Simulation of calcium oxalate stone <Emphasis Type="Italic">in vitro</Emphasis>

Crystallization of calcium oxalate is studied mainly in the diluted healthy urine using scanning electron microscopy (SEM), and is compared with the crystallization in the diluted pathological urine. It suggests that the average sizes of calcium oxalate crystals are not in direct proportion to the concentrations of Ca²⁺ and Ox^2- ions. Only in the concentration range of 0.60-0.90 mmol/L can larger size of CaOx crystals appear. When the concentrations of Ca²⁺ and Ox^2- ions are 1.20, 0.80, 0.60, 0.30 and 0.15 mmol/L in the healthy urine, the average sizes of calcium oxalate crystallites are 9.5 X 6.5, 20.0 X 13.5 and 15.0 jj,m X 10.0 jj,m, respectively, for the former three samples after 6 d crystallization. No crystal appears even after 30 d crystallization for the samples of concentrations of 0.30 and 0.15 mmol/L due to their low supersaturations. The results theoretically explain why the probability of stone forming is clinically not in direct proportion to the concentrations of Ca²⁺ and Ox^2- ions. Laser scattering technology also confirms this point. The reason why healthy human has no risk of urinary stone but stone-formers have is that there are more urinary macromolecules in healthy human urines than that in stone-forming urines. These macromolecules may control the transformation in CaOx crystal structure from monohydrate cal-cium oxalate (COM) to dihydrate calcium oxalate (COD). COD has a weaker affinity for renal tubule cell membranes than COM. No remarkable effect of the crystallization time is observed on the crystal morphology of CaOx. All the crystals are obtuse hexagon. However, the sizes and the number of CaOx crystals can be affected by the crystallization time. In the early stage of crystalli-zation (1-6 d), the sizes of CaOx crystals increase and the number of crystal particles changes little as increasing the crystallization time due to growth control. In the middle and late stages (6-30 d), the number of crystals increases markedly while the growth rate changes little due to the nucleation control.     

二水草酸钙的形成及其对尿路结石的防治

二水草酸钙(COD)是泌尿系结石的主要成分之一,其成核、生长和聚集过程与尿石的形成密切相关。本文结合我们近年来的工作,综述了生物膜及其模拟膜对COD的调控作用,尿大分子、焦磷酸盐、多磷酸盐、柠檬酸、酒石酸及表面活性剂等尿小分子的诱导作用,过饱和度、化学计量条件、pH值、离子强度、温度等体系参数对COD形成的影响;讨论了COD的形貌、晶面电荷及其与细胞膜粘附的研究进展。从临床上预防和治疗草酸钙结石的角度,综述了有利于COD形成的因素。     

粘液素对草酸钙晶体生长的影响

泌尿系结石是一种常见疾病。在70％以上的结石中,草酸钙(CaOxa)单独或和其它钙盐共同为主要成分。一般认为正常人不形成尿石是其尿液中存在的抑制剂抑制了CaOxa晶体的成核、生长、聚集或固相转化。     

Circular patterns of calcium oxalate crystals induced by defective Langmuir-Blodgett film

The injury of the renal epithelial cell membrane can promote the nucleation of nascent crystals, as well as adhesion of crystals on it. It thus accelerates the formation of renal calculi. In this paper, the defective Langmuir-Blodgett (LB) films were used as a model system to simulate the injured renal epithelial cell membrane. The microcosmic structure of the defective LB film and the molecular mechanism of the effect of this film on nucleation, growth, deposited patterns and adhesion of calcium oxalate monohydrate (COM) were investigated. The circular defective domains were formed in dipalmitoylphosphatidylcholine (DPPC) LB film after the film was treated by potassium oxalate. These domains could induce ring-shaped patterns of COM crystals. In comparison, the LB film without pretreatment by potassium oxalate only induced random growth of hexagonal COM crystals. As the crystallization time increased, the size of COM crystals in the patterns increased, the crystal patterns changed from empty circles to solid circles, and the number of the circular patterns with small size (5-20 μm) increased. The results would shed light on the molecular mechanism of urolithiasis induced by injury of the renal epithelial membrane at the molecular and supramolecular level.     

