,28(1):199.
[17]Du W,Wu P F,Qing L M,et al.Systemic and flap inflammatory response associates with thrombosis in flap venous crisis.Inflammation,2015,38(1):298-304.
[18]Ruth D,Moul D,Vummidigiridhar P,et al.My D88-dependent and independent pathways of Toll-Like Receptors are engaged in biological activity of Triptolide in ligand-stimulated macrophages.Bmc Chemical Biology,2010,10(1):3-16.
[19]Guo J,Friedman S L.Toll-like receptor 4 signaling in liver injury and hepatic fibrogenesis.Fibrogenesis&Tissue Repair,2010,3(1):21-39.
[20]Chen G Y,Nu?ez G.Sterile inflammation:sensing and reacting to damage.Nature Reviews Immunology,2010,10(12):826-837.
[21]陈拓,王荣春,林仕彬,等.抑制P38MAPK对皮瓣缺血再灌注损伤过程中炎症因子、细胞凋亡的影响.海南医学院学报,2017,23(5):577-580.
[22]Liu P,Pan X,Yin G.Natural Hirudin Increases Rat Flap Viability by Anti-Inflammation via PARs/p38/NF-κB Pathway.Biomed Research International,2015,2015(12):1-7.
[23]Bai M,Liu Y,Yin D,et al.Inhibition of c-Jun N-terminal kinase signaling suppresses skin flap apoptosis in a rat ischemia and/or reperfusion model.Journal of Surgical Research,2016,206(2):337.
[24]Gao W,Qiao X,Ma S,et al.Adipose-derived stem cells accelerate neovascularization in ischaemic diabetic skin flap via expression of hypoxia-inducible factor-1α.Journal of Cellular&Molecular Medicine,2011,15(12):2575-2585.
[25]Froehlich H,Gulati R,Boilson B,et al.Carotid repair using autologous adipose-derived endothelial cells.Stroke,2009,40(5):1886.
[26]Grewal N,Yacomotti L,Melkonyan V,et al.Freezing Adipose Tissue Grafts May Damage Their Ability to Integrate into the Host.Connective Tissue Research,2009,50(1):14-28.
[27]Song S H,Lee M O,Lee J S,et al.Genetic modification of human adipose-derived stem cells for promoting wound healing.Journal of Dermatological Science,2012,66(2):98-107.
[28]Xu Z,Wu L,Sun Y,et al.Tanshinone IIA pretreatment protects free flaps against hypoxic injury by upregulating stem cell-related biomarkers in epithelial skin cells.BMC Complementary and Alternative Medicine,2014,14(1):1-10.
[29]Sareckahujar B,Zak I,Krauze J.Interactions between rs5498polymorphism in the ICAM1 gene and traditional risk factors influence susceptibility to coronary artery disease.Clinical&Experimental Medicine,2009,9(2):117-124.
[30]Min J K,Kim Y M,Kim S W,et al.TNF-related activationinduced cytokine enhances leukocyte adhesiveness:induction of ICAM-1 and VCAM-1 via TNF receptor-associated factor and protein kinase C-dependent NF-kappa B activation in endothelial cells.Journal of Immunology,2005,175(1):531-540.
[31]Phaniendra A,Jestadi D B,Periyasamy L.Free radicals:properties,sources,targets,and their implication in various diseases.Indian Journal of Clinical Biochemistry,2015,30(1):11.
[32]Gong X,Ivanov VN,Hei TK.2,3,5,6-Tetramethylpyrazine(TMP)down-regulated arsenic-induced heme oxygenase-1 and ARS2expression by inhibiting Nrf2,NF-κB,AP-1 and MAPK pathways in human proximal tubular cells.Archives of Toxicology,2016,90(9):1-14.
[33]Adya R,Tan B K,Punn A,et al.Visfatin induces human endothelial VEGF and MMP-2/9 production via MAPK and PI3K/Akt signalling pathways:novel insights into visfatin-induced angiogenesis.[J].Cardiovascular Research,2008,78(2):356-365.
[34]Lim S Y,Davidson S M,Paramanathan A J,et al.The novel adipocytokine visfatin exerts direct cardioprotective effects[J].Journal of Cellular&Molecular Medicine,2008,12(4):1395-1403.
