苄丙酮香豆素对实验性大鼠肾草酸钙结石形成的影响

目的：探讨Vit．K拮抗剂苄丙酮香豆素(商品名华法令)对大鼠肾草酸钙结石形成的影响。方法：采用乙二醇饮水和氯化铵灌胃作成石剂，30只Wistar大鼠随机分为对照组(A组)、成石组(B组)、华法令组(C组)。饲养4周后，检测大鼠肾组织钙含量和草酸钙晶体形成、24h尿钙、尿草酸含量及血生化指标。结果：成石组和华法令组肾组织中钙、镁含量，24h尿草酸及尿钙、镁排泄量差异无显著性意义；镜下观察发现：华法令组大鼠肾脏草酸钙结晶形成多于成石组，但组间比较差异无显著性意义。结论：苄丙酮香豆素对大鼠肾草酸钙结石的形成无显著影响。     

4种大鼠肾草酸钙结石模型的比较

目的筛选简便、快捷、成石效果好的SD大鼠肾草酸钙结石的造模方法。方法分别采用目前普遍使用的2种大鼠肾草酸钙结石的模型复制方法和2种改良的造模方法进行造模,并设立空白对照组,造模结束后采集每组大鼠24h尿量及血清,比较大鼠24h尿量、尿Ca2＋、尿Mg2＋、尿pH、尿草酸（0x）及血尿素氮（BUN）、肌酐（cr）、P、Ca2＋、Mg2＋,肾脏病理切片HE染色后光学显微镜下观察和比较各组大鼠肾脏病理改变及草酸钙结晶的沉积情况。结果E组[1％乙二醇＋2％氯化铵＋10％葡萄糖（48d）]在光学显微镜下草酸钙结晶沉积较传统组C组明显增多（P〈0．05）,但有30％大鼠死亡,血肌酐在5组大鼠中最高。D组[1％乙二醇＋2％氯化铵＋10％葡萄糖（28d）]较传统组C组草酸钙结晶沉积明显增多（P〈0．05）,并且造模时间短,大鼠存活率高（80％）,E组与D组相比结晶形成量无统计学意义（P〉0．05）,B组[1％乙二醇（28d）3肾脏中无肾结晶形成,仅有轻微的肾脏病理学改变,大鼠无死亡,肌酐不高。空白对照组无结晶形成,无病理改变。结论用1％乙二醇＋2％氯化铵＋10％葡萄糖诱导28天复制肾草酸钙结石模型的效果好,并且花费时间短,大鼠存活率高,建议选用。     

肾结石大鼠肾组织bikunin mRNA的表达

目的 :研究bikunin在实验性肾草酸钙结石大鼠肾组织的表达及意义。方法 :采用乙二醇和氯化铵诱导大鼠肾草酸钙结石模型形成 ,检测各组大鼠肾功能、肾组织Ca2 + 含量和草酸钙晶体沉积、尿生化指标 ,并用逆转录聚合酶链反应 (RT PCR)检测bikuninmRNA在肾组织的表达情况。结果 :模型组大鼠的血清Cr、BUN、肾Ca2 + 含量、2 4h尿Ca2 + 、草酸 (Ox)分泌量和肾组织bikuninmRNA的表达均明显高于正常组 (P <0 .0 5 )。结论 :高草酸尿和草酸钙结晶的沉积能促使大鼠肾脏通过合成更多的bikunin来抑制大鼠肾组织草酸钙晶体的形成。     

鱼油抑制实验鼠草酸钙结晶形成

目的 了解鱼油在尿石形成中的作用。方法 ６０只大鼠随机分４组,饮用１％乙二醇（ＥＧ）水,同时喂饲不同剂量的鱼油。４周后检测各组大鼠肾功能、草酸钙结晶、２４小时尿钙和尿草酸。结果 加服鱼油组鼠肾积水、组织水肿减轻,肾组织内草酸钙结晶数及含钙量明显减少,２４小时尿钙排出减少;尿尿素氮、肌酐排出明显增加,而血中尿素氮、肌酐浓度显著低于成石组。结论 鱼油能抑制实验性高草酸尿症大鼠体内草酸钙结晶形成,减少尿     

