Mechanisms of action of mycophenolate mofetil
Mechanisms of action of mycophenolate mofetil
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DOI：
10.1191/0961203305lu2109oa
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发表时间：
2005-01-01
期刊：
影响因子：
2.6
通讯作者：
Allison, AC
中科院分区：
文献类型：
--
作者：
Allison, AC
霉酚酸酯（Mycophenolate mofetil， MMF, CellCept (R)）是肌苷-5′-单磷酸脱氢酶抑制剂霉酚酸（MPA）的前药。MPA在T淋巴细胞和B淋巴细胞中优先消耗鸟苷核苷酸并抑制其增殖，从而抑制细胞介导的免疫反应和抗体的形成。MPA还抑制粘附分子的糖基化和表达，以及淋巴细胞和单核细胞向炎症部位的募集。MPA消耗四氢生物蝶呤，减少诱导型NO合成酶产生一氧化氮，但不影响组成型NO合成酶的活性。活化的巨噬细胞产生一氧化氮和超氧化物，两者结合产生损伤组织的过氧亚硝酸盐。MMF通过这两种机制发挥抗炎活性。与钙调磷酸酶抑制剂不同，MMF没有肾毒性，也不会诱导TGF β的产生，而TGF β是纤维化的。MMF不会增加接受者的血压、胆固醇水平或甘油三酯水平。MMF可减少同种异体移植受者的急性和慢性排斥反应，对某些肾病有效。越来越多的证据表明MMF可能在某些自身免疫性疾病中具有临床应用价值。
Mycophenolate mofetil (MMF, CellCept (R)) is a prodrug of mycophenolic acid (MPA), an inhibitor of inosine-5'-monophosphate dehydrogenase. MPA depletes guanosine nucleotides preferentially in T and B lymphocytes and inhibits their proliferation, thereby suppressing cell-mediated immune responses and antibody formation. MPA also inhibits the glycosylation and expression of adhesion molecules, and the recruitment of lymphocytes and monocytes into sites of inflammation. MPA depletes tetrahydrobiopterin and decreases the production of nitric oxide by inducible NO synthase without affecting the activity of constitutive NO synthases. Activated macrophages produce NO and superoxide, which combine to generate tissue-damaging peroxynitrite. By these two mechanisms MMF exerts anti-inflammatory activity. Unlike calcineurin inhibitors, MMF is not nephrotoxic and does not induce the production of TGF beta, which is fibrogenic. MMF does not increase blood pressure, cholesterol levels or triglyceride levels in recipients. MMF reduces acute and chronic rejection in allograft recipients and is efficacious in some nephropathies. Evidence is accumulating that MMF may have clinical utility in some autoimmune disorders.