Aminoguanidine Induced Up-Regulation of Sphingosine-۱ Phosphate Receptor-۱ (S۱PR۱) in Heart Tissue of Diabetic Rats

Background & Objective:  Cardiac microvascular complications are a significant concern in diabetes, often related to dysfunction of the sphingosine-۱-phosphate receptor-۱ (S۱PR۱). Aminoguanidine (AG) is recognized for its capability to alleviate these complications by inhibiting advanced glycation compounds and enhancing vascular function in diabetic rats. Therefore, this study seeks to investigate the therapeutic potential of AG by assessing its impact on the gene expression of S۱PR۱ in the heart tissue of diabetic rats.  Materials & Methods:  Thirty-four diabetic and healthy rats were stratified into eight groups, including diabetic rats, diabetic rats administered with varying doses of AG ۵۰, ۱۰۰, and ۲۰۰ mg/kg, healthy rats treated with the same AG doses, and untreated healthy controls. RNA extraction and cDNA synthesis were performed using heart tissue samples, followed by real-time PCR analysis. The fold change in S۱PR۱ gene expression was then assessed and compared among diabetic rats treated with varying AG doses and their corresponding control groups. Results: The analysis demonstrated a significant reduction in S۱PR۱ gene expression in diabetic rats compared to controls. However, AG treatment improved S۱PR۱ expression, which was correlated with the administered dose, with a notable upregulation observed in rats treated with ۲۰۰ mg/kg of AG compared to other groups (P<۰.۰۰۱). Conclusion:  Considering the significance of the S۱PR۱ pathway in inhibiting microangiopathy, augmenting S۱PR۱ gene expression through AG treatment may hold promise in preventing diabetes-related cardiovascular complications.

کلیدواژه ها:

Sphingosine-۱-Phosphate Receptor-۱ (S۱PR۱) ، Aminoguanidine ، Diabetes ، Cardiovascular Complications