毛诗贤,楚兰,陈红群
MAO Shixian,CHU Lan,CHEN Hongqun (Department of Neurology

• 1:贵阳医学院附院神经科

摘要(Abstract)：

目的:探讨阻断泛素蛋白酶体途径(ubiquitin proteasome pathway,UPP)对糖尿病大鼠局灶性脑缺血再灌注损伤的神经保护作用。方法:将Sprague-Dawley大鼠随机分成正常对照组(A组)、假手术组(B组)、非糖尿病组(C组)、糖尿病组(D组)、糖尿病治疗组(E组)及糖尿病治疗对照组(F组),链脲佐菌素腹腔注射制作糖尿病模型,线栓法制作大鼠大脑中动脉缺血2h再灌注模型;用clasto-lactacystin β-lactone阻断UPP,免疫组织化学方法观察再灌注24h后NF-κBp65的表达。结果:脑缺血再灌注24h后,NF-κBp65表达在D组较C组增加,在E组较D组和F组减少(P<0.05)。结论:糖尿病局灶性脑缺血NF-κBp65表达增多,阻断UPP可通过抑制NF-κBp65的活化而产生神经保护作用。
Objective:To study the mechanism of blocking ubiquition proteasome pathway (UPP) in protection of brain from ischemia reperfusion caused injury in diabetic rats. Methods:Sprague-Dawley (SD) rats were randomly divided into control group (group A),sham operation group (group B),non-diabetes cerebral infarction group (group C),diabetes cerebral infarction group (group D),diabetes cerebral infarction treatment group (group E) and diabetes cerebral infarction treatment control group (group F). Diabetic model was made by injection of streptozotocin through abdomen. Transient focal cerebral ischemia reperfusion was produced by middle cerebral artery occlusion for 2 hours in SD rats. The UPP was blocked by clasto-lactacystin β-lactone. The expression of NF-κBp65 was detected by immunohistochemistry method in 24 h after reperfusion. Results:In 24 h after the reperfusion,expression of NF-κBp65 in group D was higher than in group C,and was lower in group E than in groups D and F (P<0.05). Conclusion:Expression of NF-κBp65 increases in diabetic cerebral ischemia reperfusion rats,and the blocking UPP may perform neuroprotection effect by inhibiting the activation of NF-κBp65.

关键词(KeyWords)： 糖尿病;脑梗塞;再灌注损伤;大鼠,sprague-dawley
diabetes mellitus; brain infarction; reperfusion injury; rats,sprague-dawley

Abstract:

Keywords:

基金项目(Foundation):

作者(Author): 毛诗贤,楚兰,陈红群
MAO Shixian,CHU Lan,CHEN Hongqun (Department of Neurology

DOI: 10.19367/j.cnki.1000-2707.2010.03.010

参考文献(References)：

• [1]Amir RE,Iwai K,Ciechanover A.The NEDD8pathway is essential for SCF(beta-TrCP)-mediated ubiquitination and processing of the NF-kappa B precursor p105[J].J Biol Chem,2002(26):23253-23259.
• [2]Wojcik C,Di Napoli M.Ubiquitin-proteasome system and proteasome inhibition:newstrategies in stroke therapy[J].Stroke,2004(6):1506-1518.
• [3]刘磊,朱梅佳.实验性慢性糖尿病大鼠局灶性脑缺血再灌注模型的制作[J].中国现代神经疾病杂志,2005(1):45-50.
• [4]Nagasawa H,Kogure K.Correlation between cerebral blood flow and histologic changes in a new rat model of middle cerebral artery occlusion[J].Stroke,1989(8):1037-1043.
• [5]Pickart CM,Eddins MJ.Ubiquitin:structures,functions,mechanisms[J].Biochim Biophys Acta,2004(1-3):55-72.
• [6]Wang YH,Wang WY,Chang CC,et al.Taxifolin amel-iorates cerebral ischemia-reperfusion injury in rats through its anti-oxidative effect and modulation of NF-kappa B ac-tivation[J].J Biomed Sci,2006(1):127-141.
• [7]Song YS,Lee YS,Chan PH.Oxidative stress transiently decreases the IKK complex(IKKalpha,beta,and gam-ma),an upstream component of NF-kappaB signaling,af-ter transient focal cerebral ischemia in mice[J].J Cereb Blood Flow Metab,2005(10):1301-1311.
• [8]毛诗贤,杨期东,李振国等。阻断泛素-蛋白酶体途径在大鼠脑缺血再灌注损伤中的抗炎作用[J].国际神经病学神经外科学杂志,2005(4):298-300.
• [9]Pai S,Thomas R.Immune deficiency or hyperactivity-Nf-kaooab illuminates autoimmunity[J].J Autoimmun,2008(3):245-251.
• [10]杨军,胡新华,刘程伟,等.抑制核因子-κB减轻腹主动脉瘤破裂所致多脏器损伤的实验研究[J].中华医学杂志,2006(4):237-241.

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