人尿激肽原酶抑制实验性脑卒中的脑炎症反应并下调核因子-κB。
Human urinary kallidinogenase suppresses cerebral inflammation in experimental stroke and downregulates nuclear factor-kappaB.
机构信息
Department of Neurology, Affiliated Drum Tower Hospital, Nanjing University Medical School, 321 Zhongshan Road, Nanjing, PR China.
出版信息
J Cereb Blood Flow Metab. 2010 Jul;30(7):1356-65. doi: 10.1038/jcbfm.2010.19. Epub 2010 Feb 24.
Abstract
The purpose of this study is to investigate the possible mechanism and the neuroprotective effect of human urinary kallidinogenase (HUK) in cerebral ischemia. The mouse middle cerebral artery occlusion (MCAO) model was used. Mice were treated with HUK (20 PNAU/g per day, intravenous) or saline as control, from the beginning of reperfusion to 72 h. Neurological deficits, infarct size, and BWC were measured at 6, 24, 48, and 72 h after MCAO, respectively. Pathological changes of brain were observed by TUNEL assay. Inflammatory factors were measured by real-time PCR and western blotting. Activation of MAPKs, Akt, and nuclear factor-kappaB (NF-kappaB) was detected by western blotting. Our results indicated that HUK significantly improved neurofunction, decreased infarct size, and suppressed edema, as well as inflammatory mediators as compared with the vehicle group. Furthermore, HUK inhibited the NF-kappaB pathway and activated the MAPK/ERK pathway in this neuroprotection.
摘要
本研究旨在探讨人尿激肽原酶（HUK）在脑缺血中的可能作用机制和神经保护作用。采用小鼠大脑中动脉闭塞（MCAO）模型。小鼠从再灌注开始至 72 h 每天接受 HUK（20 PNAU/g，静脉注射）或生理盐水治疗作为对照。分别于 MCAO 后 6、24、48 和 72 h 测量神经功能缺损、梗死面积和脑水含量。TUNEL 法观察脑病理变化。实时 PCR 和 Western blot 法测定炎性因子。Western blot 法检测 MAPKs、Akt 和核因子-κB（NF-κB）的激活。结果表明，与载体组相比，HUK 显著改善了神经功能，减少了梗死面积和脑水肿，抑制了炎症介质。此外，HUK 在这种神经保护作用中抑制了 NF-κB 途径并激活了 MAPK/ERK 途径。
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本文引用的文献
1
Inflammatory cytokines stimulate the chemokines CCL2/MCP-1 and CCL7/MCP-3 through NFkB and MAPK dependent pathways in rat astrocytes [corrected].
Brain Res. 2009 Sep 1;1287:47-57. doi: 10.1016/j.brainres.2009.06.081. Epub 2009 Jul 3.
2
Edema formation in the hyperacute phase of ischemic stroke. Laboratory investigation.
J Neurosurg. 2009 Nov;111(5):1036-42. doi: 10.3171/2009.3.JNS081040.
3
Icariin enhances neuronal survival after oxygen and glucose deprivation by increasing SIRT1.
Eur J Pharmacol. 2009 May 1;609(1-3):40-4. doi: 10.1016/j.ejphar.2009.03.033. Epub 2009 Mar 20.
4
Neuroprotection of interleukin-6 against NMDA attack and its signal transduction by JAK and MAPK.
Neurosci Lett. 2009 Jan 30;450(2):122-6. doi: 10.1016/j.neulet.2008.11.051. Epub 2008 Nov 27.
5
Tissue kallikrein elicits cardioprotection by direct kinin b2 receptor activation independent of kinin formation.
Hypertension. 2008 Oct;52(4):715-20. doi: 10.1161/HYPERTENSIONAHA.108.114587. Epub 2008 Sep 2.
6
Exogenous kallikrein enhances neurogenesis and angiogenesis in the subventricular zone and the peri-infarction region and improves neurological function after focal cortical infarction in hypertensive rats.
Brain Res. 2008 Apr 24;1206:89-97. doi: 10.1016/j.brainres.2008.01.099. Epub 2008 Mar 19.
7
Inflammation and ischaemic stroke.
Curr Opin Neurol. 2007 Jun;20(3):334-42. doi: 10.1097/WCO.0b013e32813ba151.
8
Brain oedema in focal ischaemia: molecular pathophysiology and theoretical implications.
Lancet Neurol. 2007 Mar;6(3):258-68. doi: 10.1016/S1474-4422(07)70055-8.
9
The inflammatory response in stroke.
J Neuroimmunol. 2007 Mar;184(1-2):53-68. doi: 10.1016/j.jneuroim.2006.11.014. Epub 2006 Dec 26.
10
Role of cocaine- and amphetamine-regulated transcript in estradiol-mediated neuroprotection.
Proc Natl Acad Sci U S A. 2006 Sep 26;103(39):14489-94. doi: 10.1073/pnas.0602932103. Epub 2006 Sep 13.
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