Dong Yuan, Zhan Fang, Fang Sun, Jing Chang, Jian Teng, Shuhua Lin, Xiaoming Liu
Department of Nephrology, Yantaishan Hospital, Yantai, Shandong, China (mainland)
Med Sci Monit 2017; 23:3170-3177
To explore the effects and the mechanism of vitamin D (VD) and tacrolimus (TAC) combinatorial therapy in the treatment of IgA nephropathy (IgAN) in a rat model.
MATERIAL AND METHODS: IgAN rat models constructed by oral immunization with bovine serum albumin (BSA) and lipopolysaccharide (LPS) (n=30) and were treated with: saline (model group), TAC (TAC group), or TAC+VD therapy (TAC+VD group) through gavage daily for 14 days. Serum creatinine (Scr), albumin (ALB), blood urea nitrogen (BUN), and urinary protein (UAE) levels were determined. Histopathology of renal tissues was examined after hematoxylin and eosin (H&E) staining. The levels of cytokines TGF-β1, IL-5, IFN-γ, and IL-4 in serum were detected by enzyme-linked immunosorbent assay (ELISA). Changes in TLR4/NF-κB pathway were evaluated by western blot.
RESULTS: Both TAC and TAC+VD treatment significantly restored the dysregulated Scr, ALB, BUN, and UAE levels in IgAN rats. TAC+VD therapy more prominently restored Scr and UAE levels (p<0.05). TAC+VD therapy demonstrated superior efficacy in reducing glomerular mesangial cells hyperplasia, reducing thickening of the glomerular basement membrane and glomerular infiltration of inflammatory cells. Thymus and spleen indexes were also increased (p<0.05). The levels of TGF-β1, IL-5, and IL-4 of the TAC+VD group were also lower than those of the TAC group (p<0.05). The TAC+VD group also demonstrated increased IFN-γ, and decreased p-P65/P65 and TLR4 compared to the TAC group.
CONCLUSIONS: TAC+VD combinatorial therapy can effectively alleviate renal tissue damage in IgAN rats by regulating immune response and the NF-κB/TLR4 pathway.
Keywords: Calcitriol, Glomerulonephritis, IGA, Tacrolimus