罗格列酮对阿霉素肾病大鼠足细胞nephrin表达的影响

Effect of rosiglitazone on podocyte's nephrin expression in adriamycin nephrotic rats

目的建立阿霉素肾病模型,探讨罗格列酮对阿霉素肾病大鼠足细胞nephrin的表达的影响。方法21只大鼠随机分为3组。阿霉素肾病组和罗格列酮组大鼠予0.1%阿霉素溶液7 mg·kg^(-1)一次性尾静脉注射,罗格列酮组次日予罗格列酮5 mg·kg^(-1)·d^(-1)灌胃,每日1次,共8 wk。另外2组每日予等量自来水灌胃。检测各组大鼠24 h尿蛋白定量、血清清蛋白、血脂、肾功能及肾脏病理改变,并检测肾组织nephrin和TCFβ_1的表达。结果给药后2、4、6、8 wk,罗格列酮组大鼠24 h尿蛋白定量明显低于阿霉素肾病组(P<0.05),8 wk时其血清清蛋白高于阿霉素肾病组[(26.7±s 2.6)g·L^(-1)vs(21±4)g·L^(-1),P<0.05],血三酰甘油和胆固醇水平低于阿霉素肾病组(P<0.05)。与阿霉素肾病组比较,罗格列酮组大鼠肾组织中nephrin蛋白表达增高19%(P<0.05),而TGFβ_1蛋白表达明显降低(P<0.01),肾脏病理损害也明显减轻。结论罗格列酮可上调阿霉素肾病大鼠肾组织nephrin表达,减少尿蛋白排泄,抑制其TGFβ_1表达,从而减轻肾组织病理损害。

AIM To investigate the effects of rosiglitazone on podocytes nephrin expression in established adriamycin nephrotic rat models. METHODS The rats were randomly assigned to three groups. The rats of adriamycin and rosiglitazone groups were induced by a single dose of 0.1% adriamycin （7 mg·kg^-1）injected into the tail vein,and then the rats of rosiglitazone group were treated furthermore with rosiglitazone （5 mg·kg^-1·d^-1） per day for eight consecutive weeks ,while the other rats received the same dose of normal saline for gastric infusion daily. Measurements of the levels of urinary protein,serum albumin,total blood cholesterol and triglyceride,renal function and pathologic changes were taken in rats after eight weeks together with the tests of the expressions of nephrin and TGFβ1 in kidney of the rats. RUSULTS Two,four,six,eight weeks after the rosiglitazone administration,24 h urinary protein compared to that of adriamycin group （P 〈 0.05）, excretion of rosiglitazone group decreased significantly as the serum albumin level increased as （26.7 ± s 2.6） g·L^-1 vs （21 ± 4）g·L^-1（P 〈 0.05） at 8 wk, but the serum total cholesterol and triglyceride decreased in the rats of rosiglitazone group （P 〈 0.01 ）. The pathological change in rats with adrimycine nephrosis were ameliorated by rosiglitazone presenting as the increase of nephrin protein expression （P 〈 0.05） and decrease of TGFβ1 protein expression in rosiglitazone group （P 〈 0.01 ）. CONCLUSION Rosiglitazone could up-regulate the expression of nephrin in rats with adrimycine nephrosis, and in turn decrease the urinary protein excretion, prohibit TGFβ1 expression; thus decrease the renal tissue pathologic damage.