[1]申燕,王沛,周娟,等.慢性肾功能不全患者血清及硫酸吲哚酚对巨噬细胞脂质聚集的影响[J].南方医科大学学报,2015,(05):631.
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慢性肾功能不全患者血清及硫酸吲哚酚对巨噬细胞脂质聚集的影响()
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《南方医科大学学报》[ISSN:1673-4254/CN:44-1627/R]

卷:
期数:
2015年05期
页码:
631
栏目:
出版日期:
2015-05-15

文章信息/Info

Title:
Effect of serum from patients with chronic renal insufficiency and indoxyl sulfate on
lipid accumulation in macrophages in vitro
作者:
申燕王沛周娟袁祖贻尹爱萍王丽君
关键词:
慢性肾功能不全动脉粥样硬化硫酸吲哚酚巨噬细胞CD36泡沫细胞
Keywords:
chronic renal insufficiency atherosclerosis indoxyl sulfate macrophages CD36 foam cells
摘要:
目的观察尿毒症apoE-/-小鼠主动脉根部动脉粥样硬化病变,慢性肾功能不全患者血清和尿毒症毒素硫酸吲哚酚对巨噬
细胞胆固醇转运受体的表达及胞内脂质聚集的影响。方法外科手术法建立尿毒症apoE-/-小鼠的动物模型,分别收集尿毒症
apoE-/-小鼠、假手术apoE-/-小鼠、C57BL/6J小鼠的主动脉根部,行冰冻切片油红O染色,计算动脉粥样硬化斑块相对面积。收
集慢性肾功能不全患者及肾功正常者血清,以不同浓度的慢性肾功能不全患者血清或不同浓度的硫酸吲哚酚干预巨噬细胞株
12 h,测定不同干预条件下胆固醇转运受体SR-A1、CD36、ABCA1、ABCG1、SR-B1 mRNA的表达;干预24 h后诱导泡沫细胞,
油红O染色测定不同干预条件下细胞内脂质含量。结果尿毒症apoE-/-小鼠主动脉根部动脉粥样硬化斑块面积较假手术
apoE-/-小鼠明显增大。5%的慢性肾功能不全患者血清及250 μmol/L的硫酸吲哚酚可明显诱导巨噬细胞CD36 mRNA的表达
而不影响其余胆固醇转运受体的表达,同时增加巨噬细胞内脂质的蓄积。结论慢性肾功能不全加速动脉粥样硬化的进展,机
制与慢性肾功能不全血清中蛋白结合性尿毒症毒素硫酸吲哚酚诱导巨噬细胞CD36 mRNA表达上调、促进细胞内的脂质蓄积
有助于巨噬细胞源性泡沫细胞形成有关。
Abstract:
Objective To investigate the pathologies of aortic root atherosclerotic lesion in uremic apoE-/- mice and explore the
effect of serum from patients with chronic renal insufficiency (CRI) and the uremic toxin, indoxyl sulfate (IS), on the
expression of cholesterol transporting receptors and lipid accumulation in macrophages in vitro. Methods The uremic apoE-/-
mouse model was established by surgical operation. Frozen sections of the aortic root were collected from uremic apoE-/- mice,
sham-operated apoE-/- mice and C57BL/6J mice and stained with oil red O to calculate the relative area of atherosclerotic
plaque. Murine macrophage RAW264.7 cell line was treated for 12 h with different concentrations of IS or serum samples from
CRI patients and healthy individuals, and the mRNA expressions of cholesterol transporting receptors (SR-A1, CD36, ABCA1,
ABCG1 and SR-B1) were detected. After treatment for 24 h, the cells were induced into foam cells to determine lipid contents
using oil red O staining. Results The relative area of the atherosclerotic plaques in the aortic root increased significantly in
uremic apoE-/- mice compared with that in sham-operated apoE-/- mice. CRI serum (5%) and IS (250 μmol/L) obviously
increased the mRNA expression of CD36 and lipid accumulation in the macrophages, but did not affect the mRNA expression
of other cholesterol transporting receptors. Conclusion CRI can accelerate the progression of atherosclerosis through the
mechanism that IS in CRI serum promotes lipid accumulation in macrophages by enhancing the mRNA expression of CD36,
which contributes to the formation of foam cells.

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更新日期/Last Update: 1900-01-01