炉甘石中的锌对拔毒生肌散中汞成分所致肾损伤的保护作用及其机制研究

The adverse effects,mainly hepatic and renal damage,as a result of clinical application of Traditional Chinese Medicine containing mercury, can not be igored. Combining applicationx of zinc and mercury can alleviate renal damage caused by mercury ,but the underlying mechanism is not clear.It is well known that oxidative stress is one of mechanisms through which mercury exert its toxic effects on its target organs while zinc is antioxidant ,and can reduce mercuric accumulation in kidney.Based on the above,We hypothesized that : Zinc may alleviate renal damage by inhibiting production of reactive oxygen species(ROS) induced by mercury ,exerting its effects on the activation of MAPKs signaling transduction pathway to affect the expression of some transporters such as P-glycoprotein (P-gp),multidrug resistance -associated protein(MRP),organic anion transporters (OATs) and organic cation transporters (OCTs) in renal proximal tubular cells,consequently increasing mercuric elimination or inhibiting mercuric reabsorption in renal proximal tubular cells.we intend to calrify the mechanisms of zinc reducing mercuric toxicity ,and to provide a novel scientific evidence for clinical retional application of Traditional Chinese Medicine containing mercury.

含汞中药在临床上引起的不良反应不容忽视，主要引起肝肾的损伤。而含有碳酸锌的炉甘石与含汞中药的配伍可明显减轻汞的肾毒性，但具体机制尚不清楚。已知氧化应激是汞的毒性作用机制之一，而锌不仅具有抗氧化作用，还能减少肾中汞的蓄积，因此我们提出假设： 锌可能通过抗氧化机制抑制了汞诱导的活性氧类(ROS)的产生，进而影响了MAPKs信号通路的激活，引起肾近端小管上皮细胞中与汞转运有关的转运体P-gp、MRP、OATs和OCTs的表达发生了变化，结果导致汞在肾小管的排泄增强或肾小管对汞的重吸收减弱，最终减轻了汞对肾的毒性损伤。我们拟从抗氧化应激的角度阐明锌对汞肾毒性的减毒机制，为含重金属中药在临床上的合理配伍提供科学依据。