TNFα-在小鼠叶酸诱导肾病中的致病作用及其机理研究

目的研究TNF-α在小鼠叶酸诱导肾病中的致病作用及其机制。方法建立小鼠叶酸诱导肾病模型,运用抗TNF-α多克隆抗体及对照抗体干预治疗,检测小鼠血清以及肾组织中TNF-α水平,肾小管上皮细胞凋亡情况以及凋亡相关蛋白的表达水平。结果在CD1小鼠叶酸诱导肾病模型中,尿素氮水平显著升高,肾小管上皮细胞坏死和凋亡增加,小鼠血清以及肾组织中TNF-α水平显著升高,肾皮质组织中Bcl-xL表达水平显著下降,运用抗TNF-α多克隆抗体干预治疗可保持Bcl-xL在肾组织中的表达水平,减少肾小管上皮细胞凋亡,有效减轻小鼠肾功能损害。结论TNF-α在小鼠叶酸诱导肾病发病机制中具有重要作用,阻断TNF-α是治疗急性肾衰的一种潜在有效手段。

The Role of Tumor Necrosis Factor-α in Folic Acid-induced Nephropathy and the Underlying Mechanism

Objective To study the role of tumor necrosis factor-αin folic acid-induced nephropathy(FAN) and the underlying mechanism.Methods FAN mouse model was established and treated with anti-TNF-α antibody.Results CD-1 mice treated with folic acid(FA) developed nephropathy characterized by increased blood urea nitrogen and apoptosis of tubular epithelial cells.Compared with control mice,tumor necrosis factor-α(TNF-α) was markedly elevated in blood and kidneys of these FA-treated mice,accompanied by markedly reduced expression of anti-apoptotic protein Bcl-xL in their kidneys.In vivo administration of FA-treated CD-1 mice with neutralizing anti-TNF-α antibody restored the expression of Bcl-xL in kidneys and inhibited the apoptosis of renal tubular epithelial cells,leading to the amelioration of nephropathy.Conclusion TNF-α is a critical inflammatory cytokine responsible for FA induced nephropathy,and in vivo blocking the role of TNF-α may be proved as an effective approach for prevention and treatment of acute renal failure.