叶酸联合维生素B12对高同型半胱氨酸血症引起大鼠动脉粥样硬化的治疗作用

发布时间：2019-02-16 12:44

【摘要】：目的:探讨叶酸联合维生素B12对高同型半胱氨酸血症引起大鼠动脉粥样硬化的治疗作用,并阐明其治疗机制。方法:将33只大鼠随机分为对照组、模型组和治疗组,每组11只,对照组大鼠给予普通饲料,模型组大鼠给予普通饲料和蛋氨酸,治疗组大鼠给予普通饲料和蛋氨酸同时灌胃给予叶酸和维生素B12。HE染色观察大鼠胸主动脉的病理组织形态表现,ELISA法检测大鼠血清同型半脱氨酸(Hcy)和基质金属蛋白酶9(MMP-9)水平,免疫组织化学染色检测大鼠胸主动脉平滑肌细胞中CC趋化因子受体5(CCR5)和CC趋化因子配体5(CCL5)蛋白表达水平,RT-PCR法检测胸主动脉平滑肌细胞中CCR5和CCL5mRNA表达水平。结果:HE染色,对照组大鼠胸主动脉中膜平滑肌细胞排列整齐,内弹力膜完整,内皮细胞连续;模型组大鼠胸主动脉中膜平滑肌细胞紊乱疏松,内膜损伤,内膜下有泡沫细胞形成,内皮细胞坏死脱落;治疗组大鼠胸主动脉病理组织形态表现介于对照组和模型组之间。模型组和治疗组大鼠血清Hcy水平高于对照组(P0.05),治疗组大鼠血清Hcy水平低于模型组(P0.05);模型组和治疗组大鼠血清MMP-9水平高于对照组(P0.05),治疗组大鼠血清MMP-9水平低于模型组(P0.05);模型组和治疗组大鼠胸主动脉平滑肌细胞中CCR5和CCL5蛋白灰度值低于对照组(P0.05),治疗组大鼠胸主动脉平滑肌细胞中CCR5和CCL5蛋白表达水平高于模型组(P0.05);模型组和治疗组大鼠胸主动脉平滑肌细胞中CCR5和CCL5mRNA相对表达水平高于对照组(P0.05),治疗组大鼠胸主动脉平滑肌细胞中CCR5和CCL5 mRNA相对表达水平低于模型组(P0.05)。结论:叶酸联合维生素B12治疗可以降低血清Hcy和MMP-9水平和胸主动脉平滑肌细胞中CCR5及CCL5表达水平,这可能是叶酸联合维生素B12治疗动脉粥样硬化机制之一。
[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.
【作者单位】：兰州大学第一医院神经外科;兰州大学第一医院小儿科;
【基金】：甘肃省卫计委卫生行业计划项目资助课题(GSWSKY-2015-43)
【分类号】：R54

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