Effect of aminoguanidine on plasminogen activator inhibitor-1 and receptor of advanced glycation endproduct in the liver of streptozotocin-induced diabetic rats

Acta Biochimica Iranica Pub Date : 2024-01-20 DOI:10.18502/abi.v1i4.14720

Amirhossein Sangdari, Amir Karbalaee-Hasani, Mojtaba Fathi, Hadi Khodabandehloo

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Abstract

Objectives: Advanced glycation end products (AGEs) play an important role in the development and progression of diabetic complications. The receptor for AGE (RAGE) is the ligand-binding site of AGE that initiates and accelerates the atherosclerotic process. Plasminogen activator inhibitor-1 (PAI-1) is a prothrombotic factor that has been proposed as a biological marker for prognostic assessment, monitoring of microvascular and macrovascular complications in diabetes. The purpose of this study is to investigate the effects of aminoguanidine on RAGE and PAI-1 expression levels in the liver of streptozotocin-induced diabetic rats. Methods: Diabetes was induced in rats by intraperitoneal injection of streptozocin (STZ, 50 mg/kg). On day 3, diabetic rats were administered 50, 100, and 200 mg/kg/day of aminoguanidine. The expression of PAI-1 and RAGE in the liver tissue was evaluated using real-time PCR. Results: PAI-1 and RAGE gene expression levels were higher in the liver of the diabetic rats compared to the control group. Aminoguanidine at 50, 100, and 200 mg/kg decreased PAI-1 and RAGE gene expression in the liver (p<0.001 at all doses). However, these genes were downregulated only at a dose of 200 mg/kg in healthy rats (p<0.0001). In addition, hepatic AGE protein levels were significantly decreased following treatment of the diabetic rats with aminoguanidine (p<0.001). There was also a significant correlation between AGE protein concentration and the expression of PAI-1 and RAGE. Conclusion: In summary, the data of the present study suggest that aminoguanidine reduced the expression of PAI-1 and RAGE in the liver of the diabetic rats.

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氨基胍对链脲佐菌素诱导的糖尿病大鼠肝脏中纤溶酶原激活物抑制剂-1和高级糖化终产物受体的影响

目的：高级糖化终产物（AGEs）在糖尿病并发症的发生和发展过程中起着重要作用。AGE 受体（RAGE）是 AGE 的配体结合位点，它启动并加速了动脉粥样硬化过程。血浆蛋白酶原激活物抑制剂-1（PAI-1）是一种促血栓形成因子，已被提议作为糖尿病预后评估、微血管和大血管并发症监测的生物标志物。本研究旨在探讨氨基胍对链脲佐菌素诱导的糖尿病大鼠肝脏中 RAGE 和 PAI-1 表达水平的影响。研究方法通过腹腔注射链脲佐菌素（STZ，50 mg/kg）诱导大鼠患糖尿病。第 3 天，分别给糖尿病大鼠注射 50、100 和 200 毫克/千克/天的氨基胍。使用实时 PCR 评估肝组织中 PAI-1 和 RAGE 的表达。结果显示与对照组相比，糖尿病大鼠肝脏中 PAI-1 和 RAGE 基因表达水平较高。氨基胍的剂量为 50、100 和 200 mg/kg，可降低肝脏中 PAI-1 和 RAGE 基因的表达（所有剂量下的 p<0.001）。然而，只有在剂量为 200 毫克/千克时，健康大鼠的这些基因才会下调（p<0.0001）。此外，用氨基胍治疗糖尿病大鼠后，肝脏 AGE 蛋白水平明显下降（p<0.001）。AGE 蛋白浓度与 PAI-1 和 RAGE 的表达也有明显的相关性。结论总之，本研究的数据表明，氨基胍降低了糖尿病大鼠肝脏中 PAI-1 和 RAGE 的表达。

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Acta Biochimica Iranica

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