凝胶体系中羧酸对草酸钙结晶的影响

羧酸是泌尿系结石形成的抑制剂。本文采用双扩散法考察凝胶体系中一元羧酸HAc、二元羧酸酒石酸、三元羧酸柠檬酸和四元羧酸EDTA对草酸钙(CaOx)结晶的影响。HAc没有抑制作用。酒石酸和柠檬酸能够改变一水草酸钙(COM)晶体的形貌，并抑制草酸钙晶体二维生长，这种抑制作用随时间的增加而增强。EDTA使COM晶体在长度方向生长更快，而在宽度和厚度上生长更慢。随着结晶温度的降低，形成草酸钙晶体的时间增加，且二水草酸钙(COD)的比例增加。在5℃的低温条件下，添加有二元、三元和四元羧酸的CaOx结晶中，COD成为主要的物相。     

枸橼酸盐抑制泌尿系结石形成的化学基础

本文综述了防石药物枸橼酸及其盐对泌尿系结石形成、抑制和治疗的化学基础，重点讨论了其与钙离子的配位、封闭尿石矿物生长活性位点、抑制草酸钙的成核和生长、增加尿液中尿大分子和枸橼酸浓度、改变尿液pH以及诱导二水草酸钙和三水草酸钙形成，并讨论了抗衡阳离子对枸橼酸盐抑制能力的影响。     

Effect of Concentration of Structurally-Different Carboxylic Acids on Growth and Aggregation of Calcium Oxalate in Gel Systems

The effect of concentration of structurally-different carboxylic acids such as ethylene diamine tetraacetic acid （H4edta）, citric acid （H3cit）, tartaric acid （H2tart）, and acetic acid （HOAc） on growth and aggregation of calcium oxalate （CaOxa） in gel systems was comparatively investigated. H2tart and H3cit could change the morphology of cal- cium oxalate monohydrate （COM） and induce the formation of calcium oxalate dihydrate （COD）. H4edta could induce the formation of COD at a lower concentration of 0.33 mmol/L and have the strongest ability to inhibit aggregation of COM. HOAc inhibited COM aggregation only at a higher concentration than 500 mmol/L. With increasing the number of carboxylic groups in an acid or increasing the concentration of carboxylic acid, the capacity of this acid to induce COD formation and to inhibit growth and aggregation of COM crystals increased. That is, this capacity followed the order： H4edta〉H3cit〉H2tart〉 〉HOAc. The result in this work suggested that the presence of H3cit and H2tart in urine played a role in the natural defense against stone formation.     

Effects of temperature and sodium carboxylate additives on mineralization of calcium oxalate in silica gel systems

Urolithiasis remains a major medical problem in China, especially in Guangdong Province in the southest of China[1]. A survey in Shenzhen city, the most southern city in China, showed the incidence of renal calculus was 4.87%, being 6.12% in the males and 4.07% in the females[2]. The prevalence of renal calculus has been more as the age advances and in the male population and so was in the less-educated population. The recurrence rate is more than 80%, with a moderate improvement by conventi…     

脂质体中不同种类羧酸钾对草酸钙晶体生长的调控作用

首次研究了狼磷脂-水脂质体中不同种类羧酯钾对草酸钙晶体生长的调控作用 。加入一元DAc只诱导一水草酸钙（COM）生成。二元K_2tart在其浓度大于1. 0mmol/L时可以诱导三水草酸钙（COT）生成。而加入三元的K_3cit和四元的 K_2edta后， 在不同的浓度下，可以分别诱导COM，二水草酸钙（COD）和COT的生 成。在低浓度（—3.3-17mmol/L）范围，， COD含量达到100%；而在较高浓度(＞ 17mmol/L)时，COD减少，COT含量增加。在不同的浓度区间，无论是COM含量减少， 还是COT含量增加，或者是COD含量的先增加后减少，均与该羧酸钾浓度的对数呈线 性关系。不同羧酯钾抑制COM生长并诱导COD形成的能力顺序为：K_3cit＞K_2edta ＞＞K_2tart-KAC,诱导COT生长的能力顺序为：K_2tart＞＞K_3cit＞K_2edta＞＞ KAc.由此推测抑制草酸钙结石形成的潜在效率依次为：K_3cit＞K_2edta＞＞ K_2tart＞＞KAc.     

