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  

Effect of serum from patients with chronic renal insufficiency and indoxyl sulfate on lipid accumulation in macrophages in vitro

作　　者：申燕[1] 王沛[2] 周娟[3] 袁祖贻[2] 尹爱萍[1] 王丽君[3] 

机构地区：[1]西安交通大学医学院第一附属医院肾病中心肾内科,陕西西安710061 [2]西安交通大学医学院第一附属医院心内科,陕西西安710061 [3]西安交通大学环境与疾病相关基因教育部重点实验室,陕西西安710061

出　　处：《南方医科大学学报》2015年第5期631-638,共8页Journal of Southern Medical University

基　　金：国家自然科学基金(81200541);中央高校基本科研业务费专项资金(xjj2012065)~~

摘　　要：目的观察尿毒症apo E-/-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apo E-/-小鼠的动物模型,分别收集尿毒症apo E-/-小鼠、假手术apo E-/-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 m RNA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apo E-/-小鼠主动脉根部动脉粥样硬化斑块面积较假手术apo E-/-小鼠明显增大。5%的慢性肾功能不全患者血清及250μmol/L的硫酸吲哚酚可明显诱导巨噬细胞CD36 m RNA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 m RNA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。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.

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 

分 类 号：R692.5[医药卫生—泌尿科学]