Protective effect of dexmedetomidine against renal injury in diabetic nephropathy rats through inhibiting NF-κB pathway

The aim of this study was to investigate the protective effect of dexmedetomidine (Dex) against renal injury in diabetic nephropathy (DN) rats by inhibiting the nuclear factor-κB (NF-κB) pathway.

A total of 36 Sprague-Dawley rats were randomly divided into three groups, including: normal group (n=12), model group (n=12) and Dex group (n=12). The rats underwent no treatment in normal group. In model group, the diabetes model was successfully established, and normal saline was intraperitoneally injected after operation. In Dex group, the diabetes model was established as well, and Dex was intraperitoneally injected after operation. After intervention for 2 weeks, the samples were taken for use. Blood urea nitrogen (BUN) and serum creatinine (Cr) were detected using a full-automatic biochemical analyzer. The expression of Caspase-3 was detected via immunohistochemistry. Western blotting was conducted to detect the protein expression of NF-κB. The apoptosis was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. In addition, the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were determined via enzyme-linked immunosorbent assay (ELISA).

The levels of BUN and Cr were significantly higher in model group and Dex group than those in normal group (p<0.05). However, they were significantly lower in Dex group than those in the model group (p<0.05). Immunohistochemistry results showed that the mean optical density of Caspase-3 positive expression increase remarkably in model group and Dex group when compared with normal group (p<0.05). However, it significantly declined in Dex group when compared with the model group (p<0.05). The results of Western blotting revealed that model group and Dex group exhibited evidently higher relative protein expression of NF-κB than normal group (p<0.05). However, Dex group displayed notably lower relative protein expression of NF-κB than model group (p<0.05). TUNEL assay demonstrated that the apoptosis rate increased significantly in the model group and Dex group when compared with normal group (p<0.05). However, it remarkably declined in Dex group in comparison with the model group (p<0.05). Finally, ELISA assay indicated that model group and Dex group had markedly higher levels of IL-6 and TNF-α than normal group (p<0.05). However, the levels of IL-6 and TNF-α were significantly lower in Dex group than model group (p<0.05).

Dex inhibits inflammation and apoptosis by suppressing the NF-κB signaling pathway, thereby exerting a protective effect against renal injury in DN rats.