厄贝沙坦对脂质肾损害大鼠骨调素和单核细胞超趋化蛋白表达的影响

The effect of irbersartan on the osteopontin and MCP-1 expression in lipid-induced renal injury

目的 探讨高胆固醇血症模型大鼠的骨调素 (OPN)和单核细胞趋化蛋白 (MCP 1)与巨噬细胞的关系及厄贝沙坦的治疗作用。 方法 大鼠被随机分为 3组 :正常组 10只 ,高脂组 15只 ,高脂 +厄贝沙坦组 (治疗组 ) 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 (Ccr) ,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和MCP 1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 ,Ccr不受影响 ;(2 )高脂组大鼠肾OPN和MCP 1表达较对照组增加 (2 34± 0 2 5和 0 4 9± 0 11、1 93± 0 2 1和 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 37和 0 6 5± 0 2 4 ,P <0 0 5 ) ,主要位于小管间质区域 ,OPN和MCP 1均与ED1+ 细胞数呈高度正相关 (相关系数分别为 0 91和0 83,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和MCP 1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和MCP 1表达 。

Objective To investigate the expression of osteopontin(OPN) and monocyte chemoattractant protein-1(MCP-1) and the effect of Irbersartan on them in diet-hypercholesterolemia rats. Methods Wistar rats were divided into three groups: normal control rats(C), cholesterol fed rats(H) and cholesterol fed rats treated with Irbesartan(50 mg · kg -1 · d -1 ). Twelve weeks later, we measured the 24 hours total urine protein, creatinine clearance and total serum cholesterol, LDL- cholesterol, HDL- cholesterol and triglycerides. Kidney pathology was observed. Immunohistochemistry was used to analyse the expression of OPN, MCP-1, 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 that in C group rats, there was no significant difference between two groups in HDL-cholesterol and triglycerides.(2) Compared with C group rats , the expression of OPN and MCP-1 increased in cortical tubular epithelium (2.34±0.25 vs 0.49±0.11; 1.93±0.21 vs 0.49±0.11, P <0.05) and the number of ED1 + cell increased in tubulointerstitium of cholesterol fed rats, either OPN or MCP-1 expression was positively correlated with the number of ED1 + cell ( r =0.91 ,0.83 , P <0.05). (3) Irbesartan significantly inhibited the expression of OPN and MCP-1, and ameliorated macrophage infiltration. Conclusions The expression of OPN and MCP-1 in tubular epithelium increaseds and has a close relationship with macrophage infiltration into tubulointerstitium in hypercholesterolemia rats. Irbesartan has some protective effect partly through down-regulating OPN and MCP-1 expression and reducing macrophage infiltration.