Effects of 1,25-(OH)2-D3 on Oxidative Stress and Inflammation of Contrast

Abstract

Contrast-induced nephropathy (CIN) is a common complication of clinical diagnosis and treatment of coronary atherosclerotic heart disease. This study focused on the role of 1,25-(OH)2-D3 (D3) in contrast-induced renal tissue inflammation and oxidative stress. Thirty C57BL/6 mouse underwent unilateral renal pedicle ligation. One week after surgery, they were randomly divided into three groups, 10 mice in control group (CON group), 10 mice injected with iodixanol in contrast-induced nephropathy model group (CM group), 10 mice injected with contrast agent +in 1,25-(OH)2-D3 group (D3 group). The effects of 1,25-(OH)2-D3 on contrast nephropathy were studied by Hematoxylin-Eosin (HE) observation of kidney structure, detection of serum creatinine, urea nitrogen observation of kidney function, and Western blotting and quantitative reverse-transcription polymerase chain reaction (RT-PCR). Under the light microscope, the renal tissue structure of the CM group was disordered, hypertrophic glomeruli, renal tubular cells were significantly edematous, and the interstitial fibrosis area was significantly increased. The serum creatinine (SCr) and blood urea nitrogen (BUN) in CM group were significantly increased compared with CON group, the antioxidant proteins GPX1 and GPX3 were significantly decreased, while the apoptosis proteins Bax and Caspase-3 were significantly increased, and the anti-apoptotic protein Bcl-2 was significantly decreased. The expression of inflammatory factors IL-1β, IL-6 and TNF-α was significantly increased. However, the D3 can effectively inhibit apoptosis through inhibiting oxidative stress and inflammatory response. In addition, the expression levels of Toll Like Receptor 4 (TLR4) and /NF-κB-P65 in the D3 group were lower than those in the CM group. It is indicated that 1,25-(OH)2-D3 has an inhibitory effect on TLR4/NF-κB signaling pathway. 1,25-(OH)2-D3 can reduce contrast-induced SCr and BUN and alleviate renal structural damage by inhibiting the TLR4/NF-κB pathway, which has an effect of reducing inflammation, increasing tissue antioxidant levels, and delaying cellular senescence.