Kallistatin抗炎作用的研究进展

The research progress of the anti-inflammatory effect of kallistatin

Kallistatin(KS)是一种激肽释放酶结合蛋白(kallikrein-binding protein),广泛分布于多种组织及体液中。KS不但具有抑制组织型激肽释放酶的作用,还具有抗炎、抗血管生成、抗肿瘤等多种生物学作用。KS生物学功能与其分子结构中不同的结构域有关。而KS抗炎作用被认为主要与肝素结合结构域有关。KS通过其肝素结合结构域,能竞争性抑制肿瘤坏死因子(tumor necrosis factorα,TNF-α)与它的受体的结合,从而起到影响TNF-α-NF-κB信号通路,发挥抗炎作用。K S也能与Kr uppel样因子4(Kr uppel-li ke Factor 4,KLF4)结合,激活内皮型一氧化氮合酶(endothelial nitr ic ox ide synthase,e NOS),抑制TNF-α活化核因子-κB(nuclear factor-κB,NF-κB),发挥抗炎作用。但这与肝素结合结构域的机制不同。不同的机制可能为抗炎治疗提供新的思路,本文将就Kallistatin抗炎作用的相关研究进展进行阐述。

Kallistatin（KS） is a kallikrein-binding protein,which is widely distributed in multiple tissues and body fluids.KS not only has inhibitory effect to tissue kallikrein,but also has anti-inflammatory anti-angiogenesis,anti-tumor and other biologic functions.The biologic function of KS is related to its molecular structure,which has different structural domains.The anti-inflammatory effect of KS is considered to be mainly related to the heparin-binding domain.Through this domain,KS can competitively inhibit tumor necrosis factor（TNF-α） combined with its receptors,and influence TNF-α-NF-κB signal pathway,contribute to anti-inflammatory effect.KS can also combine with Kruppellike Factor 4（KLF4）,activating endothelial nitric oxide synthase（eNOS）,as well as suppress TNF-α-induced nuclear factor-KB（NF-κB） activation,contribute to anti-inflammatory effect.But this mechanism is different from the mechanism of heparin-binding domain.Different mechanisms may provide a new idea for the anti-inflammatory treatment.This review focuses on the latest research progress in the anti-inflammatory effect of KS.