麦考酚酸体外对肝脏自然杀伤细胞活性及其受体表达的影响  

Effect of Mycophenolic Acid on Liver Resident NK Cells Activation in Vitro

作　　者：董帅[1] 蒋国平[1] 耿磊[1] 方云[1] 沈淼达[1] 陈耀敏[1] 郑树森[1] 

机构地区：[1]浙江大学医学院附属第一医院肝胆胰外科

出　　处：《中国药学杂志》2007年第8期589-592,共4页Chinese Pharmaceutical Journal

基　　金：国家重点基础研究发展计划资助课题(973计划)(2003CB515501)

摘　　要：目的探讨麦考酚酸(MPA)对肝脏自然杀伤(NK)细胞活性的影响及其机制。方法分离C57BL/6小鼠肝脏NK细胞,用不同浓度MPA处理24h后,3H-TdR释放法检测NK细胞杀伤活性,ELISA法检测培养上清IFN-γ,IL-2,IL-10含量,流式细胞术检测NK细胞受体NKG2D,NKG2A,Ly49A的表达情况。结果不同浓度MPA处理后肝脏NK细胞杀伤活性较正常对照明显降低(P<0.01),IFN-γ,IL-2分泌量降低,而IL-10分泌量增高,NK细胞活化性受体NKG2D和抑制性受体Ly49A的表达下调,抑制性受体NKG2A的表达上调,高浓度的MPA作用后结果更明显。结论MPA通过下调肝脏NK细胞活化性受体NKG2D并上调抑制性受体NKG2A而抑制肝脏NK细胞活性并影响细胞因子的分泌。OBJECTIVE To explore the effect of mycophenolic acid（MPA） on liver resident NK cells activation. METHODS After liver lavement, the hepatic lymphocytes of C57BL/6 mice were isolated and the NK cells were purified and cultured with different concentration MPA for 24 h. Then NK cells cytotoxicity was determined by [ ^3 H ] TdR release assay, the secretions of IFN-γ, IL-2 and IL-10 were measured by ELISA, and the expression of NK cell receptor NKG2D,NKG2A and Ly49A was measured by FACS. RESULTS After being cultured with MPA, the liver resident NK cells cytotoxicity was impaired with a dose-dependent manner, the secretion of IFN-γ and IL-2 was decreased while the secretion of IL-10 was increased, and the expression of the NK cell surface molecules NKG2D and Ly49A was down-regulated, but that of NKG2A was up-regulated. In high concentration MPA group（0. 1 mmol · L^-1 ）, the effect of mycophenolic acid on liver NK cell was most significant（ P 〈 0. 001 ）. CONCLUSION MPA inhibits the liver resident NK cells activation by down-regulating NKG2D and up-regulating NKG2A.

关 键 词：麦考酚酸 肝 自然杀伤细胞 

分 类 号：R965[医药卫生—药理学]