创伤时阻断JAK/Stat3通路对大脑海马区神经组织细胞的影响
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摘要
目的探讨JAK/STAT通路对于创伤性脑缺血性的保护作用,为临床可能的基因治疗提供科学依据。方法45只wistar大鼠随机分为正常组(15只),创伤组(15只双下肢造成骨折)、干预组(15只,)创伤组和干预组分别在6h,48h,72h处死动物。取大鼠大脑海马区,一部分做常规病理切片,另一部分做qRT-PCR检测stat3mRNA,miR-21的基因表达。结果病理常规诊断:正常组,未见病理变化。创伤组,海马区神经细胞变性,染色不均,细胞变大,间质水肿。干预组,病理形态学变化较创伤组更加严重。qRT-PCR检测stat3,miR-21的表达显示,正常组,二者表达较低;创伤组,二者表达升高,在48h达到高峰,随后在72h下降。干预组二者表达均降低,在48h达到低谷,随后在72h逐渐的升高。二者呈正相关性(P<0.01)。结论创伤致脑组织缺氧时,stat3,miR-21表达升高起到了保护海马区神经细胞的作用,这一作用被AG490所阻断。
Objective Discussion JAK/stat3 protective effects of pathways on traumatic cerebral ischemia,provide scientific basis for clinical possible gene therapy.Methods 45 rats were randomly divided into normal group(15),trauma group(15,both lower extremities bone fracture)and intervention group.The trauma group and the intervention group were executed 6 h,48 hand 72 hrespectively.Hippocampal area,one part was routine pathology,the other was qRT-PCR detect stat3,miR-21 gene expression.Results pathologic diagnosis normal group no lesion;Compered with trauma group the nerve cells in the intervention group were damaged seriouely,which showed degeneralion,uneven staining enlargement,pyknosis,interstitial water and so on.Detection of stat3 and miR-21 expression by qRT-PCR:The expression of stat3 and miR-21 was lower in the nomal group;trauma group,the expression of both increased,reached the peak at 48 h,then decreased ay 72 h;intervention group,the trough at 48 h,and then 72 hpicked up,then is a positive correlation between the two.Conclusion in wound,the expression of stat3 and miR-21 increased,which played a protective role in the hippocampal neurons,which was blocked by AG490.
Objective Discussion JAK/stat3 protective effects of pathways on traumatic cerebral ischemia,provide scientific basis for clinical possible gene therapy.Methods 45 rats were randomly divided into normal group(15),trauma group(15,both lower extremities bone fracture)and intervention group.The trauma group and the intervention group were executed 6 h,48 hand 72 hrespectively.Hippocampal area,one part was routine pathology,the other was qRT-PCR detect stat3,miR-21 gene expression.Results pathologic diagnosis normal group no lesion;Compered with trauma group the nerve cells in the intervention group were damaged seriouely,which showed degeneralion,uneven staining enlargement,pyknosis,interstitial water and so on.Detection of stat3 and miR-21 expression by qRT-PCR:The expression of stat3 and miR-21 was lower in the nomal group;trauma group,the expression of both increased,reached the peak at 48 h,then decreased ay 72 h;intervention group,the trough at 48 h,and then 72 hpicked up,then is a positive correlation between the two.Conclusion in wound,the expression of stat3 and miR-21 increased,which played a protective role in the hippocampal neurons,which was blocked by AG490.
引文
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[20]Rozovski U,Calin GA,Setoyama T,et al.signal tranducer and actiwator of transcription(STAT3)regulates microRNA gene expression in chronic lymphocytic leukemia cells[J].Mol Cancer,2013,12(50):1476.
[21]Li Y,Wu R,Liu Z,et al.Enferced expression of microRNA-21influences the replication of varicellazostervirus by triggering signal transducer and activator of transcription3[J].Exp The Med,2014,2(5):1291.
[22]Li Y,Cai B,Xue XH,et al.TAT-mediated delivery of neuroglobin attenuates apoptosis induced by oxygen-glucose deprivation via the Jak2/stat3pothway in vitro[J].Neurol Res,2015,37(6):531.
[23]杨柳,陈蓓蕾,于洛龙,等.JAKsI/stat3信号通路与闹缺血再灌注损伤性关系研究进展[J].东南大学学报,2018,37(1):169.
[24]孔令平,刘爱华,周旋,等.stat3抑制剂WP1066增强顺铂对口腔鳞癌侵袭能力抑制作用的体外研究[J].天津医药,2016,44(1):38.
[2]Liu KD,Wilson JG,Zhuo H,et al.Design and implemen-tation of the START(STem cells for ARDS Treatment)trial,aphase 1/2trial of human mesenchymal stem/stromal cells for the treatment of moderate-severe acute re-spiratory distress syndrome[J].Ann Intensive Care,2014,4(1):22.
