Long Hai-bo, Niu Hong-xin, Li Xiao-yun, Zhou Wei-dong, He Jing-hua, Zhong Juan, Wei Lian-bo
Nephropathy Center of Integrated TCM and Western Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2009 Dec;29(12):2433-6, 2441.
To investigate the effect of irbesartan on the renal expressions of advanced glycation end products (AGEs) and their receptor (RAGEs) in rats with early diabetic nephropathy (DN) and the renoprotection mechanism of irbesartan.
Rat DN models established by a single injection of streptozotocin were randomly divided into the model group and irbesartan treatment group. With normal rats as the control, all the rats received daily gavage for 8 weeks. The 24-h urinary protein excretion and contents of AGEs in the serum and kidney tissues were measured. The expressions of RAGEs and RAGEs protein and mRNA in the kidney tissues were detected by immunohistochemistry and reverse transcription-polymerase chain reaction, respectively. The pathological changes of the kidney were also assessed microscopically.
Irbesartan significantly reduced the 24-h urinary protein excretion and the contents of AGEs in the serum and kidney tissues of DN rats, resulting also in decreased expressions of RAGEs and RAGEs protein and mRNA levels in the kidney. The treatment obviously alleviated the pathological changes in the kidney of the DN rats.
Irbesartan offers renoprotection against DN possibly by reducing the serum and renal contents of AGEs and inhibiting the renal mRNA expressions of RAGEs and RAGEs.
探讨厄贝沙坦对早期糖尿病肾病(DN)大鼠肾脏晚期糖基化终产物(AGEs)及其受体(RAGEs)表达的影响以及厄贝沙坦的肾脏保护机制。
通过单次注射链脲佐菌素建立大鼠DN模型,随机分为模型组和厄贝沙坦治疗组。以正常大鼠作为对照,所有大鼠每日灌胃给药8周。检测24小时尿蛋白排泄量以及血清和肾组织中AGEs的含量。分别采用免疫组织化学和逆转录-聚合酶链反应检测肾组织中RAGEs及RAGEs蛋白和mRNA的表达。同时镜下评估肾脏的病理变化。
厄贝沙坦显著降低DN大鼠24小时尿蛋白排泄量以及血清和肾组织中AGEs的含量,同时使肾组织中RAGEs及RAGEs蛋白和mRNA水平的表达降低。该治疗明显减轻了DN大鼠肾脏的病理变化。
厄贝沙坦可能通过降低血清和肾脏中AGEs的含量以及抑制肾脏中RAGEs及RAGEs的mRNA表达而对DN起到肾脏保护作用。