关键词: 系统性红斑狼疮, 狼疮性肾炎, 山柰酚, JAK2/STAT3信号通路, 肾损伤, 炎症因子

Abstract: BACKGROUND: Studies have found that kaempferol may be a potential drug for improving immune and inflammatory mechanisms in advanced diabetic nephropathy by affecting ferroptosis. The Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway exhibits high transcriptional activity in autoimmune diseases and inflammation.
OBJECTIVE: To investigate the effect of kaempferol against renal injury in mice with lupus nephritis.
METHODS: MRL/lpr mice (systemic lupus erythematosus mice) were randomly divided into model group (n=12), low-dose kaempferol group (n=12), medium-dose kaempferol group (n=12), high-dose kaempferol group (n=12), high-dose kaempferol+STAT3 activator group (n=12), and positive drug group (n=12). Twelve C57BL/6 mice were selected as the control group. The control and model groups received intragastric administration of normal saline. The low-, medium-, and high-dose kaempferol groups received intragastric administration of 25, 50, and 100 mg/kg kaempferol, respectively. The high-dose kaempferol+STAT3 activator group received intragastric administration of 100 mg/kg kaempferol combined with intraperitoneal injection of the STAT3 activator colivelin. The positive drug group received intraperitoneal injection of prednisone acetate. All administrations were performed once daily for 4 consecutive weeks. At 2 weeks after the final administration, the following parameters were measured: 24-hour urinary protein level, renal function indicators, serum inflammatory factor levels, renal histopathological morphology, IgG deposition in renal tissue, and protein expression of phosphorylated JAK2, JAK2, phosphorylated STAT3, and STAT3 in renal tissue.
RESULTS AND CONCLUSION: (1) Compared with the control group, the model group showed glomerular proliferation and sclerosis, peripheral inflammatory cell infiltration, increased IgG deposition, and significantly elevated levels of 24-hour urinary protein, serum creatinine, blood urea nitrogen, anti-double-stranded DNA, interleukin 6, tumor necrosis factor α, interleukin 1β, interleukin 17, and interleukin 23, along with upregulated protein expression of phosphorylated JAK2 and phosphorylated STAT3 (P < 0.05). (2) Compared with the model group, the low-, medium-, and high-dose kaempferol groups and the positive drug group showed gradually alleviated periglomerular inflammation, reduced IgG deposition, and significantly decreased levels of 24-hour urinary protein, serum creatinine, blood urea nitrogen, anti-double-stranded DNA, interleukin 6, tumor necrosis factor α, interleukin 1β, interleukin 17, and interleukin 23, along with downregulated protein expression of phosphorylated JAK2 and phosphorylated STAT3 (P < 0.05). (3) Compared with the high-dose kaempferol group, the high-dose kaempferol+STAT3 activator group showed increased periglomerular inflammatory cell infiltration, more IgG deposition, and significantly elevated levels of 24-hour urinary protein, serum creatinine, blood urea nitrogen, anti-double-stranded DNA, interleukin 6, tumor necrosis factor α, interleukin 1β, interleukin 17, and interleukin 23, along with upregulated protein expression of phosphorylated JAK2 and phosphorylated STAT3 (P < 0.05). Overall, these findings indicate that kaempferol may alleviate renal injury in mice with lupus nephritis by inhibiting the JAK2/STAT3 signaling pathway.

Key words: systemic lupus erythematosus, lupus nephritis, kaempferol, JAK2/STAT3 signaling pathway, renal injury, inflammatory factors