厄贝沙坦治疗糖尿病肾病大鼠蛋白尿作用机制

Mechanism of action of irbesartan in treating proteinuria in diabetic nephropathy rats

目的研究厄贝沙坦治疗糖尿病肾病（DN）蛋白尿作用机制。方法应用链脲佐菌素建立大鼠糖尿病肾病模型，成模大鼠随机分为模型对照组（M）、厄贝沙坦干预组（I），另设正常对照组（C）。各组干预12周后，分别检测：①血糖、血肌酐、24h尿蛋白定量等；②肾脏病理、电镜以及免疫组化分析；③实时定量RT—PCR分析。结果与正常组比较，模型组大鼠24h尿蛋白含量显著增加，肾小球基底膜增厚，足细胞nephrin、podocin表达显著减少，通过厄贝沙坦干预治疗，上述指标改善（P〈0．05），且蛋白尿的程度与nephrin、podocin表达呈负相关（P〈0．05）。结论厄贝沙坦可通过拮抗DN大鼠的足细胞损害；减少其尿蛋白。

Objectives This research aims to study the mechanism of action of Irbesartan in treating proteinuria in diabetic nephmpathy （DN）. Methods DN rat models were preptued with an intraperitaneal injection, which were then randomly divided into model group （M group） and Irbesartan group （I group）. There was also a normal control group （C group）. After 12 -week intervention, the following tests and measures were carried out for each group： （ 1 ） Blood glucose, serum creatinine （ Cr）, blood urea nitrogen （BUN） and 24 - hour urine protein level tests; （2） Pathological tests, immunohistochemistry （IHC） and electron microscopy analyses; （3） Quantitative real - time liT - PCR. Results Noticeably increased 24 - hour urine protein levels and glomerular basement membrane （GBM） thickness and noticeably decreased expression of nephrin and podocin in podocytes were found in M group compared to C group. Irbesartan intervention improved the above indicators （ P 〈 0. 05 ）. Furthermore, the severity of proteinuria was found to be negatively correlated with nephrin expression and podocin expression（ P 〈0. 05）. Conclusions Irbesartan is able to lower the urine protein level by inhibiting damage to podocytes in DN rats.