Mechanism of Resatorvid Regulating KIM-1 Expression in Renal Tissues of Mice with Lupus Nephritis Through TLR4/MyD88 Pathway

TIAN Yu; DING Meng; YANG Yushu; GUO Huifang; HAN Yuxiang

doi:10.13730/j.issn.2097-2148.2025.05.004

Abstract：Objective To explore the effect of resatorvid on renal tissue injuries in lupus nephritis(LN)mice through the Toll-like receptor 4/myeloid differentiation primary response protein 88(TLR4/MyD88)pathway.Methods Sixty SPF-grade 8-week-old mice were divided into control group,LN group,LN+treatment group and LN+resatorvid group,with 15 mice in each.Except for the control group,the other 45 mice were intraperitoneally injected with 0.5 ml pristane to induce LN,after successful modeling,the mice in the LN+treatment group were intraperitoneally injected with0.5 mg/kg tacrolimus+50 mg/kg mycophenolate mofetil+1 mg/kg prednisone;mice in LN+resatorvid group were intra-peritoneally injected with resatorvid 3 mg/kg;mice in the control and LN groups were intraperitoneally injected with normal saline,the interventions were conducted among 4 groups once a day for 14 consecutive days.Renal function,cell apoptosis and TLR4/MyD88 pathway levels were compared among groups.Results The levels of creatinine(Cr),blood urea nitro-gen(BUN),the apoptosis index,as well as the protein expression of kidney injury molecule 1(KIM-1),TLR4 and MyD88 of the mice all significantly increased in the LN group compared to the control group(all P＜0.05);the levels of Cr,BUN,apoptotic index,as well as the protein expression levels of KIM-1,TLR4 and MyD88 in the LN+treatment group and the LN+resatorvid group were all lower than those in the LN group(all P＜0.05);the protein levels of KIM-1,TLR4 and MyD88 of the mice in the LN+resatorvid group were significantly lower than those in the LN+treatment group(all P＜0.05).Conclusion The TLR4/MyD88 pathway inhibitor resatorvid can alleviate LN induced renal tissue damage,thereby protecting renal function.