The Therapeutic Effects Of Pentapeptide Compound PLNPK On Systemic Lupus Erythematosus(SLE) And Its Mechanisms

Objective:To investigate the therapeutic effect of pentapeptide compound PLNPK on systemic lupus erythematosus(SLE)and its possible mechanism.Methods:1.(DBA/2×C₅₇BL/J6)F1 hybrid mice were used as recipients of DBA/2 donor lymphocytes which were injected intravenously to induce SLE.They were divided into five groups:PLNPK(100,200,400μg/kg/d),saline control and normal control.From 15^thdays of the first injection,mice were given drugs.The effect of PLNPK on urine protein,renal index,serum ALB,TC,TG,BUN,Cr were detected;the effect of PLNPK on the pathology damage of kidneys were observed by HE colorization;the effect of PLNPK on ultramicrostructure of kidney were observed by Electron microscopy;the effect of PLNPK on deposits of IgG in kidneys were observed by immunofluorescence;the effect of PLNPK on anti-dsDNA antibody and anti-Histone antibody were observed by ELISA.2.The effect of PLNPK on T lymphocyte proliferation of SLE in vivo was assayed by MTS method.The effect of PLNPK on the infiltration and activation of T lymphocyte were assayed by CD₃ and C₂₅immunohistocemistry in the kidney tissue of SLE mice.The inhibiting effect of PLNPK on the proliferation of Jurkat T was assayed by MTS method.The effect of PLNPK(0.8,1.6mg/ml)on phospho-Zap-70 protein expression in Jurkat T and the effect of PLNPK on phospho-Zap-70 protein expression in SLE spleen cells were assayed by western blot.Results:1.PLNPK(100,200,400μg/kg/d)can decrease the urine protein(P＜0.05),kidney index(P＜0.05),serum TC and TG(P＜0.05).PLNPK(100,200μg/kg/d)can increase serum ALB(P＜0.05),decrease serum BUN(P＜0.05),it can also decrease anti-dsDNA antibody and anti-histone antibody(P＜0.05).PLNPK(100μg/kg/d) can decrease serum Cr(P＜0.05).HE stain revealed that PLNPK can ameliorate the pathological damage in kidneys of SLE.Immunofluorescence revealed that PLNPK can decrease deposits of IgG in kidneys.Electron microscopy revealed that PLNPK can decrease deposits of electron-dense material in the glomerular basement membrane and fusion of epithelial cell pod,it also can decrease the presence of wider basement membrane.2.PLNPK(100,200μg/kg/d)can significantly inhibit ConA induced T lymphocytes proliferation of SLE in vivo(P＜0.05).PLNPK can decrease the infiltration of CD₃⁺ T lymphocyte and CD₂₅⁺ T lymphocyte in kidneys of SLE. PLNPK(0.8,1.6,3.2mg/ml)can significantly inhibit T lymphocytes proliferation in vitro(P＜0.05).PLNPK(0.8,1.6mg/ml)can significantly inhibit phospho-Zap-70 protein expression in CD3 McAb induced Jurkat T lymphocytes (P＜0.05).PLNPK(100,200,400μg/kg/d)can significantly inhibit phospho-Zap-70 protein expression in SLE mice spleen cell.(P＜0.05).Conclusions:Pentapeptide compound PLNPK has the therapeutic effect on SLE.PLNPK can ameliorate renal function,decrease anti-dsDNA antibody and anti-histone body,relieve the pathological damage in kidneys of SLE and decrease the infiltration and activation of T lymphocyte in kidneys of SLE.PLNPK may exert its effect by inhibiting T lymphocyte proliferation and activation,PLNPK probably suppress the abnormal activation of T lymphocyte by inhibiting phospho-Zap-70 protein expression and its downstream signalling pathwaysin T lymphocyte.