Effect Of Liposomal Quercetin On Systemic Lupus Erythematosus-like Mouse Model Induced By Pristane

Background and ObjectiveSystemic lupus erythematosus is a kind of autoimmune skin disease, with a high incidence, involving several systemic organs or tissues, the most frequently involved organ is the kidney. There are a variety of autoantibodies, including ANA, anti-dsDNA and anti-snRNP/Sm antibodies in serum. At present, the main drugs for SLE treatment are glucocorticoid, immunosuppressive agents, etc.The main functions of these hormones and immunosuppressive agents are to reduce the function of T and B lymphocytes, reduce the generation of specific autoantibodies, and inhibit the production of cytokines. But the drugs above will inevitably bring some serious side effects, such as inhibition of the reproductive system, increasing the tumor incidence, affecting the hematopoietic function and leading to the damage of the normal immune system. Nearly a hundred kinds of fruits, vegetables and Chinese herbal medicine contain a number of rich quercetin. The most important biological activities of Quercetin and its derivatives are the immune regulation and inflammation inhibition. Quercetin can also inhibit the complement over activation, regulate T cell activation and reduce the generation of autoantibodies. As a natural polyphenol compound, there are almost no toxicity, no side effects. Quercetin is superior to other drugs in disease control. Until now, there is no report on the treatment of SLE by liposome quercetin. By investigating the autoantibody levels and glomerular IgG deposition of the lupus mouse model, we are to explore the therapeutic effect of liposomal quercetin on SLE. Methods24 healthy BALB/c female rats, 6-8 weeks old, SPF, body weight 19±2 g, were randomly divided into 2 groups, namely the normal control group(n=6), the model group(n=18). Each mouse of the model group was given a single intraperitoneal injection of Pristane 0.5ml on the first day, while all the mice in the normal control group were injected with saline 0.5ml by intraperitoneal injection. At the end of third month, the antiserum levels of ANA in each mouse of the model group were detected to determine whether the model was successful or not. From the fourth month, all the successful model mice were randomly divided into two groups, namely model group(group SLE) and liposome quercetin group(group LQ), with the original normal control group(group NC), there were a total of three groups. All mice, marking by picric acid were fed with the whole nutrition pellet feed and the second class water for animal in IVC system of animal center of Henan Province during the whole course of the experiment. Dosing regimens: Mice in LQ group were given liposomal quercetin by gavage with 8# stomach needle at a dose of 50 mg·kg-1 body weight once a day. The treatment period was 5 months. At the end we collected all mice serum samples of three groups, and determine the expression levels of autoantibodies(ANA, anti-dsDNA, anti-snRNP/Sm) by ELISA test; while Fresh frozen sections of kidney were made, after dealing with IgG FITC fluorescent antibody, we observed fluorescence intensity of each sample under 525 nm fluorescence microscope and acquired images. ResultsAt the end of third month, there was one case died. There were fourteen mice of the modle group, whose antiserum levels of ANA increased significantly compared with the average level of NC group, p<0.05. At the end of eighth month, there were no deaths in all three groups. There were 4/7 mice(57%) of SLE group, 1/7 mice(14%) of LQ group, appeared erythema; there was no skin erythema in NC group, the rate of skin erythema in LQ group was lower than that of SLE group, p<0.05. The antiserum level difference of three groups, including ANA(24.535±1.297, 40.260±1.137, 34.180±0.817), Anti-dsDNA(355.793±17.562, 568.200±18.578, 475.930±14.237)and Anti-snRNP/Sm(14.802±0.824, 21.965±0.675, 18.970±0.376), was statistically significant(F=51.791, 39.745, 30.411, p<0.001). Compared with SLE group, the levels of autoantibodies in LQ group were significantly lower, p<0.01, but still significantly higher than those in NC group, p<0.001. Compared with SLE group, the glomerular IgG deposition of LQ group was significantly less, but was still more than that of NC group. ConclusionLiposomal quercetin could down-regulate the antoantibody levels of system lupus erythematosus-like mouse model induced by pristane, including ANA, Anti-dsDNA and Anti-snRNP/Sm antibody and reduce the glomerular IgG protein deposition, showed that liposomal quercetin has protective effect on systemic lupus erythematosus-like mouse model. It was expected to play a role in the treatment of human SLE.