In recent years, lanthanides compounds for medical profession have been increasingly concerned ^[1-4]. Besides gadolinium incompatibility was widely used as imaging agents in nuclear magnetic resonance diagnose, lanthanum carbonate (trade name was Fosrenol ^R) was authorized going on the market by FDA to treat high phosphorus academia induced by renal failure in 2004. All of these increased the expectation of rare-earth for medical profession. However, some toxicity was also observed for these drugs ^[5-6]. Especially in the past several years, the heavy toxicity induced by Gd imaging agents in nuclear magnetic resonance also arise large attention on safety problems of using Ln for medical profession. E.g. incompatibility of Gd might cause nephrogenic systemic fibrosis ^[7]; in 2000, Briner etc. raised that Ln might cause behavioral teratogenesis according to the results of zoopery ^[8]. In 2007, Guliaev etc. raised that La³⁺ might pass through blood-brain barrier to protect ischemic neuron when brain was damaged ^[9]. Cheng etc. also reported that rare-earth enhanced erythrocyte membrane forming domain structure and “burrow”, so as to improve the permeability of membrane for Ln seeping into cell ^[10]. As Ln had shrinkage, their ion diameter decreased from La³⁺ to Lu³⁺ gradually. In fact, their biological effects always appeared significant difference. The principle of the effect of rare-earth element on peripheral nervous system was rarely studied, and the relation between the difference of chemical property of rare-earth and the difference of biological effect was also rarely understood regularly. Thus, we selected La³⁺, Gd³⁺, Yb³⁺, etc. as representative rare-earth to study its influence on neuron DRG on dorsal root.

The results showed that: apoptosis rate of cell increased without significant difference after neuron DRG was treated with LaCl₃ and GdCl₃ of 10, 100 and 1000 μmol/L for 96h; apoptosis rate of cell treated with three concentration groups of YbCl₃ for 96h increased and had significant difference compared with control group. La³⁺, Gd³⁺ and Yb³⁺ of 100μmol/L outside the cell inhibited the transient outward potassium current I_A and the activation as well as inactivation of I_A significantly shifted to the right, La³⁺ had weakest effect as well as Yb³⁺ had strongest effect; La³⁺, Gd³⁺ and Yb³⁺ inside the cell inhibited and delayed the rectifier potassium current I_K while the effect of inhibition also displayed upward tendency, La³⁺ and Gd³⁺ of 100μmol/L rarely influenced the activation of I_K while the activation of I_K shifted to the right because of Yb³⁺.

 

We translated the file about lanthanides from Chinese into English.

 

近年来, 镧系元素(lanthanides , Ln) 化合物的药用正在成为普遍关注的研究方向^{[ 1-4]}。除钆(gadolinium , Gd) 配合物在核磁诊断中广泛用作成像剂以外, 2004 年,碳酸镧作为治疗肾功能衰竭高磷酸血症的药物被FDA 批准上市(商品名Fosrenol ^R ) 。这些都提升了大家对稀土药用的期望。但是,也发现了它们的一些毒性表现^{[ 5-6]}。尤其是最近几年,因发现Gd 核磁成像剂所引起的严重毒性反应引起了大家对Ln 药用安全性问题的关注。比如，Gd 配合物有可能引起肾源性系统纤维化^[7]；2000 年, Briner 等根据动物实验结果提出镧具有行为致畸作用^[8]。2007年，Guliaev等提出La³⁺在脑损伤情况下会穿过血脑屏障对缺血神经元有保护作用^[9]。程驿等报道稀土使红细胞膜产生畴结构和“打洞”,增加膜通透性,使Ln 漏入细胞^[10]。由于镧系收缩,它们的离子半径从La³⁺ 到Lu³⁺ 依次降低。实际上,它们的生物效应常常表现显著差别。稀土元素作用外周神经系统的规律研究几乎没有，对于稀土化学性质的差别与生物效应的差别间的关系也缺少规律性的认识。所以我们从中选择La³⁺,Gd³⁺,Yb³⁺三种有代表性的稀土研究其对背根神经元的影响。

研究结果显示，10、100、1000 μmol/L LaCl₃和GdCl₃处理DRG神经元96 h，细胞凋亡率递增，但都不具有显著差异；三个浓度组YbCl₃处理96h，细胞的凋亡率递增，与对照组相比都具有显著差异。胞外100μmol/L的La³⁺,Gd³⁺,Yb³⁺抑制瞬间外向钾电流I_A，使I_A的激活和失活过程都显著右移，抑制和右移的程度是La³⁺最弱，Gd³⁺次之，Yb³⁺最强；胞内的La³⁺,Gd³⁺,Yb³⁺抑制延迟整流钾电流I_K，抑制的程度呈递进趋势，100μmol/L La³⁺和Gd³⁺基本不影响I_K的激活，Yb³⁺使I_K的激活右移。

 

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