二维琼脂凝胶体系中过渡金属离子对草酸钙晶体生长和周期性沉淀的影响

在二维凝胶圆盘体系中,研究过渡金属离子对草酸钙晶体生长和周期性环状沉淀的影响,并对其形成机理进行探讨.结果表明:在一定浓度的Fe3 存在下,体系中出现了周期性环状沉淀现象.同时发现在此条件下抑制了一水合草酸钙(COM)晶型生成.此外,加入Zn2 、Co2 、Ni2 体系中的晶体都以二水合草酸钙(COD)为主;而加Cu2 离子的圆盘中,三水合草酸钙(COT)占据了主要的成分,这说明不同的过渡金属离子对三种草酸钙晶型的生成影响不同.另外,还对出现的与尿结石有关的特殊现象(白斑和放射状的条纹)进行了探讨.     

海藻硫酸多糖抑制草酸钙结石形成的化学模拟

用体外模拟方法研究了从海藻异枝麒麟菜中提取的硫酸多糖(ESPS)对尿结石患者尿液中草酸钙晶体生长的影响. ESPS不但诱导与尿路细胞膜粘附力较弱的二水草酸钙晶体形成, 而且抑制一水草酸钙的生长和聚集, 归因于一水草酸钙的富钙(101)晶面与聚阴离子ESPS之间的静电相互作用. 上述结果表明, ESPS是一种抑制草酸钙结石的潜在绿色药物.     

不同结构的磷酸盐对凝胶体系中草酸钙晶体物相和相组成的影响

泌尿系结石的形成是一种病理性生物矿化过程，不同地区的结石发病率在3％～15％之间。且50％(美国)至80％(中国)的人会复发。结石中约70％以上为草酸钙(CaC2O4)结石。CaC2O4结石的形成与其热力学(过饱和度)和动力学(成核、生长和聚集)因素有关。由于结石患者尿液和正常人尿液中     

肾小管上皮细胞损伤及其诱导草酸钙晶体成核

肾上皮细胞损伤可促进肾结石形成.本文采用过氧化氢(H2O2)对人类肾小管上皮细胞(HKC)进行了氧化损伤,采用扫描电子显微镜(SEM)、X射线衍射分析(XRD)和倒置显微镜观察了HKC损伤前后的形态变化及其调控草酸钙(CaOxa)晶体成核、生长的差异;采用zeta电位分析仪检测了损伤前后HKC表面的zeta电位变化.结果表明,H2O2能明显地损伤HKC,降低细胞活性,且在H2O2浓度范围0.1～0.5mmol/L、作用时间0.5～1.5h内具有明显的剂量和时间的依赖性;使用0.5mmol/LH2O2作用1.5h可使HKC损伤达到饱和状态.HKC损伤程度增加后,其诱导的晶体数量显著增加,但晶体尺寸增加不明显(P0.05),表明损伤细胞诱导尿石症形成主要是增加晶体的成核位点而非促进晶体的生长.本文所建立的HKC氧化损伤的模型有助于进一步阐明CaOxa结石形成的细胞机制.     

土家族药物天葵化石汤提取液抑制草酸钙结石形成的化学模拟

采用扫描电子显微镜(SEM)和X射线衍射法(XRD)研究了土家族药物天葵化石汤(Tiankui)的提取液对尿石晶体草酸钙(CaOxa)成核、生长的抑制作用及其对二水草酸钙(COD)的稳定作用. 当Tiankui浓度小于30 mg/mL时, 主要生成一水草酸钙(COM), 但可使COM晶体棱角圆钝. 随着Tiankui浓度增加至45和75 mg/mL, 可分别诱导95%和100%的COD晶体生成. Tiankui还可以稳定COD在水溶液中的存在, 没有Tiankui存在时, COD在48 h内全部转化为COM晶体, 而在12 mg/mL Tiankui存在下, COD仅有20%转化. 从Tiankui提取液的活性组分、与草酸钙不同晶相间的吸附差异、化学配位等角度讨论了其抑制CaOxa生长和诱导稳定COD的化学基础.     

