To investigate the effect and mechanism of all-trans retinoic acid in the mouse model of nephrotoxic serum nephritis (NTSN).

The NTSN model was constructed by tail vein injection of nephrotoxic serum (NTS), and the mice were divided into the control group, NTS group, and NTS+ retinoic acid group. Five days before the injection of NTS, goat immunoglobulin and complete Freund′s adjuvant were intraperitoneally injected as pretreatment. 24 h after the pretreatment, 16 mg/kg all-trans retinoic acid or dissolvant was intraperitoneally injected. 7 days after the NTS injection, the mice were sacrificed. The albuminuria/creatinine ratio and serum BUN of the mice were measured by ELISA. HE staining of paraffin sections of renal tissue was performed, and quantitative analysis was made of the percentage of crescentic and glomerular segmental sclerosis lesions. Frozen sections of renal tissue were stained with immunofluorescence for quantitative analysis of CD8⁺ , CD4⁺ and CD68. The QPCR method was used to analyze the expression levels of inflammatory cytokines such as human monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), and lymphotactin (LTN) in the renal cortex tissue.

Compared with the NTS group, the NTS+ retinoic acid group had significantly lower proteinuria. The urinary microalbumin/creatinine ratio (UACR) for NTS group and NTS+ retinoic acid group was (4.52±0.36)×10^-3mg/g, (2.63±0.18)×10^-3mg/g, respectively (q=18.45, P<0.01), while the BUN level for NTS group and NTS+ retinoic acid group was (16.81±1.23)mmol/L, (13.33±0.62) mmol/L; respectively (q=6.155, P<0.01). And the percentage of glomeruli with crescents in the NTS group and NTS+ retinoic acid group was 36.58% and 22.2%, respectively (q=21.46, P< 0.01). Compared with the NTS group, the NTS+ retinoic acid group had significantly smaller CD8⁺ lymphocyte count, CD4⁺ lymphocyte count, and area of CD68 positive cells (q value: 9.545, 8.610, and 11.08, respectively, P<0.01). The expression of MCP-1, ICAM-1, and LTN was significantly inhibited by retinoic acid.

Retinoic acid inhibited the expression of inflammatory chemokines, reduced the infiltration of inflammatory cells, and alleviated the renal damage such as proteinuria and crescent formation in the mouse model of nephrotoxic serum nephritis.