[3]Moidunny S,Matos M,Wesseling E,et al.Oncostatin M promotes excitotoxicity by inhibiting glutamate uptake in astrocytes:implications in HIV-associated neurotoxicity[J].J Neuroinflammation,2016,13(1):144.
[4]Luo Y,Yang Z,Su L,et al.Non-CSCs nourish CSCsthrough interleukin-17E-mediated activation of NF-κB and JAK/STAT3signaling in human hepatocellular car-cinoma[J].Cancer Lett,2016,375(2):390.
[5]Chen P,Huang L,Zhang YM,et al.The antagonist of the JAK-1/STAT-1signaling pathway improves the severity of ceruleinstimulated pancreatic injury via inhibition of NF-κB activity[J].Int J Mol Med,2011,27(5):731.
[6]Luo Y,Yang Z,Su L,et al.Non-CSCs nourish CSCsthrough interleukin-17E-mediated activation of NF-κB and JAK/STAT3signaling in human hepatocellular car-cinoma[J].Cancer Lett,2016,375(2):390.
[7]Nagata I,Uchino S,Tokuhira N,et al.Sepsis may not be a risk factor for mortality in patients with acute kidney injury treated with continuous renal replacement therapy[J].J Crit Care,2015,30(5):998.
[8]Wang X,Ma S,Liu Y,et al.Effects and mechanism anal-ysis of combined infusion by levosimendan and vasopres-sin on acute lung injury in rats septic shock[J].Cell Biochem Biophys,2014,70(3):1639.
[9]Janz DR,Ware LB.The role of red blood cells and cell-free hemoglobin in the pathogenesis of ARDS[J].J Intensive Care,2015,3(1):20.
[10]Liu KD,Wilson JG,Zhuo H,et al.Design and implemen-tation of the START(STem cells for ARDS Treatment)trial,aphase 1/2trial of human mesenchymal stem/stromal cells for the treatment of moderate-severe acute re-spiratory distress syndrome[J].Ann Intensive Care,2014,4(1):22.
[11]Mejias-Luque R,Peiro S,Vincent A,et al.IL-6induces MUC4expression through gp130/STAT3pathway in gas-tric cancer cell lines[J].Biochim Biophys Acta,2008,1783(10):1728.
[12]Wang X,Shaw S,Amiri F,et al.Inhibition of the Jak/STAT signaling pathway prevents the high glucose-in-duced increase in tgf-beta and fibronectin synthesis in mesangial cells[J].Diabetes,2002,51(12):3505.
[13]姚期,资红,孙宝飞.松树皮提取物对鼠脑缺血再灌注损伤的保护作用机制研究[J].中国实验动物学报,2017,25(6):632.
[14]Sun Y,Nadal-Vicens M,Misono S,et al.Neurogenin promotes neurogenesis and inhibits glial differentiation by independent mechanisms[J].Cell,2001,104(3):365.
[15]Benz F,Roy S,Trautwein C,et al.Circulating microRNAs as biomarker for sepsis[J].Internatingah Journal of Molecular Sciences,2016,17(1):78.
[16]Sehober A,Weber C.Mechenisms of microRNAs in atherosclerosis[J].Annu Rev Palhol,2016,11(3):586.
[17]万东,杨廷桐,秦玉凤,等.MicroRNA-21/PDCD4环路在卵巢癌中表达情况[J].肿瘤防治研究,2013,40(9):869.
[18]王玉,席乐峰,杨廷桐.C-myc与肺鳞癌中microRNA-21的表达关系[J].解剖学杂志,2013,36(4):758.
[19]陈惠军,杨廷桐.新生儿缺氧缺血性脑病血清中miR-21调控HIF-1a表达及临床意义[J].中国儿童保健杂志,2015,23(1):32.
[20]Rozovski U,Calin GA,Setoyama T,et al.signal tranducer and actiwator of transcription(STAT3)regulates microRNA gene expression in chronic lymphocytic leukemia cells[J].Mol Cancer,2013,12(50):1476.
[21]Li Y,Wu R,Liu Z,et al.Enferced expression of microRNA-21influences the replication of varicellazostervirus by triggering signal transducer and activator of transcription3[J].Exp The Med,2014,2(5):1291.
[22]Li Y,Cai B,Xue XH,et al.TAT-mediated delivery of neuroglobin attenuates apoptosis induced by oxygen-glucose deprivation via the Jak2/stat3pothway in vitro[J].Neurol Res,2015,37(6):531.
[23]杨柳,陈蓓蕾,于洛龙,等.JAKsI/stat3信号通路与闹缺血再灌注损伤性关系研究进展[J].东南大学学报,2018,37(1):169.
[24]孔令平,刘爱华,周旋,等.stat3抑制剂WP1066增强顺铂对口腔鳞癌侵袭能力抑制作用的体外研究[J].天津医药,2016,44(1):38.