关键词: 姜黄素, 系统性红斑狼疮, 免疫紊乱, 肾损伤, 磷脂酰肌醇-3-激酶, 蛋白激酶B, 哺乳动物雷帕霉素靶蛋白

Abstract: Objective To explore the improvement effect of curcumin on systemic lupus erythematosus(SLE)in mice and analyze its mechanism.Methods Ten MRL/MpJ mice were used as the control group,while 40 MRL/lpr mice were randomly divided into four groups:the model group,the low-dose group,the high-dose group,and the combination group,with 10 mice in each group.The low-dose and high-dose groups were administered curcumin at doses of 250 mg/kg and 500 mg/kg,respectively,via oral gavage.The combination group received 500 mg/kg of curcumin via oral gavage along with an intravenous injection of 20 mg/kg of the phosphatidylinositol-3-kinase(PI3K)activator 740Y-P.After 8 weeks of continuous intervention,24-hour urinary protein,serum creatinine(Scr),and blood urea nitrogen(BUN)levels were measured.Serum levels of inflammatory factors[interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and interferon-γ(IFN-γ)]and autoantibodies[anti-small nuclear ribonucleoprotein(snRNP/Sm)and anti-doublestranded DNA(dsDNA)antibodies]were detected by using ELISA.Renal histopathological changes were observed by hematoxylin-eosin(HE)staining.Immunofluorescence was used to detect immune complex and complement deposition.Western blot was performed to assess the expression levels of CD4,CD19,CD20,PI3K,phosphorylated PI3K(p-PI3K),protein kinase B(Akt),phosphorylated Akt(p-Akt),mammalian target of rapamycin(mTOR),and phosphorylated mTOR(p-mTOR).Results Compared with the control group,the 24-hour urine protein,serum Scr and BUN levels,serum inflammatory factors(IL-6,TNF-α,IFN-γ),autoantibodies(anti-dsDNA,anti-snRNP/Sm),renal IgG and C3 deposition levels,and CD4,CD19,CD20,p-PI3K,p-Akt,p-mTOR protein expressions in the model group were significantly increased(all P<0.05).The above indicators in low and high dose groups were significantly lower,and the effect was more significant in the high-dose group.The indexs were significantly lower than that in the model group,and the effect in the high-dose group was more significant(all P<0.05).The above indexes in the combined group were higher than those in the high dose group(P<0.05).HE staining showed that the pathological changes of renal tissue in low and high dose groups were obviously improved,especially in high dose group,and the damage of renal tissue in combined group was more serious than that in high dose group.Conclusion Curcumin can ameliorate immune dysregulation and renal injury in SLE mice,potentially through the regulation of the PI3K/Akt/mTOR signaling pathway.

Key words: curcumin, systemic lupus erythematosus, immune dysregulation, renal injury, phosphatidylinositol-3-kinase, protein kinase B, mammalian target of rapamycin