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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Homocysteine decreases blood flow to the brain due to vascular resistance in carotid artery.
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Homocysteine decreases blood flow to the brain due to vascular resistance in carotid artery.

机译：同型半胱氨酸由于颈动脉的血管阻力而减少了流向大脑的血液。

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摘要

An elevated level of Homocysteine (Hcy) is a risk factor for vascular dementia and stroke. Cysthathionine beta Synthase (CBS) gene is involved in the clearance of Hcy. Homozygous individuals for (CBS-/-) die early, but heterozygous for (CBS-/+) survive with high levels of Hcy. The gamma-Amino Butyric Acid (GABA) presents in the central nervous system (CNS) and functions as an inhibitory neurotransmitter. Hcy competes with GABA at the GABA(A) receptor and affects the CNS function. We hypothesize that Hcy causes a decrease in blood flow to the brain due to increase in vascular resistance (VR) because of arterial remodeling in the carotid artery (CA). Blood pressure and blood flow in CA of wild type (WT), CBS-/+, CBS-/+ GABA(A)-/- double knockout, and GABA(A)-/- were measured. CA was stained with trichrome, and the brain permeability was measured. Matrix Metalloproteinases (MMP-2 and MMP-9), tissue inhibitor of metalloproteinase (TIMP-3, TIMP-4), elastin, and collagen-III expression were measured by real-time polymerase chain reaction (RT-PCR). Results showed an increase in VR in CBS-/+/GABA(A)-/-double knockout>CBS-/+/>GABA(A)-/- compared to WT mice. Increased MMP-2, MMP-9, collagen-III and TIMP-3 mRNA levels were found in GABA(A)-/-, CBS-/+, CBS-/+/GABA(A) double knockout compared to WT. The levels of TIMP-4 and elastin were decreased, whereas the levels of MMP-2, MMP-9 and TIMP-3 increased, which indirectly reflected the arterial resistance. These results suggested that Hcy caused arterial remodeling in part, by increase in collagen/elastin ratio thereby increasing VR leading to the decrease in CA blood flow.
机译：同型半胱氨酸（Hcy）水平升高是血管性痴呆和中风的危险因素。胱硫醚β合酶（CBS）基因参与Hcy的清除。 （CBS-/-）的纯合子个体较早死亡，但（CBS-/ +）的杂合子以高水平的Hcy存活。 γ-氨基丁酸（GABA）存在于中枢神经系统（CNS）中，并起抑制性神经递质的作用。 Hcy在GABA（A）受体上与GABA竞争，并影响CNS功能。我们假设由于颈动脉（CA）中的动脉重构，Hcy导致由于血管阻力（VR）的增加而导致流向大脑的血流减少。测量了野生型（WT），CBS-/ +，CBS-/ + GABA（A）-/-双敲除和GABA（A）-/-中CA的血压和血流量。用三色染料对CA染色，并测量脑通透性。通过实时聚合酶链反应（RT-PCR）测量基质金属蛋白酶（MMP-2和MMP-9），金属蛋白酶组织抑制剂（TIMP-3，TIMP-4），弹性蛋白和胶原III的表达。结果显示，与野生型小鼠相比，CBS-/ + / GABA（A）-/-双重敲除> CBS-/ + GABA（A）-/-的VR升高。与WT相比，在GABA（A）-/-，CBS-/ +，CBS-/ + / GABA（A）双敲除中发现MMP-2，MMP-9，胶原蛋白III和TIMP-3 mRNA水平升高。 TIMP-4和弹性蛋白的水平降低，而MMP-2，MMP-9和TIMP-3的水平升高，这间接反映了动脉阻力。这些结果表明，Hcy通过胶原蛋白/弹性蛋白比的增加而部分引起动脉重塑，从而增加VR从而导致CA血流减少。

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