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Optimization Of A Mouse Model Of Lupus Induced By Campylobacter Jejuni-S131 Beneficial Effects Of TLREXIN On Lupus-like Mouse Model

Posted on:2015-04-24Degree:MasterType:Thesis
Country:ChinaCandidate:Y LuFull Text:PDF
GTID:2284330464959774Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
1. Optimization of a Mouse Model of Lupus Induced by Campylobacter jejuni-S131AIM:To optimize a mouse model of systemic lupus erythematosus (SLE) induced by Campylobacter jejuni-S131 (CJS131).METHODS:The mice were divided into 5 groups randomly:normal control, BCG (Bacille Calmette-Guerin) control, H37Ra (Mycobacterium tuberculosis H37Ra) control, CJS131+BCG model, CJS131+H37Ra model. Mice were immunized on day0 and boosted on dayl4, day21, day42 and then be sacrificed on day36, day54, day61 in turn. The level of organ index, anti-nuclear antibodies, total IgG and the degree of pathological lesions of kidney were evaluated.RESULTS:The mice immunized by CJS131 and FCA (no matter with BCG or H37Ra) had SLE like syndromes:the level of serum anti-nuclear antibodies and total IgG of model groups was higher than those of the control groups. The kidneys of model groups had pathological lesions. All the pathological changes persisted in the dynamic detection.CONCLUSION:CJS131 played a major role in inducing lupus in mice. Model groups immunized by CJS131 plus FCA both had pathological injury, no matter with BCG or H37Ra in FCA. The pathological syndromes in boosted mice can persist for a long time. This study can be used in screening of therapeutic medicine for SLE.2. Beneficial effects of TLREXIN on lupus-like mouse modelAIM:To study the beneficial effects of TLREXIN on lupus-like mouse model induced by Campylobacter jejuni-S131.METHODS:Mice were divided into 7groups randomly,10 mice each group:normal control (A group:NS), model control (B group:FCA), CJS131 model (C group:FCA+CJS131), TLREXIN 50μg·kg-1 s.c. (D group:TLREXIN50+FCA+CJS131, s.c.), TLREXIN 100μg·kg-1 s.c. (E group:TLREXIN100+FCA+CJS131, s.c.), TLREXIN 50μ·kg-1 i.p. (F group:TLREXIN50+FCA+CJS131, i.p.), TLREXIN 100μg·kg-1 i.p. (G group: TLREXIN100+FCA+CJS131, i.p.). Mice were immunized on dayO and then boosted on day14, day42. TLREXIN 50 or 100·kg-1 were given to BALB/c mice on day 17, day 22, day 27, day 32, day 37, day 42, day 47 and day 52 respectively, s.c. or i.p.. Mice were sacrificed on day34 and day54 in turn. The levels of weight, spleen index, thymus index, liver index were measured. Serum samples of mice were tested by enzyme-linked assays (ELISA) for the presence of anti-nuclear antibodies, anti-dsDNA antibodies and creatinine. Urine protein was measured and kidneys were examined by light microscopy and graded by pathologist.RESULTS:1. Effect of TLREXIN on body weight and organ indexImmunization and boost injection caused weight loss in mice of model control group, model group and TLREXIN groups compared with the mice of normal group. Mice were fasted before sacrificed for 24 hours to collect urine which caused transient weigh loss on day 34 and day54.The index of spleen and thymus increased significantly in model group when compared with normal group and model control group (P<0.05). The index of liver was almost at the same level. TLREXIN had no significant effects on organ index in mice when compared with model group.2. Effect of TLREXIN on serum anti-nuclear antibodies and anti-dsDNA antibodiesThe level of serum anti-nuclear antibodies and anti-dsDNA antibodies of mice in model group increased significantly when compared with normal group and model control group (P<0.001). TLREXIN can reduce anti-nuclear antibodies of mice in group E, F and G when compared with model group to some extent but the data had no significant difference.3. Effect of TLREXIN on renal histologyThe level of urinary protein and creatinine increased when compared with model control group. The urinary protein and creatinine of mice were reduced by TLREXIN when compared with model group. The data had no significant difference.Observed with optical microscope, all mice of model group had significant symptoms such as kidney injury, mesangial cell proliferation, mesangial thickening and glomerular swelling etc. These changes were not observed in mice of normal group and model control group which suggested TLREXIN had obvious beneficial effect on renal pathological injury.CONCLUSION:The data of study suggested that TLREXIN had beneficial effects on SLE-like syndromes induced by CJS131 in BALB/c mice.
Keywords/Search Tags:Campylobacter jejuni-S131, Freund’s complete adjuvant (FCA), Systemic Lupus Erythematosus (SLE), TLREXIN, Inhibitory oligodeoxynucleotide (INH-ODN), Toll like receptors
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