| Objective:To investigate the therapeutical effect of pentapeptide PLNPK on the rats with anti-Thy1 MsPGN.To approach its probable mechanisms of inhibiting the activation of macrophages and the expression of IL-1βby affecting the p38 signal transduction pathway of macrophages.Methods:1.Anti-Thy1 MsPGN was induced in Wistar rats by an intravenous injection of anti-Thy1 serum.The effect of PLNPK on the kidney function of MsPGN was investigated through measuring the 24hrs urine protei,serum total protei,albumin,total cholesterol,triglyceride,urea nitrogen and creatinine of the rats with Anti-Thy1 MsPGN.The effect of PLNPK on immune complex deposition of kidneys in MsPGN was assayed through Immunofluorescence.The effect of PLNPK on the pathology damage of kidneys in MsPGN was assayed through HE stain and Masson stain.The effect of PLNPK on the Micro-structure of pathology damage of rats kidneys in MsPGN was assayed through transmission electron microscope.2.Anti-CD68 monoclonal antibody was used to observe the effction of PLNPK on the infiltration of macrophages in rats kidneys in MsPGN through immunohistochemistry method.Anti-CD86 monoclonal antibody was used to observe the effction of PLNPK on the activation of rats peritoneal macrophage through immunohistochemistry method.3.The effect of PLNPK on the expression of IL-1βin rats peritoneal macrophage activated by LPS was assayed through ELISA method.The effect of PLNPK on the expression of IL-1βmRNA in rats peritoneal macrophages activated by LPS was assayed through reverse transcription Real-Time PCR method.The effect of PLNPK on the phosphorylation of p38 kinase in rats peritoneal macrophage activated by LPS was assayed Western Blot method. Results:1.PLNPK can degrade the level of 24hrs urine protein since the 7thday after admistration(P＜0.05),and raise the level of serum total protein,albumin since the 28thday after admistration in anti-Thy1 MsPGN rats at dose of 100μg/kg/d and 200μg/kg/d(P＜0.05),but it can't affect the level of serum total cholesterol,triglyceride,urea nitrogen and creatinine(P＞0.05).PLNPK can reduce the formation of in-situ immune complex in kidney and reduce kidney pathological damage of anti-Thy1 MsPGN.2.PLNPK can reduce the infiltration of macrophages in rats kidney with MsPGN at dose of 100μg/kg/d and 200μg/kg/d.PLNPK can inhibit the activation of rats peritoneal macrophages stimulated by LPS at concentration of 6.4mg/ml,3.2mg/ml and 1.6mg/ml.3.PLNPK can inhibit the expression of IL-1βand IL-1βmRNA in rats peritoneal macrophages activated by LPS at concentration of 6.4mg/ml,3.2mg/ml and 1.6mg/ml(P＜0.05).PLNPK can inhibit the phosphorylation of p38 kinase in rats peritoneal macrophage activated by LPS at concentration of 6.4mg/ml,3.2mg/ml and 1.6mg/ml(P＜0.05).Conclusions:PLNPK can ameliorate the kidney function of rats with anti-Thy1 MsPGN, and degrade the level of 24hrs urine protein,raise the level of serum total protein,albumin,reduce kidney pathological damage.The mechanism maybe inhibit the infiltration and activation of macrophages,and reduce the expression of IL-1βin activated macrophages by inhibit the the phosphorylation of p38 kinase.
|
PDF Full Text Request