月见草油抑制草酸钙结晶形成的实验研究

目的了解月见草油在草酸钙结石形成中的作用,为临床治疗提供新的方法与思路。方法雄性SD大鼠60只,随机分为4组,各组15只。C组和D组以月见草油（含γ-亚麻酸9.2%）或葵花籽油（含亚油酸70%）10g/kg灌胃4周后,用诱石剂1%乙二醇（EG）加2%氯化氨喂饮,同时继续以月见草油或葵花籽油灌胃4周,8周后检测各组大鼠肾功能、24h血尿生化指标和肾草酸钙结晶情况;仅饲普通饲料（A组,空白组）和普通饲料加1%乙二醇（EG）加2%氯化氨喂饮（B组,成石组）大鼠作为对照。结果月见草油组肾组织水肿较轻,肾内草酸钙结晶数及肾成石率低于成石组（P〈0.05）,尿枸橼酸较成石组高（P〈0.01）,24h尿钙、尿草酸排泄均低于成石组（P〈0.01）,血尿素氮（P〈0.01）、血肌酐（P〈0.05）低于成石组。结论γ-亚麻酸能有效改善肾功能,减少尿钙及草酸的排泄,抑制实验鼠肾草酸钙结晶形成,在尿石症防治方面可能有一定应用价值。     

金钱草及广金钱草对大鼠肾草酸钙结石相关代谢产物作用的研究

目的对比金钱草与广金钱草抑制大鼠肾草酸钙结石的具体机制与作用效果。方法54只SPF级SD雄性大鼠适应性喂养1周至体重180~200 g,使用乙二醇灌胃法建立SD大鼠肾草酸钙结石模型,而后将大鼠按照随机数字表法分为9组处理并进行对照,分别为健康对照组(A组),阳性对照组(建模组,B组),金钱草低、中、高剂量组(C1、C2、C3组,共3组),广金钱草低、中、高剂量组(D1、D2、D3组,共3组),疗效对照组(枸橼酸氢钾钠组,E组),每组各6只。4周后收集标本测定各组大鼠血尿生化指标,并行Von Kossa染色检测肾草酸钙晶体,在偏振光显微镜下观察大鼠肾组织草酸钙结晶沉积情况,利用测算照片中阳性面积百分比与相关血尿生化指标判断两者药效差异。计量资料以均数±标准差(x±s)表示,组间比较采用单因素方差分析,两组间比较采用SNK-q检验;结晶形成情况组间比较采用Kruskal-Wallis检验。结果与阳性对照组相比,高剂量的广金钱草相对金钱草能显著降低肾草酸钙结石大鼠血肌酐水平,应用金钱草后血肌酐水平为(86.70±11.49)μmol/L,应用广金钱草后血肌酐水平为(70.72±9.08)μmol/L,两者差异有统计学意义(P<0.01);高剂量金钱草、广金钱草均能显著升高尿镁水平,降低血尿素水平,两者相比差异无统计学意义(P>0.05);与阳性对照组相比,给予高剂量金钱草(P<0.0001)与高剂量广金钱草(P<0.0001)均能显著抑制大鼠肾草酸钙晶体形成,保护大鼠肾脏,两者作用效果相比差异无统计学意义(P>0.05);给予金钱草与广金钱草均未能观察到显著升高尿pH值与显著降低尿钙、尿草酸、24 h尿量、血钙、血磷、血镁、血尿酸和肾草酸含量的效果。结论广金钱草抑制大鼠肾草酸钙结石发生的功效优于金钱草,对肾功能具有更好的保护作用。     

草酸钙结石形成的代谢性变化的研究

目的分析顺德勒流地区草酸钙结石患者的血生化及尿液代谢变化,探讨草酸钙结石形成的代谢性因素,为临床提供诊治的依据。方法对确诊为草酸钙结石的患者进行病例对照研究,并进行尿pH值、24h尿定量分析及血生化检测。结果 （1）85例草酸钙结石患者中出现低尿量者71例,高钠尿症38例,高钙尿症53例,高尿酸尿症15例,低枸橼酸尿症74例,高草酸尿症42例,高磷尿症3例,高pH值尿28例,而28例高pH值尿患者合并低枸橼酸尿症者25例;（2）草酸钙组与对照组的24h尿定量分析结果显示,草酸钙结石组尿量、尿枸橼酸均显著低于对照组（均P〈0.005）,而尿pH值、尿钠、尿钙及尿草酸明显高于对照组（均P〈0.005）,其他指标无显著统计学差异;（3）草酸钙组与对照组血生化指标比较,血钙、血钠浓度明显高于对照组,其他指标无统计学差异（均P〈0.005）。结论低尿量、低枸橼酸尿症、高钠尿症、高钙尿症、高草酸尿症、高血钙及高血钠是顺德勒流地区草酸钙结石形成的重要代谢因素。     

