Effect of fenofibrate on diabetic retinopathy in rats via SIRT1/NF-κB signaling pathway

N. Chen, K. Jiang, G.-G. Yan

Department of Ophthalmology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China. yhdyanguigang@163.com

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• Pharmacology

OBJECTIVE: To explore the influence of fenofibrate on the diabetic retinopathy (DR) in rats via the sirtuin1 (SIRT1)/nuclear factor-κB (NF-κB) signaling pathway.

PATIENTS AND METHODS: A total of 30 SD rats were divided into group A (DR group), group B (fenofibrate treatment group) and group C (Healthy group). Rats in group A were intraperitoneally injected with 50 mg/kg streptozotocin (STZ) for 5 days without feeding. After fasting for 2 days, blood was drawn from the tail veins of the rats to measure blood glucose, and blood glucose ≥16.7 mmol/L represented that the model was eligible. Those in group B were injected with STZ and nourished with the mixed feed containing fenofibrate (10 mg/kg). Those in group C were intraperitoneally injected with normal saline and set as negative control group. The retinal structure of rats in the three groups was observed via immunohistochemical staining, and the apoptosis of retinal ganglion cells (RGCs) was evaluated via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Moreover, the protein expressions of Sirtuin1 (SIRT1) and NF-κB were detected using immunofluorescence assay and Western blotting.

RESULTS: According to the immunohistochemical staining results, rats in group C had intact retinal nuclear layer tissues without phenomena such as fracture, disorderly arrangement, blur structures, and nerve fiber layer edema. Those in group A exhibited fracture of retinal nuclear layer tissues, disorderly arranged cells, blur retinal structures at all layers, and a quite evident nerve fiber layer edema. Compared to that in group A, the nerve fiber layer edema in group B was significantly improved. The TUNEL assay results revealed that compared to normal rats in group C, those in group A and group B had apoptotic RGCs. Additionally, the number of apoptotic cells was the largest in group A, and compared to that in group A, it was notably reduced in group B after treatment with fenofibrate. According to the immunofluorescence assay results, after being treated with fenofibrate, rats in group B showed a significantly lower protein expression level of NF-κB in the retina than in group A. Based on the Western blotting detection results, the protein expression level of NF-κB in group B was evidently lower than that in group A, and was the highest in group A and the lowest in group C. Compared to that in group C, the protein expression level of SIRT1 in group B was increased.

CONCLUSIONS: Fenofibrate facilitates the expression of SIRT1 in the retinal tissues to reduce the NF-κB activity, thereby treating DR in rats.

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