大豆多糖对尿石矿物草酸钙形成的调控作用

采用水提法从大豆中提取了大豆多糖(SPS),其多糖百分含量为97.38%;平均相对分子质量为115,200,羧基百分含量为13.8%。采用X射线衍射法(XRD)、红外光谱(FTIR)、扫描电子显微镜(SEM)和电感耦合等离子体发射光谱仪(ICP)研究了水溶性大豆多糖(SPS)对草酸钙晶体生长的调控作用。SPS大豆多糖不但可以抑制一水草酸钙(COM)晶体的聚集,而且可以诱导二水草酸钙(COD)晶体形成。当SPS浓度由0增大到0.50g·L-1时,草酸钙晶体由COM完全转变为COD晶体;并且随着多糖浓度的增大,溶解在溶液中的钙离子(可溶性钙)浓度显著增加,草酸钙沉淀的物质的量逐渐减少。这些结果表明,SPS有望成为预防草酸钙结石的一种绿色药物。     

Electrophoretic behaviour of calcium oxalate monohydrate in liquid mixtures

An experimental investigation on electrophoresis of calcium oxalate monohydrate in several liquid mixtures (methanol-, ethanol-, 2-propanol-, and methanol-acetonewater) is described.The electrophoretic transport is considered from the view-point of the Thermodynamics of Irreversible Processes. Linear relations have always been found between the mass flux and the applied electric field. The -potential of the interface C.O.M./liquid mixture has been estimated by using the classial theory of electrophoretic mobility of colloidal particles. The influence of the composition of the mixture on the electrophoretic coefficient has been discussed on the basis of the variation of -potential, viscosity and dielectric constant with the molar fraction of alcohol for binary mixtures and acetone for ternary mixtures. The concentration dependence of the electrophoretic coefficient is found to be linear only in the latter case.     

硅凝胶体系中不同结构羧酸钾对草酸钙结晶的影响

采用扫描电子显微镜(SEM)和X射线衍射(XRD)方法研究了硅凝胶体系中不同种类羧酸钾对草酸钙(CaC₂O₄)晶体生长的调控作用. 加入一元醋酸钾(KOAc)只生成一水草酸钙(COM)晶体; 三元柠檬酸钾(K₃Cit)和四元乙二胺四乙酸二钾(K₂EDTA)可诱导二水草酸钙(COD)形成, 且随着其浓度增加, 对COD的诱导能力增加, 而二元酒石酸钾(K₂Tart)同时诱导了COM, COD和三水草酸钙(COT)生成. 随着结晶温度降低, 多元酸钾可以进一步减小COM晶体的比表面积, 增加COD的百分含量, 但K₂Tart诱导COT的能力减弱. 由于诱导COD和COT晶体形成、减小COM的比表面积均有利于防止草酸钙尿石的形成, 因此, 多元羧酸钾可用于草酸钙结石的预防和治疗.     

The Effect of Potassium Citrate on Simultaneous Growth of Calcium Oxalate Mono-, Di-, and Trihydrate in Synthetic Urine

Kidney stone disease, which occurs in about 10% of the U.S. population, causes substantial suffering and occasional renal failure, yet the disease mechanism is poorly understood1. Kidney stones mostly contain microcrystals of calcium oxalate monohydrate (…     

Inhibition of the Crystal Growth and Aggregation of Calcium Oxalate by Algae Sulfated Polysaccharide In-vitro

Kidney stone disease causes substantial suffering and occasional renal failure. The content of calcium oxalate (CaOxa) is up to 70-80% in the stones1,2. However, the mechanism of the formation of urinary stones is not yet clearly understood and the questi…     

肾上皮细胞损伤对草酸钙形成和黏附的影响

肾结石是病理性生物矿化的产物,其主要矿物为草酸钙。肾小管上皮细胞(REC)损伤在肾结石形成过程中起着关键作用。本文综述了REC损伤后膜表面表达的功能分子,特别是可促进晶体黏附的含酸性基团分子,包括磷脂酰丝氨酸、透明质酸、如骨桥蛋白、跨膜糖蛋白等;从分子和超分子水平上讨论了这些功能分子调控草酸钙成核、生长和黏附的机理及其影响因素;并提出了今后的研究方向。