维生素D，维生素K，雌二醇和睾酮对结石模型大鼠肾骨桥蛋白表达的影响

目的 :探讨骨桥蛋白的表达和调控与尿石症的关系。方法 :分别用维生素D、维生素K、雌二醇和睾酮处理正常大鼠和结石模型大鼠 ,连续用药 7d ,免疫组化和Northernblot技术检测大鼠肾骨桥蛋白及其mRNA的表达 ,偏光显微镜观察大鼠肾晶体沉积情况 ,并测定尿晶体成分的含量。结果 :维生素K、雌二醇和睾酮均可上调骨桥蛋白及其mRNA的表达 ,减少大鼠肾草酸钙晶体的沉积。维生素D增加尿钙的排泄量 ,促进晶体沉积。结论 :维生素K、雌二醇和睾酮可上调肾骨桥蛋白的表达 ,抑制结石的形成 ,维生素D过量则可促进结石形成     

维生素D和维生素K对结石大鼠肾脏骨桥蛋白mRNA表达的影响

目的：进一步明确维生素Ｄ 和维生素Ｋ 与肾结石的关系。方法：健康成年雄性ＳＤ大鼠３６ 只随机分成６组,即对照组、单纯成石组、维生素Ｄ组、诱石剂＋ 维生素Ｄ 组、维生素Ｋ 组和诱石剂＋ 维生素Ｋ组,测定肾脏骨桥蛋白（ｏｓｔｅｏｐｏｎｔｉｎ, ＯＰＮ） ｍＲＮＡ 的表达量和尿晶体成分的浓度。结果：维生素Ｄ 和维生素Ｋ 均可促进肾脏表达ＯＰＮ ｍＲＮＡ;维生素Ｄ可升高尿钙,维生素Ｋ则抑制尿草酸的分泌,诱石剂有降低尿镁和柠檬酸的作用。结论：维生素Ｄ过多可促进肾结石形成,而维生素Ｋ 有抑制结石形成的作用。     

泽泻活性成分对肾结石模型大鼠bikunin表达的影响

目的研究中药泽泻活性成分对结石模型大鼠肾结石形成和bikunin表达的影响,以探讨泽泻防治草酸钙尿石症的作用机理.方法分离提取泽泻的化学活性成分,制作大鼠肾草酸钙结石模型.将Wistar大鼠随机分成对照组、结石模型组、泽泻组,采用半定量逆转录聚合酶链反应检测大鼠肾组织bikunin mRNA的表达水平、镜下观察肾组织草酸钙晶体分布,同时检测大鼠血生化、肾钙含量、24h尿钙和尿草酸的分泌量.结果①泽泻组大鼠肾组织草酸钙晶体分布、血生化等指标均明显低于结石组.②泽泻组和成石组大鼠肾组织bikunin的相对表达水平分别为(0.528±0.170,0.713±0.250)、肾钙含量分别为[(4.70±0.08)mg/g,(9.49±0.45)mg/g]、24h尿钙分泌量分别为[(37.23±1.84)μmol,(61.49±2.06)μmol],各组间差异均有显著性意义(P＜0.05).结论泽泻活性成分能下调bikunin在结石大鼠肾组织的表达,减少肾组织草酸钙晶体的形成,从而抑制大鼠肾结石形成.     

泽泻活性成分对结石模型大鼠肾结石形成和bikunin表达的影响

目的 研究中药泽泻活性成分对结石模型大鼠肾结石形成和bikunin表达的影响,以探讨泽泻防治草酸钙尿石症的作用机理。方法 分离提取泽泻的化学活性成分,制作大鼠肾草酸钙结石模型。将30只Wistar大鼠随机分成对照组、结石模型组、泽泻组,每组10只大鼠。采用半定量逆转录聚合酶链反应检测大鼠肾组织bikunin mRNA的表达水平、镜下观察肾组织草酸钙晶体分布,同时检测大鼠血生化、肾钙含量、24 h尿钙和尿草酸的分泌量。结果(1)泽泻组大鼠肾组织草酸钙晶体分布、血生化等指标均明显低于结石组。(2)泽泻组和成石组大鼠肾组织bikunin的相对表达水平分别为0.53±0.17,0.71±0.25、肾钙含量分别为4.70 mg/g±0.08 mg/g,9.49 mg/g±0.45 mg/g、24 h尿钙分泌量分别为37μmol±2μmol,62μmol±2μmol,各组间差异均有显著意义(P<0.05)。结论 泽泻活性成分能下调bikunin在结石大鼠肾组织的表达,减少肾组织草酸钙晶体的形成,从而抑制大鼠肾结石形成。     

