Abstract: In this study, the effect of Lactococcus lactis subsp. lactis HFY14 (LLSLHFY14) isolated from naturally fermented yak yoghurt in Hongyuan county of Sichuan in improving renal function in mice with lupus nephritis induced by norphytane was investigated. The effects of different doses of LLSLHFY14 on immune indexes such as interleukin (IL)-2 and IL-12 were measured. Then, renal histopathology was observed by hematoxylin-eosin (H&E) staining, and the relative mRNA and protein expression of IL-4, IL-1β and transforming growth factor beta (TGF-β) in renal tissue were measured by quantitative polymerase chain reaction (qPCR) and Western blot. The results showed that LLSLHFY14 could increase thymus and spleen indexes in mice with lupus nephritis. LLSLHFY14 could inhibit the decrease in IL-2, IL-12, total protein (TP) and albumin (ALB) and the increase in interferon gamma (IFN-γ), transforming growth factor beta (TGF-β), immunoglobulin G (IgG), serum creatinine (SCr), blood urea nitrogen (BUN), total cholesterol (TC) and triglyceride (TG) in the serum of mice with lupus nephritis. LLSLHFY14 could also reduce the positive rate of anti-double stranded deoxyribonucleic acid (dsDNA) antibodies in mice caused by norphytane. Pathological examination showed that LLSLHFY14 could restore glomerular morphologic integrity and inflammatory infiltration in mice with lupus nephritis. Furthermore, LLSLHFY14 could up-regulate the expression of IL-4 and down-regulate the expression of IL-1β and TGF-β in the kidney. It can be concluded that LLSLHFY14 significantly improves renal function in mice with lupus nephritis in a positive concentration-dependent way. The effect of LLSLHFY14 at high concentration (109 CFU/kg) is close to that of prednisone. This study lays a foundation for further utilization of lactic acid bacteria in naturally fermented yak yogurt.

Key words: lupus nephritis; norphytane; immune; expression