| Objective To study the relationships between toxic pathogen and systemic lupus erythema-tosus(SLE), and curative effect and safety of the toxic medicine tripterygium wilfordii hook and arsenic on MRL/lpr mice, based on the therapuetic theory of traditional Chinese medicine,"to counteracting one toxin with another",in order to provide the basis for clinical application.Methods The first part is theoretical research, the method of literature research is to retrieve ancient books and journal articles, and systemic lupus erythematosus of toxin and toxic medicine Leigongteng, Pishuang literature were analyzed. The second part is experimental research,experimental study of the42MRL/lpr mice were randomly divided into model group, prednisone group, triptolide high/low-dose treatment group, arsenic trioxide high/low dose group of six groups, each treatment group the corresponding drug therapy for8weeks.Determination of survival, spleen index, liver and kidney function, using analysis of serum concentrations of anti-ds-DNA antibodies and IFN-y ELISA; using immune mouse urine concentrations of24h urine protein assay; HE renal pathology by frozen section immune fluorescence staining and pathological examination.observation MRL/lpr mice damage of the kidneys; The lymphocyte apoptosis rate was measured by flow cytometry.Results Theoretical research shows that SLE pathogenesis and clinical manifestations are associated with toxin factor, tripterygium wilfordii hook and arsenic cure SLE by combating poison with poison. The experiment research find that MRL/lpr lupus mice after8weeks of treatment intervention, model group and the high-dose group mice induced by arsenic trioxide large number of deaths, the rest of the group could improve the survival rate of mice. Spleen index, comparing low-dose prednisone group and arsenic trioxide with the model group decreased significantly, and the rest were no significant differences. Anti-ds-DNA antibody titers compared prednisone group and model group, low-dose triptolide group was significantly lower(P<0.05).Concentrations of IFN-y compared with the model group were each treatment group can reduce serum levels of IFN-y expression, and compared with the prednisone group, low-dose group triptolide significantly reduced expression of serum IFN-y level, there was a significant difference(P<0.01).24h proteinuria compared with the model group in each treatment group were lower than the model group, compared with the prednisone group, no significant difference(P>0.05).triptolide low-dose group. HE staining of renal pathology in the model group increased mesangial cells, mesangial matrix was significantly widened, segmental glomerular sclerosis, capillary endothelial cell proliferation, stenosis significantly, prednisone group compared with kidney disease management model group improved significantly. Immunofluorescence frozen section pathology display, model group and the high-dose group triptolide IgG, IgM and complement C3were strongly positive, along the back wall and glomerular mesangial capillary granular and lumpy deposition, the remaining each group has been eased.Apoptosis test results comparing each treatment groups showed significant difference with the model group(p<0.05).alanine aminotransferase compared with model group, triptolide significantly increased in high dose group were statistically significant(p<0.01).Serum creatinine and urea nitrogen compared with model group, low-dose group triptolide and arsenic trioxide low-dose group were reduced significantly (p<0.05), triptolide high-dose group significantly higher were statistically significant (p<0.05).Conclusion①The occurrence and development of SLE was closely related with the toxic pathogen, and triptolide and arsenic trioxide, the main components of the toxic medicine tripterygium wilfordii hook and arsec, triptolide and arsenic trioxide could be used to treat SLE.②Low dose (30ug/ml) of triptolid could significantly reduce mouse anti-ds-DNA antibody titers,24h proteinuria and have a protective effect on renal pathology. There was no obvious toxicity to the liver and kidney of the low dose but the high dose triptolid had severe toxicity.③Low dose (180ug/ml) of arsenic trioxide had significant inhibitory effect and could reduce the concentration of serum IFN-γ, with no apparenttoxicity to liver and kidney, however, there was significant weight loss in mice, and the mortality increased. High doses of arsenic trioxide(360ug/ml) led to the highest mortality rate, indicating with increasing dose and prolonging administration, side effects on MRL/lpr mice would increase.④Low dose of triptolide had better efficacy than high dose and high dose of arsenic trioxide, and it showed greater safety in MRL/lpr mice. |
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