夏枯草提取物对肾草酸钙结石模型大鼠肾组织骨桥蛋白表达的影响

目的研究夏枯草50％甲醇提取物对大鼠肾组织骨桥蛋白（osteopontin，OPN）表达的影响。方法采用乙二醇和氯化铵诱导建立大鼠肾草酸钙结石模型，将24只Wistar大鼠随机分成3组：对照组（A）、结石组（B）、夏枯草组（C）。C组则通过灌胃方式予一定剂量的夏枯草50％甲醇提取物。饲养4周后，检测各组大鼠肾组织病理学改变和草酸钙结晶沉积情况。采用原位杂交RT—PCR观察各组大鼠肾组织中OPN mRNA表达，免疫组织化学和Westem blot检测各组大鼠肾组织OPN蛋白的表达水平。结果A组肾小管正常，B组肾小管腔可见大量成片草酸钙结晶存在，管腔明显扩张；C组肾小管腔可见少许散在草酸钙结晶存在，管腔轻度扩张。原位杂交显示A组大鼠肾组织中仅肾脏髓质小部分亨利氏袢中检测到OPN mRNA的表达，与此相反在B组和C组大鼠肾组织中则明显检测到OPN mRNA的表达，只是C组中OPN mRNA的表达强度相对弱于成石对照组。RT-PCR检测结果与原位杂交一致。免疫组化显示A组中仅能检测到OPN蛋白的微弱表达，B组大鼠肾组织中OPN表达则明显增强，C组大鼠肾组织中OPN表达强度低于B组。Western blotting检测显示A组轻度表达OPN，而B组则显著表达，C组表达强度低于B组。结论夏枯草50％甲醇提取物能有效抑制大鼠肾组织OPN的表达，减少肾组织草酸钙结晶的沉积，从而能有效抑制大鼠肾草酸钙结石的形成。     

女贞子对去卵巢大鼠钙代谢及维生素D依赖型基因表达的影响

目的研究补肾中药女贞子对去卵巢大鼠钙代谢及维生素D依赖型基因表达的影响。方法大鼠去卵巢手术处理4周后,ig给药治疗14周。血清、尿液及粪便中钙水平采用比色法测定。RT-PCR技术分析小肠及肾脏基因表达。结果大鼠去卵巢后体内钙流失显著增加,表现在血钙下降,尿钙及粪钙排泄增加。女贞子可以有效防止尿钙及粪钙排泄增加,并恢复血钙水平。RT-PCR分析表明雌二醇和女贞子都可以抑制去卵巢引起的小肠维生素D受体(VDR)mRNA表达下降。女贞子对肾脏25-羟基维生素D 1-羟化酶(1-OH ase)及25-羟基维生素D 24-羟化酶(24-OH ase)mRNA无明显作用,但却可以提高肾脏钙结合蛋白-9k(C aBP-9k)及钙结合蛋白-28 k(C aBP-28k)的基因表达。结论女贞子能够改善雌激素缺乏所引起的钙失衡状态,主要是通过提高小肠对活性维生素D的敏感性及加强肾脏对钙的重吸收而发挥作用的。     

夏枯草提取物抑制大鼠肾草酸钙结石形成作用的研究

目的 研究夏枯草提取物对大鼠肾草酸钙结石的作用及机制. 方法 将40只雄性Wistar大鼠随机分为4组:对照组、模型组、夏枯草提取物低剂量(50 g/L)和高剂量(100 g/L)实验组.实验4周后处死动物,将各组大鼠肾脏标本制成组织切片,H-E染色,观察大鼠肾组织病理学改变;检测大鼠血清尿素氮(BUN)、血清肌酐(Cr)、磷(P)和Ca2+的含量,检测24 h尿液中Ca2+和草酸(Ox)的含量;运用荧光定量PCR和Western-blot检测大鼠肾内TRPV5 mRNA和蛋白的表达,并进行统计学分析. 结果 与对照组比较,模型组大鼠肾呈现草酸钙结石病理改变,不同浓度的夏枯草提取物作用后,可明显改善其病理变化.模型组血清BUN,Cr,Ca2+和P含量明显升高,经不同浓度的夏枯草提取物作用后,实验组BUN及Cr含量明显低于模型组(P＜0.05),但实验组和模型组Ca2+及P含量比较无显著性差异;模型组尿液Ca2+,Ox含量较对照组明显升高,经不同浓度的夏枯草提取物作用后,可降低实验组Ca2+含量,且成药物剂量依赖性(P＜0.05),但对Ox的含量无显著性作用;模型组肾内TRPV5mRNA和蛋白的表达明显降低,经不同浓度的夏枯草水提取物作用后,实验组TRPV5 mRNA和蛋白的表达逆转,且具有统计学意义(P＜0.05). 结论 夏枯草对大鼠肾草酸钙结石具有防治作用;可能是通过上调大鼠肾脏尿钙调控信号TRPV5的表达,降低血清中BUN、Cr含量及尿液中Ca2+的含量.     

