[1]申 震,朱付平,黄 勇,等.Wnt/Ca2+信号通路在肢体缺血/再灌注损伤机制中的研究进展[J].中国药理学通报,2018,(10):1344-1347.[doi:10.3969/j.issn.1001-1978.2018.10.004]
 SHEN Zhen,ZHU Fu-ping,HUANG Yong,et al.Research progress of Wnt/Ca2+ signaling pathway in mechanism of limb ischemia/reperfusion injury[J].Chinese Pharmacological Bulletin,2018,(10):1344-1347.[doi:10.3969/j.issn.1001-1978.2018.10.004]





Research progress of Wnt/Ca2+ signaling pathway in mechanism of limb ischemia/reperfusion injury
申 震1朱付平1黄 勇2范仪铭2周富强1潘成熙1
1.湖南中医药大学第一附属医院骨科,湖南 长沙 410007; 2.河南省洛阳正骨医院骨科,河南 洛阳 471000
SHEN Zhen1 ZHU Fu-ping1 HUANG Yong2 FAN Yi-ming2 ZHOU Fu-qiang1 PAN Cheng-xi1
1.Dept of Orthopedics, the First Affiliated Hospital of Hunan University of Chinese Medicine,Changsha 410007,China; 2.Dept of Orthopedics, Luoyang Orthopedic Hospital of Henan Province, Luoyang 471000,China
Wnt/Ca2+信号通路 细胞凋亡 Ca2+超载 炎症反应 肢体缺血/再灌注损伤 病理机制
Wnt/Ca2+ signaling pathway apoptosis calcium ion overload inflammatory response limb ischemia/reperfusion injury pathological mechanism
R-05; R329.25; R348.1; R364.5; R619.9
Wnt/Ca2+ signaling pathway is an integrant part of non-canonical Wnt signaling, which is closely related with initiation and progression of many pathological changes including apoptosis, calcium ion overload, inflammation and so on.Limb ischemia/reperfusion injury(LIRI)is common in clinical practice and difficult to deal with.The up-regulation of calcium concentration is induced and components sensitive to calcium are activated by Wnt/Ca2+ pathway.Additionally, Wnt/Ca2+-medicated calcium metabolic process and inflammatory responses are involved with LIRI.Therefore, based on literature review, this present paper summarizes the role of Wnt/Ca2+ pathway in the pathological mechanism of LIRI.


[1] K?l?? Y, ?zer A ,,Tatar T,et al.Effect of picroside II on hind limb ischemia reperfusion injury in rats[J].Drug Des Devel Ther,2017,11:1917-25.
[2] Gao X, Bi Y, Chi K, et al.Glycine-nitronyl nitroxide conjugate protects human umbilical vein endothelial cells against hypoxia/reoxygenation injury via multiple mechanisms and ameliorates hind limb ischemia/reperfusion injury in rats[J].Biochem Biophys Res Commun,2017,488:239-46.
[3] Ozturk L,Dogan H T,Kilicarslan A,et al.Effect of different doses of pregabalin on skeletal muscle ischaemia-reperfusion injury in rats[J].Bratisl Lek Listy,2017,118(7):417-22.
[4] Hong Y,Zhang B,Yu L.Cell membrane integrity and revascularization: The possible functional mechanism of ischemic preconditioning for skeletal muscle protection against ischemic-reperfusion injury[J].Acta Histochem,2017,119(3):309-14.
[5] Zong H,Li X,Lin H,et al.Lipoxin A4 pretreatment mitigates skeletal muscle ischemia-reperfusion injury in rats[J].Am J Transl Res,2017,9(3):1139-50.
[6] Cheng Y,Di S,Fan C,et al.SIRT1 activation by pterostilbene attenuates the skeletal muscle oxidative stress injury and mitochondrial dysfunction induced by ischemia reperfusion injury[J].Apoptosis,2016,21:905-16.
[7] Ling H Y,Gray C B,Zambon A C.CamkIIδ mediates myocardial ischemia/reperfusion injury through NF-kappa B[J].Circ Res,2013,112(6):935-44.
[8] Prasad A M,Nuno D W,Koval O M,et al.Differential control of calcium homeostasis and vascular reactivity by Ca2+/calmodulin-dependent kinase II[J].Hypertension,2013,62:434-41.
