膳食碘在小鼠动脉粥样硬化发病中的保护作用
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国家自然科学基金项目(30700689)


The Effects of Dietary Iodine Intake on the Development of Atherosclerosis in Mice
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    摘要:

    目的研究碘摄入量对高脂血症小鼠甲状腺功能及血脂代谢的影响,探讨膳食中碘的摄入量在小鼠动脉粥样硬化发病中的保护作用及机制。方法选用4周龄的雌性c57BL/6小鼠,体重为16g左右。根据碘摄入量不同将小鼠随机分为重度低碘组、轻度低碘组、适碘组、10倍碘过量组和50倍碘过量组,每组10只。各组动物均用高脂高胆固醇低碘(碘含量为20~40μg/kg)饲料喂养。重度低碘组饮用去离子水,其他四组饮用含有不同浓度碘化钾(碘含量分别为196.08、326.79、3856.21和19542.5μg/L)的去离子水。各组小鼠饲养32周时处死。采用放射免疫法测定外周血甲状腺激素(TT4和TT3)水平;酶法测定外周血清中血脂水平;采用HE染色观察主动脉病理学改变;实时定量PCR检测小鼠主动脉组织细胞间黏附分子1、血管细胞黏附分子1和肝脏组织低密度脂蛋白受体的mRNA表达水平。结果(1)重度低碘组和轻度低碘组小鼠血清中TT4和TT3水平较适碘组均显著降低(P><0.05)。(2)重度低碘组小鼠血清中甘油三酯、总胆固醇和低密度脂蛋白胆固醇水平均较适碘组小鼠明显上升(P><0.01);轻度低碘组主要表现为低密度脂蛋白胆固醇水平明显高于适碘组(P><0.01);10倍碘过量组和50倍碘过量组小鼠血清中总胆固醇水平明显低于适碘组(P><0.01)。(3)病理学观察适碘组小鼠主动脉内膜内皮下间隙明显增宽,可见脂质沉积;轻度低碘组和重度低碘组小鼠主动脉内膜内皮下间隙较适碘组进一步增宽,部分区域可见散在泡沫细胞,其周围有少量脂质,可见指纹形成;10倍碘过量组和50倍碘过量组中只见主动脉内膜内皮下间隙稍有增宽,染色浅淡。(4)重度低碘组主动脉组织细胞间黏附分子1和血管细胞黏附分子1以及轻度低碘组的主动脉组织细胞间黏附分子1的mRNA表达水平均较适碘组显著升高(P><0.01),两组中肝脏组织低密度脂蛋白受体的mRNA表达水平均较适碘组明显降低(P><0.01);50倍碘过量组主动脉组织细胞间黏附分子1和血管细胞黏附分子1mRNA表达水平明显低于适碘组(P><0.05或P><0.01)。10倍碘过量组和50倍碘过量组中肝脏组织低密度脂蛋白受体mRNA表达水平均较适碘组升高(P><0.01)。结论膳食中的碘可通过影响小鼠甲状腺功能、血脂代谢及动脉组织黏附分子的表达,参与高脂高胆固醇喂养小鼠动脉粥样硬化的形成。低碘加重高脂血症小鼠动脉损伤,一定水平的碘可减轻高脂血症小鼠动脉损伤。

    Abstract:

    Aim To evaluate the effects of dietary iodine intake on the development of atherosclerosis in mice and to further investigate the association between iodine and cardiovascular disease.Methods Female C57BL/6 mice,weaning 1 month and weighing around 16 g,were randomly divided into five groups according to the iodine intakes:severe iodine deficiency(SID),mild iodine deficiency(MID),normal iodine(NI),10-fold high iodine(10 HI)and 50-fold high iodine(50 HI).All the mice were fed by high fat high cholesterol low iodine fodder(HFHCLI,iodine content is 20~40 μg/kg)and drank deionized water containing different concentrations of potassium iodide including 0 μg/L(SID),196.08 μg/L(MID),326.79 μg/L(NI),3 856.21 μg/L(10 HI)and 19 542.5 μg/L(50 HI)respectively.Eight months later,all the animals were sacrificed.Serum thyroid hormones(total T4 and total T3)were measured by radio immunoassay.The levels of triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDLC),low density lipoprotein cholesterol(LDLC)in the serum were detected enzymatically by automatic analysis.The extent of lesion development in the proximal aorta or aortic root was observed by hematoxylin-eosin staining on the paraffin-embeded tissue slides.Real-time PCR was applied to detect the expressions of intercellular adhesion molecule-1(ICAM-1)mRNA and vascular cell adhesion molecule-1(VCAM-1)mRNA in aorta and low-density lipoprotein receptor(LDLR)mRNA in liver.Results(1)The levels of thyroid hormones(total T4 and total T3)were distinctively decreased in SID and MID,especially in SID,compared with NI group(P><0.01 or P><0.05).(2)The levels of TG,TC and LDLC in SID and LDLC in MID were obviously higher than that in NI group(P><0.01).In contrast,the levels of TC in both 10 HI and 50 HI groups were statistically lower than NI group(P><0.01).(3)Pathological changes showed that in the tunica intima,sub-endothelial space was obviously wider with lipids deposition in NI.In MID and SID,sub-endothelial space was progressively wider and foam cells were found in regional area with some lipids around them,called fatty streak formation.In 10 HI and 50 HI group,sub-endothelial space was just slightly wider and the staining was pale.(4)Both ICAM-1 and VCAM-1 mRNA in the aorta tissues were highly expressed in SID than NI group(P><0.01).Similarly,the expression level of ICAM-1 mRNA in MID group was higher than NI group(P><0.01).In contrast,much lower expressions of these adhesion molecules were detected in 50 HI group compared with NI group(P><0.01 or P><0.05).The expression levels of LDLR mRNA in liver in SID and MID group were much lower while higher in 10 HI and 50 HI group than NI group(P><0.01 or P><0.05).Conclusion Dietary iodine intake could influence the development of atherosclerosis in mice fed by lipid-enriched diets by regulating thyroid function,the metabolism of serum lipids and the gene expression in liver.Iodine deficiency can have deleterious effects on the cardiovascular system,and a higher iodine intake may benefit it.

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赵树君,叶艳,孙富军,田恩江,陈祖培.膳食碘在小鼠动脉粥样硬化发病中的保护作用[J].中国动脉硬化杂志,2010,18(10):770~774.

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  • 收稿日期:2010-08-06
  • 最后修改日期:2010-10-09
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