[1]卢龙,贺伟峰,王益,等.干细胞因子联合抗白细胞介素17A抗体对小鼠脑缺血预后的影响[J].第三军医大学学报,2017,39(05 ):455-459.
 Lu Long,He Weifeng,Wang Yi,et al.Effect of stem cell factor combined with anti-interleukin 17A antibody on prognosis of cerebral ischemia in mice[J].J Third Mil Med Univ,2017,39(05 ):455-459.

干细胞因子联合抗白细胞介素17A抗体对小鼠脑缺血预后的影响(/HTML )




Effect of stem cell factor combined with anti-interleukin 17A antibody on prognosis of cerebral ischemia in mice
Lu Long He Weifeng Wang Yi Wen Shan Hu Jun Shi Shugui

Department of Neurology, 2State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Burns, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China

cerebral ischemia inflammation interleukin-17 stem cell factor

目的     探讨干细胞因子(stem cell factor,SCF)联合抗白细胞介素-17A抗体(anti-IL-17A)对小鼠脑缺血预后的影响。方法     通过线栓法对C57BL/6小鼠建立大脑中动脉栓塞(middle cerebral artery occlusion,MCAO)模型,60 min后取出线栓,恢复右侧大脑中动脉血流,建立脑缺血再灌注模型。小鼠脑缺血再灌注后分别给予腹腔注射生理盐水(normal saline,NS)、anti-IL-17A、SCF、anti-IL-17A+SCF。观察各组小鼠MCAO术后脑梗死体积、脑组织病理损伤和脑水肿程度、神经功能评分、神经细胞凋亡和炎症反应等变化。结果      与NS组相比,其余各治疗组脑梗死体积、脑组织病理损伤和脑水肿均显著减轻(P<0.05),神经功能评分得到明显改善(P<0.05),神经细胞凋亡减少(P<0.05),且anti-IL-17A+SCF组显著优于anti-IL-17A组和SCF组(P<0.05)。此外,anti-IL-17A还能明显减少脑组织IL-17A和IL-1β的表达(P<0.05)。结论      SCF联合anti-IL-17A能更好地改善脑缺血损伤和促进神经功能恢复。


Objective      To determine the effect of stem cell factor (SCF) combined with anti-interleukin 17A (anti-IL-17A) antibody on the prognosis of cerebral ischemia in mice. Methods      Mouse model of middle cerebral artery occlusion (MCAO) were induced in C57BL/6 mice by inserting nylon monofilament through the right common carotid artery for 60 min followed by reperfusion. Then the mice were respectively given normal saline (NS), anti-IL-17A, SCF, anti-IL-17A+SCF through intraperitoneal injection after cerebral ischemia and reperfusion. The changes of cerebral infarct volumes, pathological injury severity and brain edema, neurological deficits, apoptosis and inflammatory response of neural cells after MCAO were observed in each group. Results      Compared with the NS group, the cerebral infarct volume, pathological injury severity and brain edema were significantly alleviated in the other treatment groups (P<0.05). The neurological deficits were significantly improved (P<0.05), and the apoptosis of neurons was decreased in the treated groups (P<0.05). Furthermore, the effect of anti-IL-17A+SCF treatment was better than that of anti-IL-17A and SCF alone treatment (P<0.05). In addition, anti-IL-17A significantly reduced the expression levels of IL-17A and IL-1β in the brain tissues. Conclusion      SCF combined with anti-IL-17A can better improve the cerebral ischemia injury and promote the recovery of neurological function.


