Elevated serum homocysteine promotes the formation of intracranial aneurysms in rats

SUN Yan; ZHANG Qiao-lian; LIU Li; WANG Hui-rong; HUANG Sheng-xuan

doi:10.13798/j.issn.1009-153X.2024.02.009

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.