Decreased expression of vitamin K epoxide reductase complex subunit 1 in kidney of patients with calcium oxalate urolithiasis

Urinary prothrombin fragment 1 (UPTF1) is a potent inhibitor of urinary stone formation.UPTF1 exerts such inhibitory effect by effective γ-carboxylation in which vitamin K epoxide reductase complex sub...     

益肾通淋汤对尿石病人尿中草酸钙结晶的影响

本文就益肾通淋汤对尿结石病人尿中的草酸钙结晶的影响进行了随机对照观察。结果:实验组尿中出现草酸钙结晶、大晶体、结晶聚体的例数比对照组少(P<0.01)。提示益肾通淋汤有抑制尿石病人尿中草酸钙结晶的析出、增大和聚集的作用,以及可能有预防尿结石的形成和复发的作用。     

Decreased renal vitamin K-dependent γ-glutamyl carboxylase activity in calcium oxalate calculi patients

Objective To study the activity of vitamin K-dependent γ-glutamyl carboxylase in patients with calcium oxalate (CaOx) urolithiasis compared with healthy individuals and to assess its relationship to the renal calcium oxalate urolithiasis. Methods Renal parenchymas were harvested from urolithic patients and renal tumor patients undergoing nephrectomy. The renal carboxylase activity was evaluated as the radioactivity of ［14C］ labeled sodium bicarbonate in carboxylic reactions in vitro using β-liquid scintillation counting. Results Significantly reduced activity of renal vitamin K-dependent γ-glutamyl carboxylase was observed in the urolithic group as compared with normal controls (P&lt;0.01). Conclusion It suggests that the reduced carboxylase activity observed in the urolithic patients may play an important role in the course of renal calcium oxalate urolithiasis.     

A Comparative Study on Several Models of Experimental Renal Calcium Oxalate Stones Formation in Rats

In order to compare the effects of several experimental renal calcium oxalate stones formation models in rats and to find a simple and convenient model with significant effect of calcium oxalate crystals deposition in the kidney, several rat models of renal calcium oxalate stones formation were induced by some crystal-inducing drugs (CID) including ethylene glycol (EG), ammonium chloride (AC), vitamin D3 [1α(OH)VitD3, alfacalcidol], calcium gluconate, ammonium oxalate, gen-tamicin sulfate, L-hydroxyproline. The rats were fed with drugs given singly or unitedly. At the end of experiment, 24-h urines were collected and the serum creatinine (Cr), blood urea nitrogen (BUN), the extents of calcium oxalate crystal deposition in the renal tissue, urinary calcium and oxalate ex-cretion were measured. The serum Cr levels in the stone-forming groups were significantly higher than those in the control group except for the group EG L-hydroxyproline, group calcium gluconate and group oxalate. Blood BUN concentration was significantly higher in rats fed with CID than that in control group except for group EG L-hydroxyproline and group ammonium oxalate plus calcium gluconate. In the group of rats administered with EG plus Vitamin D3, the deposition of calcium ox-alate crystal in the renal tissue and urinary calcium excretion were significantly greater than other model groups. The effect of the model induced by EG plus AC was similar to that in the group in-duced by EG plus Vitamin D3. EG plus Vitamin D3 or EG plus AC could stably and significantly in-duced the rat model of renal calcium oxalate stones formation.     

四种类型尿结石与尿液成分的关系

目的探讨四种类型结石与24 h尿液成分之间的关系.方法体外震波碎石术(ESWL)后,取石放红外光谱分析,检测结石成分,确定结石类型;用生化方法检测结石成分.结果红外光谱分析四种类型结石:一水草酸钙,二水草酸钙,草酸钙 羟基磷灰石,尿酸.尿液成分分析与对照组比较,含荜酸钙的结石类型,尿总钙含量显著减少(P＜0.01),但一水荜酸钙与二水草酸钙结石患者尿量显著减少,而草酸钙 羟基磷灰石这种复合成分的结石患者pH值偏高(P＜0.05),尿枸橼酸含量显著偏低(P＜0.01),这二种成分变化有别于前者;尿酸结石中所有成分都显著减少(P＜0.01).尿酸结石与草酸钙 羟基磷灰石结石比较,除尿磷、尿枸橼酸无明显差异外,其他成分都有显著性差异.结论检测24 h尿液成分的变化对推断结石类型.指导临床治疗与预防有应用意义.     

