Interaction of miR-۱۴۶a-۵p with oxidative stress and inflammation in complications of type ۲ diabetes mellitus in male rats: antioxidant and anti-inflammatory protection strategies in type ۲ diabetic retinopathy

Objective(s): This study aimed to evaluate the role of miR-۱۴۶a-۵p in the pathogenesis of diabetic retinopathy and its interaction with oxidative stress and inflammation in the ocular tissue of rats with type ۲ diabetes mellitus (T۲DM). Materials and Methods: Twenty adult male Sprague Dawley rats (۲۲۰ ±۲۰ g) were randomly assigned to control and diabetic groups. A high-fat diet was used for three months to induce T۲DM which was confirmed by the HOMA-IR index. After that, the levels of glucose and insulin in serum, HOMA-IR as an indicator of insulin resistance, the ocular level of oxidative markers, TNF‐α, IL-۱β, MIPs, and MCP-۱ along with ocular gene expression of NF-κB, Nrf۲, and miR-۱۴۶a-۵p were evaluated.Results: The level of lipid peroxidation along with metabolic and inflammatory factors significantly increased and the antioxidant enzyme activity significantly decreased in diabetic rats (p <۰.۰۵). The ocular expression of NF-κB and TNF-α increased and Nrf۲, HO-۱, and miR-۱۴۶a-۵p expression decreased in diabetic rats (p <۰.۰۵). In addition, a negative correlation between miR-۱۴۶a-۵p expression with NF-κB and HOMA-IR and a positive correlation between miR-۱۴۶a-۵p with Nrf۲ were observed.Conclusion: It can be concluded that miR-۱۴۶a-۵p may regulate Nrf۲ and NF-κB expression and inflammation and oxidative stress in the ocular tissue of diabetic rats.

کلیدواژه ها:

Diabetic retinopathy ، Inflammation ، MicroRNA ، Oxidative stress ، Type ۲ diabetes