三种维生素对大白鼠草酸钙肾结石形成的影响

成熟雄性大鼠５５只，分成４组，乙二醇法诱导肾结石的形成。实验组大鼠分别补充大剂量维 生素Ｂ６、维生素Ｃ、维生素Ｄ，用１５Ｃａ示踪测定肾结石。并测定各组大鼠２４ 小时尿钙、镁、草酸、磷、尿 量。结果显示，维生素Ｂ６组肾脏放射性强度显著降低（Ｐ＜０．０５），但尿草酸排泄无明显变化；维生素Ｃ对肾草酸钙沉积和尿草酸、磷、镁和钙的排泄无明显影响，但有明显利尿作用（Ｐ＜０．０５）；大剂量维生素Ｄ能明显促进肾结石的形成（Ｐ＜０．０１）。     

雌激素抑制肾草酸钙结石形成机制的研究进展

肾结石多为草酸钙结石,为外科常见病,发病率逐年升高。近年来,研究发现雌激素与草酸钙结石之间关系密切。众所周知,男性肾结石的患病率普遍高于女性。多项研究表明,雌激素缺乏的女性更易患有肾结石,有更高的尿草酸及尿钙排泄量。雌激素作为草酸钙结石的抑制剂,其在多种与草酸钙结石形成相关的机制中发挥关键作用,如促进骨桥蛋白(osteopontin,OPN)表达、抑制氧化应激和促进尿柠檬酸盐排泄等。雌激素替代治疗可显著减少草酸钙晶体沉积。本文将对雌激素与肾草酸钙结石之间的关系进行综述。     

草酸钙尿石患者VKDC结构域基因突变的研究

泌尿系结石以草酸钙结石最为常见。现已发现尿液中存在一些大分子蛋白质与尿石形成相关，越来越多的研究证实尿凝血酶原片段1（UPTF1）是正常人尿草酸钙结晶的主要抑制因子之一。     

Calcium-sensing receptor promotes calcium oxalate crystal adhesion and renal injury in Wistar rats by promoting ROS production and subsequent regulation of PS ectropion,OPN, KIM-1, and ERK expression

ObjectivesTo explore the mechanism of calcium-sensing receptors (CaSRs) during the development of nephrolithiasis.Materials and methodsWistar rats were treated with ethylene glycol to induce calcium oxalate crystallization, and gadolinium chloride (GdCl₃, an agonist of CaSR) and NPS 2390 (an antagonist of CaSR) were added. Oxidative stress (OS) and calcium oxalate crystals in the kidney were observed. CaSR expression and the expression of extracellular signal-regulated protein kinase (ERK), OPN, and KIM-1 were determined by western blotting. In addition, renal tubular epithelial cells were isolated from the kidney to observe phosphatidylserine (PS) ectropion using flow cytometric analysis. Various biochemical parameters were assessed in serum and urine at the end of the experiment.ResultsCalcium oxalate increased OS, crystal adhesion, PS ectropion, and the expression of CaSR and ERK, OPN, and KIM-1 in vivo. In addition, lower levels of urine citrate as well as increased serum creatinine and urea levels were observed after treatment with calcium oxalate (p < .05). Compared with calcium oxalate treatment alone, the above deleterious changes were further significantly confirmed by GdCl₃ but were reversed by NPS-2390. However, urine calcium excretion was decreased after ethylene glycol treatment but was significantly reduced by NPS 2390 and increased by GdCl₃ (p < .05).ConclusionsThe results suggest that CaSR might play significant roles in the induction of nephrolithiasis in rats by regulating reactive oxygen species (ROS) and PS ectropion and the composition of urine, OPN, KIM-1, and ERK expression.     

Uninephrectomy enhances urolithiasis in ethylene glycol treated rats.

