肢体缺血后处理对大鼠慢性脑缺血后脑内LINGO-1的表达及神经功能的变化
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摘要
目的:观察大鼠肢体缺血后处理后脑内LINGO-1表达的变化,研究肢体缺血后处理改善慢性脑缺血后神经损伤的分子机制。方法:采用50%三氯化铁处理双侧颈总动脉的方法建立慢性脑缺血模型,随机将大鼠分为假手术组、模型组和肢体缺血后处理组。大鼠肢体缺血后处理3周后采用三等分Y型电迷宫方法观察各组大鼠的学习记忆能力,RT-qPCR检测LINGO-1的mRNA,Western blot法测定LINGO-1的蛋白水平。结果:与模型组相比,肢体缺血后处理组大鼠学习记忆能力显著增加(P<0.05)。假手术组大鼠LINGO-1的mRNA及蛋白水平有少量阳性表达。肢体缺血后处理组大鼠LINGO-1的mRNA及蛋白水平均显著下降(P<0.05)。结论:慢性脑缺血大鼠脑内LINGO-1水平明显上调,肢体缺血后处理可明显降低LINGO-1的表达水平,并提高学习记忆能力,这可能是肢体缺血后处理改善慢性脑缺血神经功能的分子机制之一。
AIM: To observe the expression of LINGO-1 in the rat brain after ischemic stroke,and to explore the molecular mechanism of improving the neural damage after chronic cerebral ischemia by limb ischemic preconditioning(LIP). METHODS: The chronic cerebral ischemia model was established by the method of processing bilateral common carotid arteries with 50% FeCl3. The rats were randomly divided into sham operation group,model group and LIP group.The study and memory abilities of the animals were observed by the test of Y-type labyrinth after treatment for 2 weeks,and the mRNA and protein expression of LINGO-1 was detected by RT-q PCR and Western blot. RESULTS: Compared with model group,the study and memory abilities were significantly increased(P < 0. 05). Only a small amount of positive expression of LINGO-1 at mRNA and protein levels in sham operation group was observed. The expression of LINGO-1 in model group was increased significantly. Compared with model group,the expression of LINGO-1 at mRNA and protein levels was significantly decreased in LIP group(P < 0. 05). CONCLUSION: LIP improves the study and memory abilities and reduces the expression level of LINGO-1. LINGO-1 may be one of the molecular targets for LIP improving the neural function of chronic cerebral ischemia.
AIM: To observe the expression of LINGO-1 in the rat brain after ischemic stroke,and to explore the molecular mechanism of improving the neural damage after chronic cerebral ischemia by limb ischemic preconditioning(LIP). METHODS: The chronic cerebral ischemia model was established by the method of processing bilateral common carotid arteries with 50% FeCl3. The rats were randomly divided into sham operation group,model group and LIP group.The study and memory abilities of the animals were observed by the test of Y-type labyrinth after treatment for 2 weeks,and the mRNA and protein expression of LINGO-1 was detected by RT-q PCR and Western blot. RESULTS: Compared with model group,the study and memory abilities were significantly increased(P < 0. 05). Only a small amount of positive expression of LINGO-1 at mRNA and protein levels in sham operation group was observed. The expression of LINGO-1 in model group was increased significantly. Compared with model group,the expression of LINGO-1 at mRNA and protein levels was significantly decreased in LIP group(P < 0. 05). CONCLUSION: LIP improves the study and memory abilities and reduces the expression level of LINGO-1. LINGO-1 may be one of the molecular targets for LIP improving the neural function of chronic cerebral ischemia.
引文
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[2]Jang YH,Kim JH,Ban C,et al.Stromal cell derived factor-1(SDF-1)targeting reperfusion reduces myocardial infarction in isolated rat hearts[J].Cardiovasc Ther,2012,30(5):264-272.
[3]Yang XM,Liu Y,Cui L,et al.Platelet P2Y12 blockers confer direct postconditioning-like protection in reperfused rabbit hearts[J].Cardiovasc Pharmacol Ther,2013,18(3):251-262.
[4]李树清,李凡,何亮,等.缺血后适应促进树鼩血栓性脑缺血时紧密连接occludin/ZO-1蛋白表达及抑制脑水肿的机制[J].中国病理生理杂志,2016,32(3):477-484.
[5]Bai Y,Markham K,Chen F,et al.The in vivo brain interactome of the amyloid precursor protein[J].Mol Cell Proteomics,2008,7(1):15-34.
[6]Fernandez-Enright F,Andrews JL.LINGO-1:a novel target in therapy for Alzheimer’s disease?[J].Neural Regen Res,2016,11(1):88-89.
[7]Chen N,Cen JS,Wang J,et al.Neural stem cells promotes neuronal differentiation and functional recovery in rats subjected to spinal cord injury[J].Crit Care Med,2016,44(3):e146-e157.
[8]Zhang ZH,Li JJ,Wang QJ,et al.WNK1 is involved in Nogo66 inhibition of OPC differentiation[J].Mol Cell Neurosci,2015,65(1):135-142.
[9]Zhou ZD,Sathiyamoorthy S,Tan EK.LINGO-1 and neurodegeneration:pathophysiologic clues for essential tremor[J].Tremor Other Hyperkinet Mov(N Y),2012,2:tre-02-51-249-1.
[10]Ren C,Yan Z,Wei D,et al.Limb remote ischemic postconditioning protects against focal ischemia in rats[J].Brain Res,2009,1288:88-94.
[11]王诗才,陈太军,黄美松,等.脑源性神经营养因子保护H2O2诱导的氧化损伤血管内皮细胞[J].中国病理生理杂志,2015,31(8):1384-1394.
[12]Chen G,Yang J,Lu G,et al.Limb remote ischemic postconditioning reduces brain reperfusion injury by reversing e NOS uncoupling[J].Indian J Exp Biol,2014,52(6):597-605.
[13]Zhou Y,Fathali N,Lekic T,et al.Remote limb ischemic postconditioning protects against neonatal hypoxic-ischemic brain injury in rat pups by the opioid receptor/Akt pathway[J].Stroke,2011,42(2):439-444.