血清同型半胱氨酸水平升高促进大鼠颅内动脉瘤的形成
Elevated serum homocysteine promotes the formation of intracranial aneurysms in rats
孙艳 1张巧莲 2刘莉 1王会荣 3黄生炫4
作者信息
- 1. 300162 天津,武警特色医学中心神经重症医学科
- 2. 300162 天津,武警特色医学中心神经内科
- 3. 721000 陕西,宝鸡市人民医院神经外科
- 4. 365000 福建三明,福建医科大学附属三明市第一医院神经外科
- 折叠
摘要
目的 探讨颅内动脉瘤大鼠模型的构建方法及高同型半胱氨酸血症对大鼠颅内动脉瘤形成的影响.方法 将36只SD雌性成年大鼠随机等分为3组,即传统模型组、新模型组和对照组,每组12只.传统模型组切除双侧卵巢,结扎双侧肾动脉后支和左侧颈总动脉,造模后1周喂以含8%氯化钠饲料;新模型组按同样方法造模后1周喂以含8%氯化钠和3%的L-甲硫氨酸的饲料;对照组仅暴露左侧颈总动脉和双肾,饲喂普通饲料.造模前及造模后1、6个月,测量血压1次;造模后6个月,检测血清雌二醇和同型半胱氨酸(Hcy),以及外周血基质金属蛋白酶-9(MMP-9)、诱导型一氧化氮合酶(iNOS)、单核细胞趋化蛋白-1(MCP-1)和超氧化物歧化酶(SOD)mRNA水平;扫描电镜观察颅内动脉瘤形成情况.结果 三组大鼠初始血压无统计学差异(P>0.05);造模1个月,传统模型组和新模型组大鼠血压均显著升高(P<0.05);造模后6个月,新模型组大鼠血压显著高于传统模型组(P<0.05).造模6个月,新模型组大鼠血清Hcy水平[(46.87±9.09)mol/L]明显高于传统模型组[(14.32±5.61)mol/L;P<0.05]和对照组[(15.29±4.90)mol/L;P<0.05].造模6个月,新模型组[(103.16±7.20)pmol/L]和传统模型组[(95.43±8.28)pmol/L]大鼠血清雌二醇水平明显低于对照组[(176.72±11.41)pmol/L;P<0.05].传统模型组和新模型组大鼠外周血MMP-9、iNOS、SOD mRNA水平较对照组均明显增高(P<0.05),而且新模型组明显高于传统模型组(P<0.05).新模型组颅内动脉瘤形成率(91.67%)明显高于传统模型组(41.67%;P<0.05).结论 L-甲硫氨酸喂养大鼠可诱导形成高同型半胱氨酸血症,血清同型半胱氨酸水平升高促进大鼠颅内动脉瘤的形成.
Abstract
Objective To investigate the method for establishing a rat model of intracranial aneurysm and the effect of hyperhomocysteinemia on the formation of intracranial aneurysms.Methods Thirty-six female adult SD rats were randomly divided into 3 groups:traditional model(TM)group,new model(NM)group and control group,with 12 rats in each group.Bilateral ovaries were removed,and the posterior branchs of the bilateral renal arteries and the left common carotid artery were ligated in the rats both in TM and NM groups.Then the rats in the TM group were fed with 8%sodium chloride diet for 1 week,and the rats in the NM group were fed with 8%sodium chloride diet with 3%L-methionine for 1 week.The left common carotid artery and both kidneys were exposed and normal diet was fed in rats in the control group.Blood pressures were measured before modeling,and 1 and 6 months after modeling.Serum estradiol and homocysteine(Hcy),and mRNA levels of matrix metalloproteinase-9(MMP-9),inducible nitric oxide synthase(iNOS),monocyte chemoattractant protein-1(MCP-1),and superoxide dismutase(SOD)in the peripheral blood were measured 6 months after modeling.The formation of intracranial aneurysm was observed by scanning electron microscope.Results There was no significant difference in the initial blood pressure among three groups(P>0.05).Blood pressures in the TM and NM groups were significantly increased 1 month after modeling(P<0.05).Blood pressure in the NM group was significantly higher than that in the TM group 6 months after modeling(P<0.05).Six months after modeling,the serum Hcy level in the NM group[(46.87±9.09)mol/L]was significantly higher than those in the TM group[(14.32±5.61)mol/L;P<0.05]and the control group[(15.29±4.90)mol/L;P<0.05].Six months after modeling,the serum estradiol levels in the NM group[(103.16±7.20)pmol/L]and the TM group[(95.43±8.28)pmol/L]were significantly lower than that[(176.72±11.41)pmol/L]in the control group(P<0.05).The mRNA levels of MMP-9,iNOS,and SOD in the TM and NM groups were siginificantly higher than that in the control group(P<0.05),and the mRNA levels of MMP-9,iNOS,and SOD in the NM group were significantly higher than those in the TM group(P<0.05).The intracranial aneurysm formation rate in the NM group(91.67%)was significantly higher than that(41.67%)in the TM group(P<0.05).Conclusions L-methionine feeding can induce hyperhomocysteinemia in adult SD rats,and the increase of serum homocysteine level promotes the formation of intracranial aneurysm in adult SD rats.
关键词
颅内动脉瘤/高同型半胱氨酸血症/动物模型/大鼠Key words
Intracranial aneurysm/Hyperhomocysteinemia/Animal model/Adult SD rats引用本文复制引用
基金项目
福建省卫生健康委科技项目(2021GGB022)
出版年
2024
NETL
NSTL
万方数据