Uninephrectomy (uNX) usually induces compensatory hyperfunction of the remaining kidney in an attempt to preserve the homeostasis of body fluid composition. The present study used uninephrectomized Sprague-Dawley rats on a lithogenic diet (0.5% ethylene glycol, EG) to evaluate the influence on urinary stone formation and calcium oxalate crystal deposition of compensatory excretion of lithogenic substances in the remnant kidney. The results showed that there were no urinary stones or calcium oxalate crystal deposits in the intact or uNX rats fed a normal diet. In the EG feeding groups, the incidence of massive (grade 3) crystal deposits was significantly higher in the uNX rats (87.5%) than that in the intact rats (37.5%; P less than 0.05). The incidence of urinary stone formation was also higher in the uNX rats as compared to that of the intact rats, although the difference did not achieve statistical significance. The serum magnesium, phosphorus and creatinine increased significantly, whereas creatinine clearance (CCr), 24-hour urinary excretions of citrate, sodium, potassium and chloride decreased significantly in the uNX rats fed EG. These data indicate that uninephrectomy increases the vulnerability of the contralateral remnant kidney to urolithiasis and crystal deposition when the lithogenic risk factors are present. Furthermore, once the remnant kidney forms urolithiasis or massive calcium oxalate crystal deposits, the renal function is severely compromised.     

筛选乙二醇法复制大鼠肾结石模型最佳剂量的比较研究

目的：探讨乙二醇法复制大鼠肾结石模型的最佳剂量，建立乙二醇法复制规范化大鼠肾结石模型的方法。方法：采用不同浓度的乙二醇（1％、1．25％、1．5％、2％）分别与1％氯化铵溶液制作大鼠肾结石模型，实验用药第4周处死大鼠，用7150全自动生化仪测定血与尿Ca^2＋、Mg^2＋、P^3＋、UA含量，用变色酸比色法测定肾组织中草酸含量；无菌取肾组织，常规石蜡包埋、组织切片、比染色、偏光显微镜观察肾组织病理改变及大鼠肾成石情况。结果：在不同浓度的乙二醇4个剂量组中，血与尿Ca^2＋、Mg^2＋、P^3＋、UA，肾组织中草酸含量以及肾成石情况不以乙二醇浓度而增加，以1．25％乙二醇合1％氯化铵对大鼠肾成石作用为优。结论：1．25％乙二醇合1％氯化铵是复制肾结石模型的最佳剂量组，可以作为乙二醇法复制的规范化的大鼠肾结石模型。     

大鼠肾草酸钙结石模型制备效果的比较研究

目的 验证大鼠肾草酸钙结石模型制备方法,为癸壬化石丸治疗肾结石的药理作用及机制研究选择有效的大鼠肾草酸钙结石模型.方法 按文献报道的四种大鼠肾草酸钙结石模型制备方法,将SD大鼠分为A、B、C、D四组,A组采用1％乙二醇+2％氯化铵溶液进行灌胃,B组采用1％乙二醇+2％氯化铵+10％葡萄糖进行灌胃,C组采用1％乙二醇+10％葡萄糖酸钙进行灌胃,D组采用1％乙二醇+2％氯化铵+10％葡萄糖酸钙进行灌胃,28 d后检查尿常规、尿生化、血生化和肾脏标本的病理切片后比较肾草酸钙结石模型制备效果.结果 四种方法制备大鼠肾草酸钙结石模型,造模效果D组＞A组＞B组＞C组.结论 采用1％乙二醇+2％氯化铵+10％葡萄糖酸钙所形成大鼠肾草酸钙结石模型效果较好.     

Prevention of renal crystal deposition by an extract of <Emphasis Type="Italic">Ammi visnaga</Emphasis> L. and its constituents khellin and visnagin in hyperoxaluric rats

In Egypt, teas prepared from the fruits of Ammi visnaga L. (syn. “Khella”) are traditionally used by patients with urolithiasis. The aim of this study was to evaluate whether oral administration of an aqueous extract prepared from the fruits of A. visnaga as well as two major constituents khellin and visnagin could prevent crystal deposition in stone-forming rats. Hyperoxaluria was induced in male Sprague-Dawley rats by giving 0.75% ethylene glycol and 1% ammonium chloride via the drinking water. The Khella extract (KE; 125, 250 or 500 mg/kg) was orally administered for 14 days. The histopathological examination of the kidneys revealed that KE significantly reduced the incidence of calcium oxalate (CaOx) crystal deposition. In addition, KE significantly increased urinary excretion of citrate along with a decrease of oxalate excretion. Comparable to the extract, khellin and visnagin significantly reduced the incidence of CaOx deposition in the kidneys. However, both compounds did not affect urinary citrate or oxalate excretion indicating a mechanism of action that differs from that of the extract. For KE, a reasonably good correlation was observed between the incidence of crystal deposition, the increase in citrate excretion and urine pH suggesting a mechanisms that may interfere with citrate reabsorption. In conclusion, our data suggest that KE and its compounds, khellin and visnagin, may be beneficial in the management of kidney stone disease caused by hyperoxaluria but that it is likely that different mechanism of action are involved in mediating these effects.     