[9] Grebennikova T A,Belaya Z E,Rozhinskaya L Y.The canonical Wnt/β-catenin pathway: from the history of its discovery to clinical application[J].Ter Arkh,2016,88(10):74-81.
[10] Niehrs C.The complex world of WNT receptor signaling[J].Nat Rev Mol Cell Bio,2012,13(12):767-79.
[11] 吕昕瞳,封 瑞,蔡际群,等.遗传性癫痫大鼠海马组织Ca2+/Cav1.2/CaM/CaMK Ⅱ信号通路的异常变化[J].中国药理学通报,2013,29(1):31-5.
[11] Lyu X T,Feng R,Cai J Q,et al.The abnormal changes of Ca2+/Cavl.2/CaM/CaMK Ⅱ signaling pathway in hippocampus of genetic epileptic rat[J].Chin Phamacol Bull,2013,29(1):31-5.
[12] 雷 明,苏敬阳,李 卓,等.Cav1.2钙离子通道三维结构的同源建模及其应用[J].中国药理学通报,2017,33(1):90-4.
[12] Lei M,Su J Y,Li Z,et al.Homology modeling and application of 3D structure of Cav1.2 channel[J].Chin Phamacol Bull,2017,33(1):90-4.
[13] Wu J P,Yin Z,Li Z Q,et al.Structure of the voltage-gated calcium channel Cav1.1 complex[J].Science,2015,350(6267):aad2395.
[14] 孔令恒,顾晓明,南 瑛,等.钙/钙调蛋白依赖性蛋白激酶II抑制剂KN-93加重大鼠离体心脏钙超载损伤[J].中国药理学通报,2016,32(6):832-6.
[14] Kong L H,Gu X M,Nan Y,et al.Ca2+/calmodulin-dependent protein kinase II inhibitor KN-93 aggravates the calcium paradox-induced heart injury[J].Chin Phamacol Bull,2016,32(6):832-6.
[15] Min D,Guo F,Zhu S,et al.The alterations of Ca2+/calmodulin /CaMKⅡ/Cav1.2 signaling in experimental models of Alzheimer's disease and vascular dementia[J].Neurosci Lett,2013,538:60-5.
[16] Sihgh M V,Swaminathan P D,Luczak E D,et al.MyD88 mediated inflammatory signaling leads to CaMKⅡ oxidation, cardiac hypertrophy and death after myocardial infarction[J].J Mol Cell Cardiol,2012,52(5):1135-44.
[17] Zhao Y,Yang H,Meng K,et al.Probing the Ca2+/CaM-induced secondary structural and conformational changes in calcineurin[J].Int J Biol Macromol,2014,64:453-7.
[18] Paradis S,Charles A L,Meyer A,et al.Chronology of mitochondrial and cellular events during skeletal muscle ischemia-reperfusion[J].Am J Physiol Cell Physiol,2016,310:C968-82.
[19] Schaale K,Neumann J,Schneider D,et al.Wnt signaling in macrophages: augmenting and inhibiting mycobacteria-induced inflammatory responses[J].Eur J Cell Bio1,2011,90:553-9.
[20] Zhao C H,Bu X M,Wang W,et al.GEC-derived SFRP5 inhibits Wnt5a-induced macrophage chemotaxis and activation[J].PLoS One,2014,9(1):e85058.
[21] Iida H,Schmeichel A M,Wang Y,et al.Orchestration of the inflammatory response in ischemia-reperfusion injury[J].J Peripher Nerv Syst,2007,12(2):131-8.
[22] Zeng Q,Fu Q,Wang X,et al.Protective effects of Sonic Hedgehog against ischemia/reperfusion injury in mouse skeletal muscle via AKT/mTOR/p70S6K signaling[J].Cell Physiol Biochem,2017,43(5):1813-28.
[23] Hatoko M,Tanaka A,Kuwahara M,et al.Difference of molecular response to ischemia-reperfusion of rat skeletal muscle as a function of ischemic time; study of the expression of p53, p21(WAF-1),Bax protein, and apoptosis[J].Ann Plast Surg,2002,48(1):68-74.
[24] Davis J,Kwong J Q,Kitsis R N.Apoptosis repressor with a CARD domain(ARC)restrains Bax-mediated pathogenesis in dystrophic skeletal muscle [J].PLoS One,2013,8(12):e82053.
