厄贝沙坦对早期糖尿病肾脏疾病大鼠足细胞nephrin和podocin表达的影响

Effect of irbesartan on expression of nephrin and podocin in podocytes of rats with early diabetic ne- phropathy

目的：观察厄贝沙坦（irbesartan）对糖尿病肾脏疾病（diabetic kidney disease,DKD）大鼠足细胞裂孔隔膜蛋白分子（nephrin和 podocin）表达的影响,探讨厄贝沙坦对DKD的防治作用。方法以高脂高糖喂养8周联合小剂量链脲佐菌素（30 mg/kg）建立DKD大鼠模型,将 DKD大鼠模型随机分为2组：厄贝沙坦组及模型对照组；另设正常对照组。厄贝沙坦组给予厄旦沙坦（50 mg·kg-1·d-1）,另外2组每日给予等量0.9%生理盐水灌胃。各组于治疗前及药物干预后第4、8、12周周末检测大鼠血糖浓度和尿微量白蛋白量；观察大鼠体质量、肾重、肾肥大指数、血清尿素氮、肌酐、总胆固醇、三酰甘油变化；光镜观察肾脏病理改变；应用免疫组化技术观察足细胞相关蛋白 nephrin、podocin肾组织分布与表达；采用 Western blot技术测定肾皮质 nephrin、podocin 蛋白的表达。结果应用厄贝沙坦干预后与DKD对照组相比,大鼠的尿微量白蛋白总量、肾肥大指数、血糖、尿素氮、血肌酐较模型对照组明显降低（P〈0.05）,体质量增加（P〈0.05）,病理改变减轻,nephrin和 podocin蛋白表达增加（P〈0.05）。结论厄贝沙坦能上调 nephrin和 podocin的表达水平,降低尿微量白蛋白排泄,延缓DKD的进展。

Objective To observe the effects of irbesartan on the expression of nephrin and podocin in podocytes of rats with diabetic kidney disease （DKD）.Methods Rats were fed on high glucose and high fat diet in combination with a low dose of STZ to develop rat model of type 2 diabe-tes.The DKD rats were randomly divided into 2 groups：irbesartan treatment group and model group. In addition,the normal rats served as a normal control group.All rats were given daily gavage respec-tively for 8 weeks.The concentration of blood glucose and urinary microalbumin was monitored before and 4,8 and 12 weeks after treatment.Twelve weeks later,the body weight,kidney weight,KW/BW,blood urea nitrogen,serum creatinine,total cholesterol and triglyceride were detected by bio-chemical methods.The pathological changes of the kidney were also examined by a light microscope. The expression of nephrin and podocin in podocytes was detected by immunohistochemistry.The pro-tein levels of nephrin and podocin in the kidney tissue were also determined by Western blotting.Re-sults After irbesartan mixture intervention,the levels of urinary microalbumin,renal index,blood glucose concentration,BUN and SCr were significantly reduced,BW was increased,the pathological damage of the kidney were alleviated,and the expression of nephrin and podocin proteins was in-creased as compared with model group （P〈0.05 for all）.Conclusions Irbesartan could postpone the progression of DKD possibly by up-regulating the expression of nephrin and podocin,and decreasing the secretion of urinary microalbumin.