Studies on the in vitro and in vivo antiurolithic activity of Holarrhena antidysenterica

Holarrhena antidysenterica has a traditional use in the treatment of urolithiasis, therefore, its crude extract has been investigated for possible antiurolithic effect. The crude aqueous-methanolic extract of Holarrhena antidysenterica (Ha.Cr) was studied using the in vitro and in vivo methods. In the in vitro experiments, Ha.Cr demonstrated a concentration-dependent (0.25–4?mg/ml) inhibitory effect on the slope of aggregation. It decreased the size of crystals and transformed the calcium oxalate monohydrate (COM) to calcium oxalate dehydrate (COD) crystals, in calcium oxalate metastable solutions. It also showed concentration-dependent antioxidant effect against 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals and lipid peroxidation induced in rat kidney tissue homogenate. Ha.Cr (0.3?mg/ml) reduced (p?<?0.05) the cell toxicity and LDH release in renal epithelial cells (MDCK) exposed to oxalate (0.5?mM) and COM (66?μg/cm²) crystals. In male Wistar rats, receiving 0.75?% ethylene glycol (EG) for 21?days along with 1?% ammonium chloride (AC) in drinking water, Ha.Cr treatment (30–100?mg/kg) prevented the toxic changes caused by lithogenic agents; EG and AC, like loss of body weight, polyurea, oxaluria, raised serum urea and creatinine levels and crystal deposition in kidneys compared to their respective controls. These data indicate that Holarrhena antidysenterica possesses antiurolithic activity, possibly mediated through the inhibition of CaOx crystal aggregation, antioxidant and renal epithelial cell protective activities and may provide base for designing future studies to establish its efficacy and safety for clinical use.     

The influence of sex hormones on renal osteopontin expression and urinary constituents in experimental urolithiasis

PURPOSE: To our knowledge the influence of sex hormones on urinary stone formation remains undetermined. We investigated the effect of castration on urinary lithogenic factors and renal osteopontin expression in rats previously treated with ethylene glycol. MATERIALS AND METHODS: Sprague-Dawley rats were divided normal males, castrated males, males with 2 weeks of 0.75% ethylene glycol treatment, castrated males with 2 weeks of 0.75% ethylene glycol treatment, normal females, castrated females, females with 2 weeks of 0.75% ethylene glycol treatment and castrated females with 2 weeks of 0.75% ethylene glycol treatment. We analyzed 24-hour urine samples for urinary constituents, such as calcium, oxalate, citrate, uric acid, phosphate, magnesium, sodium, potassium and creatinine. The kidneys were examined for osteopontin expression by Northern blot analysis and for crystal deposition by histological examination. RESULTS: In intact male rats calcium and citrate excretion decreased and oxalate excretion increased significantly after ethylene glycol treatment. Castrated male rats with ethylene glycol had greater calcium and less oxalate excretion than male intact rats with ethylene glycol. In intact female rats uric acid excretion decreased and only calcium excretion increased significantly after ethylene glycol treatment. Castrated female rats with ethylene glycol excreted significantly more oxalate and less calcium than intact female rats with ethylene glycol. Renal osteopontin expression was the same in male intact and castrated rats, and in female intact and castrated rats. In males with ethylene glycol expression was stronger in castrated than in intact rats. In females with ethylene glycol expression was weaker in castrated than in intact rats. No crystal deposits were found in the kidneys in any group. CONCLUSIONS: Testosterone appears to promote stone formation by suppressing osteopontin expression in the kidneys and increasing urinary oxalate excretion. Estrogen appears to inhibit stone formation by increasing osteopontin expression in the kidneys and decreasing urinary oxalate excretion.