[35]Tsujimoto Y,Croce C M.Analysis of the Structure,Transcripts,and Protein Products of bcl-2,the Gene Involved in Human Follicular Lymphoma[J].Proceedings of the National Academy of Sciences of the United States of America,1986,83(14):5214-5218.
[36]Bajwa N,Liao C,Nikolovskacoleska Z.Inhibitors of the antiapoptotic Bcl-2 proteins:a patent review[J].Expert Opinion on Therapeutic Patents,2012,22(1):37-55.
[2]Mashima R,Okuyama T.The role of lipoxygenases in pathophysiology;new insights and future perspectives.Redox Biology,2015,6:297-310.
[3]Song K,Zhang M,Hu J,et al.Methane-rich saline attenuates ischemia/reperfusion injury of abdominal skin flaps in rats via regulating apoptosis level.BMC Surgery,2015,15(1):92.
[4]Mahmood D F,Abderrazak A,El H K,et al.The thioredoxin system as a therapeutic target in human health and disease.Antioxidants&Redox Signaling,2013,19(11):1266-1303.
[5]Collet J F,Messens J.Structure,function,and mechanism of thioredoxin proteins.Antioxidants&Redox Signaling,2010,13(8):1205-1216
[6]Kundumanisridharan V,Subramani J,Das K C.Thioredoxin Activates MKK4-NFκB Pathway in a Redox-dependent Manner to Control Manganese Superoxide Dismutase Gene Expression in Endothelial Cells.Journal of Biological Chemistry,2015,290:7505-17519..
[7]Kim A,Joseph S,Khan A,et al.Enhanced expression of mitochondrial superoxide dismutase leads to prolonged in vivo cell cycle progression and up-regulation of mitochondrial thioredoxin.Free Radical Biology&Medicine,2010,48(11):1501-1512.
[8]Polvani S,Tarocchi M,Galli A.PPARγand Oxidative Stress:Con(β)Catenating NRF2 and FOXO.Ppar Research,2012,2012(2):641087.
[9]Hristova M,Spiess P C,Kasahara D I,et al.The Tobacco Smoke Component,Acrolein,Suppresses Innate Macrophage Responses by Direct Alkylation of c-Jun N-Terminal Kinase.American Journal of Respiratory Cell&Molecular Biology,2012,46(1):23-33.
[10]Hsu C L,Wu Y L,Tang G J,et al.Ginkgo biloba extract confers protection from cigarette smoke extract-induced apoptosis in human lung endothelial cells:Role of hemeoxygenase-1.Pulmonary Pharmacology&Therapeutics,2009,22(4):286-296.
[11]Goven D,Boutten A,Le?onmalas V,et al.Prolonged cigarette smoke exposure decreases heme oxygenase-1 and alters Nrf2and Bach1 expression in human macrophages:roles of the MAP kinases ERK1/2 and JNK.Febs Letters,2009,583(21):3508-3518.
[12]Webb A E,Brunet A.FOXO transcription factors:key regulators of cellular quality control.Trends in Biochemical Sciences,2014,39(4):159.
[13]Zhao Y,Wang Y,Zhu W G.Applications of post-translational modifications of Fox O family proteins in biological functions.Journal of Molecular Cell Biology,2011,3(5):276-282.
[14]Sheng B,Al E.Impaired mitochondrial biogenesis contributes to mitochondrial dysfunction in Alzheimer's disease.Journal of Neurochemistry,2012,120(3):419–429.
[15]Wang J,Min P,Grassetti L,et al.Preliminary Outcomes of Distal IMAP and SEAP Flaps for the Treatment of Unstable Keloids Subject to Recurrent Inflammation and Infections in the Lower Sternal and Upper Abdominal Areas.Journal of Reconstructive Microsurgery,2015,31(09):621-630.
[16]Toni L G B D,Menaldo D L,Cintra A C O,et al.Inflammatory mediators involved in the paw edema and hyperalgesia induced by Batroxase,a metalloproteinase isolated from Bothrops atrox,snake venom.International Immunopharmacology,2015,28(1):199.
[17]Du W,Wu P F,Qing L M,et al.Systemic and flap inflammatory response associates with thrombosis in flap venous crisis.Inflammation,2015,38(1):298-304.
[18]Ruth D,Moul D,Vummidigiridhar P,et al.My D88-dependent and independent pathways of Toll-Like Receptors are engaged in biological activity of Triptolide in ligand-stimulated macrophages.Bmc Chemical Biology,2010,10(1):3-16.
