Significance Of NFAT Regulated Gene Expression In The Tacrolimus Pharmacodynamics Monitoring

Objective:To establish a method for determining the NFATc1、IL-2、IFN-γ、GM-CSF mRNA in human plasma by Real-time qPCR.To analysis the NFATc1、IL-2、IFN-γ、GM-CSF mRNA expression in the renal transplantation with rejection and infection reaction through experiment,and analysis the NFATc1、IL-2、IFN-γ、GM-CSF mRNA expression when rejection or infection reaction in patients reversed.To combine study tacrolimus(TAC) blood drug concentration and establish the tacrolimus pharmacodynamics(PD)correlation studies. Methods:1. Determining the establishment of tacrolimus pharmacodynamics monitoring method:The real-time qPCR method was used,to detect renal transplantation patients of NFATc1、IL-2、IFN-γ、GM-CSF mRNA expression.2. The relationship between NFAT regulated genes and renal transplantation patients with rejection:To detect 20 patients with rejection after renal transplantation of NFATc1 、 IL-2 、 IFN-γ 、 GM-CSF mRNA expression,and detect the mRNA expression of NFATc1、IL-2、IFN-γ、GM-CSF after treatment.3. The relationship between NFAT regulated genes and renal transplantation patients with infection: To detect 20 patients with infection after renal transplantation of NFATc1 、 IL-2 、 IFN-γ 、 GM-CSF mRNA expression,and detect the mRNA expression of NFATc1、IL-2、IFN-γ、GM-CSF after treatment.4. Correlation studies with tacrolimus pharmacodynamics in renal transplantation patients: To detect 20 patients with rejection and 20 patients with infection after renal transplantation of NFATc1、IL-2、IFN-γ、GM-CSF mRNA expression,and the relationship with tacrolimus blood concentration. Results:1. Determining the genes expression of NFAT regulated gene can be used to TAC pharmacodynamics monitor.The established method is rapid 、 simple and sensitive,can be used in clinical detection.2. The patients with rejection,the NFATc1、IL-2、IFN-γ、GM-CSF mRNA expression significantly reduced(P<0.05)after treatment.These data support that NFATc1 mRNA detection diagnosis effect is better than the other three kinds of gene diagnosis effect.3. The patients with infection,the NFATc1、IL-2、IFN-γ、GM-CSF mRNA expression significantly increased(P<0.05)after treatment.Thses data support that GM-CSF mRNA detedtion diagnosis effect is better than the other three kinds of gene diagnosis effect.4. According to the result of blood concentration detection, The patients with chronic rejection and infection before treatment and after treatment has significantly different.But TAC blood concentration with NFAT regulated gene expression has no significant correlationship. Conclusions:1. The established method is simple,fast and reliable.Patients after renal transplantation,the NFAT regulated gene expression significantly increased has closely related to rejection.2. Patients after renal transplantation,the NFAT regulated gene expression significantly decreased has closely related to infection.3. Monitoring the NFAT regulated gene espression of patients after renal transplantation can be used to predict the rejection and infection.