脂质肾损害中骨调素的表达及其与巨噬细胞的关系

目的 :探讨高胆固醇血症大鼠模型中骨调素 (osteopontin ,OPN)的表达和巨噬细胞 (macrophage ,MΦ)浸润的关系及厄贝沙坦的治疗作用。方法 :动物被随机分为 3组 :正常组 (10只 ) ,高脂组 (15只 ) ,高脂 +厄贝沙坦组(15只 )。高脂组饲以高脂鼠料 ,厄贝沙坦组除高脂鼠料外 ,同时给予 5 0mg·kg-1·d-1厄贝沙坦灌胃 ,12周后检测各组血脂质、2 4h尿蛋白、内生肌酐清除率 ,HE及PAS染色观察肾脏病理改变 ,免疫组化方法检测肾组织中OPN的表达及单核细胞抗原阳性 (ED1+ )细胞数。结果 :①高脂组大鼠血脂增高 ,2 4h尿蛋白增高 ,内生肌酐清除率不受影响。②高脂组大鼠肾OPN表达增加 (2 .34± 0 .2 5vs 0 .4 9± 0 .11,P <0 .0 5 )主要位于皮质肾小管上皮细胞 ;ED1+ 细胞数增多 (6 .0 8± 1.37vs 0 .6 5± 0 .2 4 ,P <0 .0 5 ) ,主要位于小管间质区域 ,OPN与ED1+ 细胞数呈高度正相关 (r =0 .91,P <0 .0 5 )。③与高脂组相比 ,厄贝沙坦组血脂无变化 ,但 2 4h尿蛋白减少 ,肾组织表达OPN减少 ,ED1+ 细胞数减少 ,病理改变减轻。结论 :厄贝沙坦可通过下调高脂血症大鼠OPN表达 ,减少肾组织中MΦ浸润 ,发挥其肾保护作用。

Expression of Osteopontin and It's Relationship with Marophage Infusion in Lipid-Induced Renal Injury

Objective: To investigate the expression of osteopontin (OPN) and it’s relationship with macrophage(MΦ) infusion and the effect of Irbersartan on them in diet-hypercholesterolemia rats. Methods: Wistar rats were divided into three groups: normal control rats(C group), hyper-cholesterol fed rats(H group) and hyper-cholesterol fed rats treated with 50 mg·kg -1·d -1 Irbesartan(HI group). Twelve weeks later, the 24 hours total urine protein, creatinine clearance and total serum cholesterol, LDL- cholesterol, HDL- cholesterol and triglycerides were measured. Kidney pathology were observed. Immunohistochemistry were used to analyse the expression of OPN, ED1 +and their relationship. Results: ① Total serum cholesterol, LDL-cholesterol level and 24 h total urine protein in H group rats were higher than those in C group rats, and there were no significant difference between H group and HI group. ② Compared to C group rats , the expression of OPN increased in cortical tubular epithelium (2.34±0.25 vs 0.49±0.11, P< 0.05) and the number of ED1 + cell increased in tubulointerstitium of H group rats, and OPN expression was positively correlated with the number of ED1 + cell (r=0.91,P<0.05). ③ Irbesartan significantly inhibited the expression of OPN and ameliorated macrophage infiltration. Conclusion: The expression of OPN in tubular epithelium increases and has a close relationship with MΦ infiltration into tubulointerstitium in hypercholesterolemia rats. Irbesartan has some protective effects partly through down-regulating OPN expression and reducing MΦ infiltration.