[19]Guo J,Friedman S L.Toll-like receptor 4 signaling in liver injury and hepatic fibrogenesis.Fibrogenesis&Tissue Repair,2010,3(1):21-39.
[20]Chen G Y,Nu?ez G.Sterile inflammation:sensing and reacting to damage.Nature Reviews Immunology,2010,10(12):826-837.
[21]陈拓,王荣春,林仕彬,等.抑制P38MAPK对皮瓣缺血再灌注损伤过程中炎症因子、细胞凋亡的影响.海南医学院学报,2017,23(5):577-580.
[22]Liu P,Pan X,Yin G.Natural Hirudin Increases Rat Flap Viability by Anti-Inflammation via PARs/p38/NF-κB Pathway.Biomed Research International,2015,2015(12):1-7.
[23]Bai M,Liu Y,Yin D,et al.Inhibition of c-Jun N-terminal kinase signaling suppresses skin flap apoptosis in a rat ischemia and/or reperfusion model.Journal of Surgical Research,2016,206(2):337.
[24]Gao W,Qiao X,Ma S,et al.Adipose-derived stem cells accelerate neovascularization in ischaemic diabetic skin flap via expression of hypoxia-inducible factor-1α.Journal of Cellular&Molecular Medicine,2011,15(12):2575-2585.
[25]Froehlich H,Gulati R,Boilson B,et al.Carotid repair using autologous adipose-derived endothelial cells.Stroke,2009,40(5):1886.
[26]Grewal N,Yacomotti L,Melkonyan V,et al.Freezing Adipose Tissue Grafts May Damage Their Ability to Integrate into the Host.Connective Tissue Research,2009,50(1):14-28.
[27]Song S H,Lee M O,Lee J S,et al.Genetic modification of human adipose-derived stem cells for promoting wound healing.Journal of Dermatological Science,2012,66(2):98-107.
[28]Xu Z,Wu L,Sun Y,et al.Tanshinone IIA pretreatment protects free flaps against hypoxic injury by upregulating stem cell-related biomarkers in epithelial skin cells.BMC Complementary and Alternative Medicine,2014,14(1):1-10.
[29]Sareckahujar B,Zak I,Krauze J.Interactions between rs5498polymorphism in the ICAM1 gene and traditional risk factors influence susceptibility to coronary artery disease.Clinical&Experimental Medicine,2009,9(2):117-124.
[30]Min J K,Kim Y M,Kim S W,et al.TNF-related activationinduced cytokine enhances leukocyte adhesiveness:induction of ICAM-1 and VCAM-1 via TNF receptor-associated factor and protein kinase C-dependent NF-kappa B activation in endothelial cells.Journal of Immunology,2005,175(1):531-540.
[31]Phaniendra A,Jestadi D B,Periyasamy L.Free radicals:properties,sources,targets,and their implication in various diseases.Indian Journal of Clinical Biochemistry,2015,30(1):11.
[32]Gong X,Ivanov VN,Hei TK.2,3,5,6-Tetramethylpyrazine(TMP)down-regulated arsenic-induced heme oxygenase-1 and ARS2expression by inhibiting Nrf2,NF-κB,AP-1 and MAPK pathways in human proximal tubular cells.Archives of Toxicology,2016,90(9):1-14.
[33]Adya R,Tan B K,Punn A,et al.Visfatin induces human endothelial VEGF and MMP-2/9 production via MAPK and PI3K/Akt signalling pathways:novel insights into visfatin-induced angiogenesis.[J].Cardiovascular Research,2008,78(2):356-365.
[34]Lim S Y,Davidson S M,Paramanathan A J,et al.The novel adipocytokine visfatin exerts direct cardioprotective effects[J].Journal of Cellular&Molecular Medicine,2008,12(4):1395-1403.
[35]Tsujimoto Y,Croce C M.Analysis of the Structure,Transcripts,and Protein Products of bcl-2,the Gene Involved in Human Follicular Lymphoma[J].Proceedings of the National Academy of Sciences of the United States of America,1986,83(14):5214-5218.
[36]Bajwa N,Liao C,Nikolovskacoleska Z.Inhibitors of the antiapoptotic Bcl-2 proteins:a patent review[J].Expert Opinion on Therapeutic Patents,2012,22(1):37-55.