Association of Vitamin D Receptor Gene Polymorphisms with Calcium Oxalate Calculus Disease

Urinary calculus is a common disease that isclosely related to the disorder of calcium metabolismand has the tendency of polygenic inheritance.Butup to now its predisposing genes have yetto be iden-tified.Vitamin D receptor(VDR) can regulate themetabolism of calcium and phosphorus in the body.Its allele polymorphisms are widely used to detectge-netic characteristics of some diseases such as osteo-porosis,rickets and secondary hyperparathy-roidism[1— 6 ] .In recent years,some researchers be-…     

银安淡泉水对肾结石形成影响的实验研究

目的 应用大白鼠草酸钙肾结石模型,研究淡泉水对肾结石形成的影响。方法 实验分自来水组、去离子水组和淡泉水组。对各组大鼠的肾脏外观、肾脏湿质量和干质量、肾结石形成情况及病理检查结果进行比较。结果 淡泉水对乙二醇和氯化胺诱发的大鼠肾结石模型有明显抑制作用。结论 初步认为多饮淡泉水对预防尿石症有一定意义,对尿石症术后防止复发亦有积极作用。     

Effect of trace elements on the kinetics of calcium oxalate crystallization—Research on urolithiatic inhibitors

Summary In order to find effective urolithiasis inhibiting factors, calcium oxalate stones were investigated by spectrum analysis. Of the composite trace elements nine were selected to test their effect on the kinetics of calcium oxalate crystallization in artificial and in urinary stone patient’s urine, and in experimental animals respectively. It was found that Mo and Sr could effectively inhibit calcium oxalate crystallization and decrease the renal total and crystalline calcium. The inhibitive effect of the trace elements, the mechanism of action, the required conditions and the way of their affecting the kinetics of calcium oxalate crystallization are discussed. Their clinical significance and the possibility of practical application are referred to.     

人钠/二羧基转运蛋白1在肾组织的表达变化及其与肾结石发病的关系

目的研究肾组织钠/二羧基转运蛋白1(hNaDC1)表达变化与肾结石发病的的关系.方法85例肾结石患者分为、尿枸橼酸正常结石组和低枸橼酸尿结石组.并设50例对照为非结石患者.采用RT-PCR及Northem印迹法检测其中部分肾结石患者肾组织的hNaDC1mRNA水平;免疫组化检测hNaDCl蛋白表达的变化;常规生化方法测定血、尿枸橼酸、草酸等生化指标.结果低枸橼酸尿结石组结石复发率(36.1%),显著高于尿枸橼酸正常结石组(16.3%,P＜0.01).hNaDC1mRNA在正常肾组织中有表达,分布于近端肾小管刷状缘;低枸橼酸尿结石患者hNaDC1mRNA/18sRNA比值(0.65±0.21)显著高于对照组(0.36±0.11,P＜0.01);而尿枸橼酸正常结石患者(0.4±0.13)与对照组比较差异无显著意义(P＞0.05);低枸橼酸尿结石组hNaDC1蛋白表达也显著高于对照组及尿枸橼酸正常结石组(P＜0.01),而后两组间差异无显著意义(P＞0.05).低枸橼酸尿结石组尿pH值、尿钠水平显著低于尿枸橼酸正常结石组和对照组;尿钙、尿草酸水平均显著高于对照组,与尿枸橼酸正常结石组无显著差异.结论肾组织hNaDC1表达上调可能是低枸橼酸尿的重要原因,与肾结石的形成和复发存在某种内在联系.     

草酸钙尿石症患者尿液和结石中凝血酶原片段检测及其意义

为比较正常人和尿石症患者尿液中凝血酶原片段1（UPTF1）在含量及其与草酸钙晶体的结合能力，以探讨UPTF1含量或功能异常与草酸结石形成的关系，用ELISA法检测正常人和尿石症患者24h尿液、用过饱和结晶法制备的晶体表面结合物质和结石基质中UPTF1的含量。结果发现尿石症患者尿液中能与草酸钙结合的UPTF1的浓度及其在24h尿中含量显著低于正常人组；UPTF1普遍存在于含钙结石中。结果表明：尿石症患者尿液中抑制结石形成的UPTF1明显减少可能是结石形成的重要原因。