[1]Macrez R, Ali C, Toutirais O, etal. Stroke and the immune system: from pathophysiology to new therapeutic strategies[J]. Lancet Neurol, 2011, 10(5): 471-480. DOI:10.1016/S1474-4422(11)70066-7
[2]Fu Y, Liu Q, Anrather J, etal. Immune interventions in stroke[J]. Nat Rev Neurol, 2015, 11(9): 524-535. DOI:10.1038/nrneurol.2015.144
[3]Shichita T, Sugiyama Y, Ooboshi H, etal. Pivotal role of cerebral interleukin-17-producing gammadeltaT cells in the delayed phase of ischemic brain injury[J]. Nat Med, 2009, 15(8): 946-950. DOI:10.1038/nm.1999
[4]Gelderblom M, Weymar A, Bernreuther C, etal. Neutralization of the IL-17 axis diminishes neutrophil invasion and protects from ischemic stroke[J]. Blood, 2012, 120(18): 3793-3802. DOI:10.1182/blood2012-02-412726
[5]Zhao L R, Singhal S, Duan W M, etal. Brain repair by hematopoietic growth factors in a rat model of stroke[J]. Stroke, 2007, 38(9): 2584-2591. DOI:10.1161/STROKEAHA.106.476457
[6]Sugimori H, Yao H, Ooboshi H, etal. Krypton laserinduced photothrombotic distal middle cerebral artery occlusion without craniectomy in mice[J]. Brain Res Brain Res Protoc, 2004, 13(3): 189-196. DOI:10.1016/j.brainresprot.2004.06.001
[7]Longa E Z, Weinstein P R, Carlson S, etal. Reversible middle cerebral artery occlusion without craniectomy in rats[J]. Stroke, 1989, 20(1): 84-91. DOI:10.1161/01.str.20.1.84
[8]李惠允. 短暂性脑缺血发作患者的相关危险因素及引起脑梗死的风险预测[D]. 第三军医大学, 2015.
Li Huyun, The risk factors of transient ischemic attack patients and its risk of stroke[D]. Third Military Medical University, 2015
[9]Brea D, Agulla J, Rodríguez-Yá-ez M, etal. Regulatory T cells modulate inflammation and reduce infarct volume in experimental brain ischaemia[J]. J Cell Mol Med, 2014, 18(8): 1571-1579. DOI:10.1111/jcmm.12304
[10]Perez-de-Puig I, Miró-Mur F, Ferrer-Ferrer M, etal. Neutrophil recruitment to the brain in mouse and human ischemic stroke[J]. Acta Neuropathol, 2015, 129(2): 239-257. DOI:10.1007/s00401-014-1381-0
[11]Iwakura Y, Ishigame H, Saijo S, etal. Functional specialization of interleukin-17 family members[J]. Immunity, 2011, 34(2): 149-162. DOI:10.1016/j.immuni.2011.02.012
[12]Shichita T, Konoeda F, Yoshimura A. Role of T lymphocytes in ischemic brain injury[J]. Clinical neurology, 2010, 50(11): 878-880. DOI:10.5692/clinicalneurol.50.878
[13]Zhang J, Mao X, Zhou T, etal. IL-17A contributes to brain ischemia reperfusion injury through calpain-TRPC6 pathway in mice[J]. Neuroscience, 2014, 274: 419-428. DOI:10.1016/j.neuroscience.2014.06.001
[14]Doycheva D, Shih G, Chen H, etal. Granulocyte-colony Stimulating Factor in Combination with Stem Cell Factor Confers Greater Neuroprotection after HypoxicIschemic Brain Damage in the Neonatal Rats than a Solitary Treatment[J]. Translational Stroke Research, 2012, 4(2): 171-178. DOI:10.1007/s12975-012-0225-2
[15]Jin K, Mao X O, Sun Y, etal. Stem cell factor stimulates neurogenesis in vitro and in vivo[J]. J Clin Invest, 2002, 110(3): 311-319. DOI:10.1172/JCI15251


 Wang Kejing,Cheng Yu,Zhou Yuanda.Lindley eupatorium herb extract prevents and attenuates vascular inflammation reaction in atherosclerosis rabbits[J].J Third Mil Med Univ,2012,34(05 ):1853.
 HAO Li-yun,LI Xiao-hui.Alternation of blood pressure and behavioral performance in rat offspring following maternal inflammation during pregnancy[J].J Third Mil Med Univ,2008,30(05 ):897.
 CUI Song,HE Guo-xiang,CHENG Xun-min,et al.Correlation between intravascular ultrasound features of atherosclerotic plaques and high-sensitivity C-reactive protein[J].J Third Mil Med Univ,2007,29(05 ):167.
 LIU Xi,ZHOU Nai-kang,ZHANG Jin-ming,et al.Experimental study on biodistribution and PET imaging of 3’-deoxy-3’-18F-fluorothymidine in murine models of lung carcinoma and inflammation[J].J Third Mil Med Univ,2007,29(05 ):798.
 Liu Hong,Liu Qing,Lei Han,et al.Inflammatory stress promotes lipid accumulation in aorta of scavenger double knockout mice[J].J Third Mil Med Univ,2010,32(05 ):1728.
 Li Shengjun,Li Mengwen,Zhang Yan,et al.TAT-NBD exerts anti-inflammatory effect in rat cortical astrocytes by inhibiting bilirubin-induced nuclear factor-κB activation[J].J Third Mil Med Univ,2015,37(05 ):2131.

更新日期/Last Update: 2017-03-10