PLNPK Ameliorated Experimental Systemic Lupus Erythematosus by Inhibiting the Activation of B Lymphocytes
|School||Tianjin Medical University|
|Keywords||PLNPK Systemic Lupus Erythematosus B lymphocytes CD23 CD40 B7-2|
Objective: To study the therapeutic effect of pentapeptide compounds PLNPK the mice with systemic lupus erythematosus (Systemic Lupus Erythematosus, SLE), and to explore its possible mechanism of action. Method: 1. Establish a mouse SLE model, were randomly divided into four groups: PLNPK (50, 100, 200 μg / kg / d) treatment group and the saline group, and the establishment of a normal control group. To observe PLNPK SLE model mice urine protein and kidney index, serum albumin (albumin, ALB), total cholesterol (total cholesterol, TC), triglycerides (triglycerides, TG), blood urea nitrogen (blood urea nitrogen, BUN), levels of creatinine (creatinine, Cr); observed by HE staining and immunofluorescence impact of PLNPK SLE mice renal pathological changes, and IgG deposition; measured by ELISA in the mice serum total IgG, anti-double stranded DNA (a double -stranded DNA, dsDNA) antibodies and anti-histone (histone) antibody levels observed inhibition of PLNPK mice autoantibodies generated. 2 the application hemolytic plaque assay PLNPK normal mouse spleen cells in B lymphocyte antibody-producing ability; detected by Western Blot and PCR methods, treated mouse spleen B lymphocyte activation marker CD23 protein and mRNA expression levels; using flow cytometry, PCR and Western Blot mouse spleen B lymphocyte costimulatory molecules CD40 and B7-2 expression were observed PLNPK SLE model mice spleen B lymphocyte activation in . Results: 1 PLNPK (50, 100, 200 μg / kg / d) can reduce the SLE mice urine protein and kidney index, reduce the model serum TC, TG, ALB level, and saline group P lt; 0.05; the the dose group PLNPK50μg/kg/d and 100μg/kg/d serum BUN Cr level was significantly lower than the saline group (P lt; 0.05); HE staining and immunofluorescence the results show PLNPK able to reduce SLE model mice glomerular degree of proliferation of mesangial cells, reduce a protein tube formation and renal interstitial inflammation cell infiltration, reducing kidney IgG deposition alleviate renal pathological damage; PLNPK can reduce SLE mice total serum IgG anti-dsDNA antibodies and anti-histone antibody levels, and compared to the saline group P lt; 0.05 2. PLNPK can effectively inhibit the normal mouse B cell antibody generation capability, down SLE model mice spleen cells of CD23 mRNA and protein expression levels, reduce spleen cell costimulatory molecules CD40 and B7-2 transcript and protein levels, and inhibition of CD40 and B7-2 expression on the cell membrane Conclusion: PLNPK mice SLE has a therapeutic effect, part of its mechanism may be by inhibition of B lymphocyte activation and costimulatory , CD40 and CD86 expression, reduce autoantibodies generated to reduce the deposition of immune complexes in the renal tissue, reduce the degree of T cell activation, thus alleviating renal tissue injury, restore the part of the kidney function.