[25] Quindry J C,Miller L,McGinnis G,et al.Ischemia reperfusion injury,KATP channels,and exercise-induced cardioprotection against apoptosis [J].J Appl Physiol(1985),2012,113(3):498-506.


 WANG Jing feng,PANG Long,XUE Yong,et al.Protective effects of polysaccharides, triterpene glycosides and collagen polypeptides from Apostichopus japonicus on vascular endothelial cells[J].Chinese Pharmacological Bulletin,2008,(10):0.
 LI Cai li,WEI Hu lai,SU Hai xiang.Antagonistic effects of N acetylcysteine on the cytotoxicity of arsenic trioxide to lymphocytes[J].Chinese Pharmacological Bulletin,2011,(10):99.
 LIU Yue liang,LUO Jin yong,ZHANG Yan,et al.Role of dihydroartemisinin(DHA) in proliferation and apoptosis of human osteosarcoma 143B cells[J].Chinese Pharmacological Bulletin,2012,(10):1719.
 ZHANG Li-jing,ZHANG Lei-lei,HUANG Wen-hua,et al.Effects of triptonoterpene methyl ether on proliferation and apoptosis of human gastric adenocarcinoma AGS cells[J].Chinese Pharmacological Bulletin,2014,(10):1066.
[5]陈钟琳,姜红岩,洪晓冰,等.hi FGF2真核表达载体的构建及其高表达对细胞凋亡的影响[J].中国药理学通报,2014,(11):1535.
 CHEN Zhong-lin,JIANG Hong-yan,HONG Xiao-bing,et al.Construction of Hi FGF2 eukaryotic expression plasmids and its over-expression induced cell apoptosis[J].Chinese Pharmacological Bulletin,2014,(10):1535.
[6]谢英花,马燕山,张 楠,等.硫化氢抑制离体灌流大鼠急性心肌缺血所致心肌细胞凋亡研究[J].中国药理学通报,2014,(11):1543.
 XIE Ying-hua,MA Yan-shan,ZHANG Nan,et al.Hydrogen sulfide inhibits cardiomyocyte apoptosis induced by acute myocardial ischemia in isolated perfused rat heart[J].Chinese Pharmacological Bulletin,2014,(10):1543.
[7]廖朝霞,王 飞,曹德雄,等.p38 MAPK信号通路在异氟醚诱导新生大鼠海马神经细胞凋亡的作用[J].中国药理学通报,2014,(12):1661.
 LIAO Zhao-xia,WANG Fei,CAO De-xiong,et al.Effect of p38 MAPK pathway on isoflurane-induced neuronal apoptosis in hippocampus of neonatal rats[J].Chinese Pharmacological Bulletin,2014,(10):1661.
[8]雷梅先,王云开,殷 然,等.肝X受体通过NF-κB信号通路减轻高糖诱导的H9C2细胞凋亡[J].中国药理学通报,2014,(12):1698.
 LEI Mei-xian,WANG Yun-kai,YIN Ran,et al.Liver X receptors attenuate high glucose-induced apoptosis in H9C2 cells through NF-κB signaling pathway[J].Chinese Pharmacological Bulletin,2014,(10):1698.
[9]林 岩,肖 薇,金 莉,等.内质网应激介导白藜芦醇对心肌细胞肥大的保护作用[J].中国药理学通报,2014,(12):1721.
 LIN Yan,XIAO Wei,JIN Li,et al.Protection action of resveratrol on cardiomyocyte hypertrophy mediated by endoplasmic reticulum stress[J].Chinese Pharmacological Bulletin,2014,(10):1721.
[10]李永金,杨开勇,张 谊,等.低氧诱导因子-1α在喹啉酸诱导的PC12细胞损伤中的作用[J].中国药理学通报,2015,(04):493.
 LI Yong-jin,YANG Kai-yong,ZHANG Yi,et al.Role of HIF-1α in quinolinic acid-induced injury in PC12 cells[J].Chinese Pharmacological Bulletin,2015,(10):493.


基金项目:国家自然科学基金资助项目(No 81674008); 湖南省科技厅资助项目(No 2013FJ4056)
作者简介:申 震(1989-),男,博士生,研究方向:中医药防治骨与关节损伤,E-mail:863491423@qq.com;
更新日期/Last Update: 2018-08-26