Study On The Suppressive Effects Of Common Immunosuppressants On The Tibetan Monkey’s Immune System

Background: Tibetan primates(Macaca thibetana)are endemic animals of the genus Macaca in China,which has been widely used as a large animal model in medical research,while immunosuppressants such as FTY720,CSA,MMF and CVF have been widely used in clinical and experimental research,but there are few reports about their inhibitory effects on the Tibetan primate’s immune system.Objective: To establish immunosuppressive models of Tibetan primate monkeys using immunosuppressive agents such as FTY720,CsA,MMF and CVF.Evaluate methods and verify the effectiveness of joint expectations.Materials and methods: Adult male Tibetan primates were used as model animals.After consideration,the following techniques were used to detect relevant indicators:(1)Automatic blood cell analyzer and biochemical analyzer to detect hematology and blood biochemical indicators;Flow cytometry was used to detect T,B lymphocytes and macrophages;(3)High-performance liquid chromatography was used to detect plasma concentrations.After completing the single-drug study,effective immunosuppressive agents were screened based on the results of the study,and a combined biological transplantation regimen was simulated.We set up a combined program of preoperative induction therapy and alternative maintenance therapy to test relevant immune indicators.Results:(1)Pharmacodynamics and pharmacokinetics of FTY720.After the Tibetan primates were given different doses of FTY720 for three consecutive days,the lymphocytes of the Tibetan primates were significantly reduced(P <0.01),especially the CD3 + CD4 + T lymphocyte content was reduced by more than 90%,but liver and kidney function indicators and macrophages No significant change(P> 0.05).A single administration of 0.1 mg /(kg.d)FTY720 to the Tibetan primate monkey,the maximum blood concentration was 0.43 ± 0.064 ng / ml,the peak time was 12 ± 3 h,and the elimination half-life was 36 ± 12 h.(2)Pharmacodynamic study of CsA,MMF and CVF.After different doses of CsA were given to the Tibetan primate for three consecutive days,the mean values of hematological and blood biochemical indicators were not significantly changed(P> 0.05).After a single dose of 50 mg /(kg.d)of MMF,the Tibetan primate Lymphocytes were reduced by about 30% at most,but WBC and NEU were not significantly changed(P> 0.05).After a single administration of 0.05 mg /(kg.d)CVF to Tibetan primates,both C3 and CH50 in Tibetan primates were significantly reduced(P <0.01).(3)Study on the efficacy of combined prescription.After joint estimation,the lymphocyte content decreased significantly,T lymphocytes were almost completely cleared,and complement C3 and CH50 were significantly reduced.Conclusion: FTY720,MMF and CVF have inhibitory effects on the Tibetan primate immunosuppressive model.The research results show that FTY720,MMF and CVF have inhibitory effects on the Tibetan primate immunosuppressive model.This research can provide a reference for reconstructing immunosuppressive models and immune evaluations,and can provide a platform for drug mechanism exploration and new drug development,and it will help Tibetan primates in biological transplantation,human disease research and other medical applications.