發(fā)布時(shí)間：2019-02-16 12:44

【摘要】：目的:探討葉酸聯(lián)合維生素B12對(duì)高同型半胱氨酸血癥引起大鼠動(dòng)脈粥樣硬化的治療作用,并闡明其治療機(jī)制。方法:將33只大鼠隨機(jī)分為對(duì)照組、模型組和治療組,每組11只,對(duì)照組大鼠給予普通飼料,模型組大鼠給予普通飼料和蛋氨酸,治療組大鼠給予普通飼料和蛋氨酸同時(shí)灌胃給予葉酸和維生素B12。HE染色觀(guān)察大鼠胸主動(dòng)脈的病理組織形態(tài)表現(xiàn),ELISA法檢測(cè)大鼠血清同型半脫氨酸(Hcy)和基質(zhì)金屬蛋白酶9(MMP-9)水平,免疫組織化學(xué)染色檢測(cè)大鼠胸主動(dòng)脈平滑肌細(xì)胞中CC趨化因子受體5(CCR5)和CC趨化因子配體5(CCL5)蛋白表達(dá)水平,RT-PCR法檢測(cè)胸主動(dòng)脈平滑肌細(xì)胞中CCR5和CCL5mRNA表達(dá)水平。結(jié)果:HE染色,對(duì)照組大鼠胸主動(dòng)脈中膜平滑肌細(xì)胞排列整齊,內(nèi)彈力膜完整,內(nèi)皮細(xì)胞連續(xù);模型組大鼠胸主動(dòng)脈中膜平滑肌細(xì)胞紊亂疏松,內(nèi)膜損傷,內(nèi)膜下有泡沫細(xì)胞形成,內(nèi)皮細(xì)胞壞死脫落;治療組大鼠胸主動(dòng)脈病理組織形態(tài)表現(xiàn)介于對(duì)照組和模型組之間。模型組和治療組大鼠血清Hcy水平高于對(duì)照組(P0.05),治療組大鼠血清Hcy水平低于模型組(P0.05);模型組和治療組大鼠血清MMP-9水平高于對(duì)照組(P0.05),治療組大鼠血清MMP-9水平低于模型組(P0.05);模型組和治療組大鼠胸主動(dòng)脈平滑肌細(xì)胞中CCR5和CCL5蛋白灰度值低于對(duì)照組(P0.05),治療組大鼠胸主動(dòng)脈平滑肌細(xì)胞中CCR5和CCL5蛋白表達(dá)水平高于模型組(P0.05);模型組和治療組大鼠胸主動(dòng)脈平滑肌細(xì)胞中CCR5和CCL5mRNA相對(duì)表達(dá)水平高于對(duì)照組(P0.05),治療組大鼠胸主動(dòng)脈平滑肌細(xì)胞中CCR5和CCL5 mRNA相對(duì)表達(dá)水平低于模型組(P0.05)。結(jié)論:葉酸聯(lián)合維生素B12治療可以降低血清Hcy和MMP-9水平和胸主動(dòng)脈平滑肌細(xì)胞中CCR5及CCL5表達(dá)水平,這可能是葉酸聯(lián)合維生素B12治療動(dòng)脈粥樣硬化機(jī)制之一。
[Abstract]:Aim: to investigate the therapeutic effect of folic acid combined with vitamin B12 on atherosclerosis induced by hyperhomocysteinemia in rats and to elucidate its therapeutic mechanism. Methods: Thirty-three rats were randomly divided into control group (n = 11), model group (n = 11) and treatment group (n = 11). In the treatment group, rats were given common diet and methionine simultaneously by folic acid and vitamin B1 2.HE staining to observe the histopathological features of thoracic aorta in rats. The levels of homotypic (Hcy) and matrix metalloproteinase 9 (MMP-9) in serum of rats were detected by ELISA. The expressions of CC chemokine receptor 5 (CCR5) and CC chemokine ligand 5 (CCL5) in rat thoracic aortic smooth muscle cells were detected by immunohistochemical staining, and the expression of CCR5 and CCL5mRNA in thoracic aortic smooth muscle cells were detected by RT-PCR method. Results: HE staining showed that the medial smooth muscle cells of thoracic aorta of the control group were arranged neatly, the inner elastic membrane was intact, and the endothelial cells were continuous. In the model group, the medial smooth muscle cells of the thoracic aorta were in disorder and loose, the intima was damaged, foam cells were formed under the intima, endothelial cells were necrotic and exfoliated, and the histopathological features of the thoracic aorta in the treatment group were between the control group and the model group. The serum Hcy level in the model group and the treatment group was higher than that in the control group (P0.05), and the serum Hcy level in the treatment group was lower than that in the model group (P0.05). The serum MMP-9 level in the model group and the treatment group was higher than that in the control group (P0.05), and the serum MMP-9 level in the treatment group was lower than that in the model group (P0.05). The gray level of CCR5 and CCL5 protein in the model group and the treatment group was lower than that in the control group (P0.05). The expression of CCR5 and CCL5 protein in the aortic smooth muscle cells of the treatment group was higher than that in the model group (P0.05). The relative expression level of CCR5 and CCL5mRNA in the model group and the treatment group was higher than that in the control group (P0.05), and the relative expression level of CCR5 and CCL5 mRNA in the treatment group was lower than that in the model group (P0.05). Conclusion: folic acid combined with vitamin B12 can reduce the levels of serum Hcy and MMP-9 and the expression of CCR5 and CCL5 in thoracic aortic smooth muscle cells, which may be one of the mechanisms of folic acid combined with vitamin B12 in the treatment of atherosclerosis.
【作者單位】： 蘭州大學(xué)第一醫(yī)院神經(jīng)外科;蘭州大學(xué)第一醫(yī)院小兒科;
【基金】：甘肅省衛(wèi)計(jì)委衛(wèi)生行業(yè)計(jì)劃項(xiàng)目資助課題(GSWSKY-2015-43)
【分類(lèi)號(hào)】：R54

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