微小RNA与他克莫司治疗相关性的研究进展

Research progress on the correlation between miRNAs and tacrolimus

他克莫司治疗窗窄,个体间的药动学/药效学差异较大。以往研究表明临床指标和遗传因素可能是影响他克莫司剂量选择的重要因素,但这对个体差异的解释仍有限。近年来,微小RNA(miRNA)作为一种潜在的生物标志物和特异性治疗靶点受到广泛关注,该文汇总分析了与他克莫司代谢相关的miRNA研究进展,期望能够为该药临床个体化用药研究提供新的思路。目前关于miRNA与他克莫司相关性的研究,以miRNA对CYP3A5的影响居多,涉及miR-29a-3p、miR-99a-5p、miR-532-5p、miR-500a-5p等;与CYP3A4表达相关进而影响他克莫司药动学的miRNA,如miRNA-627-5p;作用于钙调磷酸酶进而影响他克莫司体内作用的miRNA,如miR-582-5p;肾移植患者尿液外泌体中与他克莫司剂量呈正相关的miRNA,如miR-155-5p和miR-223-3p,但这两种miRNA通过何种途径影响他克莫司浓度尚未阐明;可能与他克莫司体内不良反应相关的miRNA,如miR-26b、miR-145、miR-183、miR-21-5p,miR-199a-5p和miR-214-3p、miR33a有关。研究提示,miRNAs能够在预测他克莫司疗效和不良反应方面提供新的生物标志物和干预靶点。

Tacrolimus has a narrow therapeutic window and large inter-individual differences in PK/PD.Previous studies have shown that clinical indicators and genetic factors may be important factors affecting tacrolimus dosage selection,but the interpretation of individual differences is still limited.In recent years,miRNA,as a potential biomarker and a specific target,has attracted wide attention.This article summarizes and analyzes the research progress of miRNA related to Tacrolimus metabolism,hoping to provide new ideas for clinical individualized drug research.The current research on the correlation between miRNA and tacrolimus showed that miRNA including miR-29a-3p,miR-99a-5p,miR-532-5p,miR-500a-5p mainly affected the expression of CYP3A5;miRNAs such as miRNA-627-5p could affect the expression of CYP3A4 and thus affect the pharmacokinetics of tacrolimus;miRNAs,such as miR-582-5p may affect the action of tacrolimus by calcineurin.The expression of miR-155-5p and miR-223-3p in the urine exosomes of kidney transplant patients is positively correlated with the dosage of tacrolimus,but the specific mechanism by which these two miRNAs affect tacrolimus concentrations has not been elucidated;miRNAs,such as miR-26b,miR-145,miR-183,miR-21-5p,miR-199a-5p,miR-214-3p,and miR33a may be involved in tacrolimus adverse reactions.The above research suggested that miRNAs can provide new biomarkers and intervention targets in predicting the efficacy and adverse reactions of tacrolimus.