多沙唑嗪治疗下段输尿管结石

为评估多沙唑嗪在下段输尿管结石中诱导自然排石方面的疗效，并比较多沙唑嗪对于不同大小结石的作用，Liatsikos等人进行了一项研究[J Endourol，2007，21（5）：538-541]。研究入选73例年龄46．3岁的有下段输尿管结石的患者，根据结石大小和治疗方法将平均分为4组：A组15例患者结石〈5mm，不采用多沙唑嗪治疗；B组16例患者结石直径5-10mm；C组20例患者结石直径〈5mm，多沙唑嗪4mg／d连续治疗4周；D组22例患者结石直径5-10mm，多沙唑嗪4mg／d连续治疗4周。A组、B组分别为C组、D组的对照组。结果显示A组中有9例患者（60％）有自然排石，C组中17例患者有自然排石（85％）（P=0．047）；     

邻苯二甲酸二丁酯致尿道下裂大鼠发育异常和阴茎病理学改变研究

目的邻苯二甲酸二丁酯（DBP）孕晚期染毒诱导子代雄鼠尿道下裂发生和探讨DBP致尿道下裂雄鼠发育异常和阴茎病理学改变。方法雌鼠怀孕14～18d，每天分别灌胃给予大豆油（A组），DBP500（B组）、800（C组）、1200（D组）mg／kg体重，分娩后统计仔鼠数和雄仔鼠体重。出生后（PND）7d测量雄仔鼠肛门生殖器距离（AGD），观察尿道下裂发生率和尿道下裂阴茎病理学改变。PND70,对尿道下裂雄仔鼠称重后解剖，评价发育情况。结果C组仔鼠数和雄仔鼠体重明显减少；D组出现孕鼠死亡和零产仔；尿道下裂仅C组发生。发生率为36．5％。PND7，B、C组雄仔鼠AGD和A组相比明显减小。阴茎连续性病理切片显示典型尿道下裂改变。解剖得尿道下裂雄仔鼠肝、肾、前列腺、睾丸、附睾脏器系数与A组相比明显减小，脑垂体脏器系数明显增大。结论800mg／kg体重DBP孕晚期染毒能高诱导雄仔鼠尿道下裂发生，DBP不仅损害雄仔鼠生殖系统，还引起发育异常。     

坦索罗辛联合甲基泼尼松龙治疗输尿管下段结石的临床研究

目的：评价坦索罗辛与甲基泼尼松龙联合应用治疗输尿管下段结石的作用。方法：选取120例输尿管下段结石（0．4～1．0cm）患者,随机分为3组。A组为对照组,给予常规治疗;B组在A组治疗方案基础上加坦索罗辛0．4mg,1次／d;C组在B组基础上加甲基泼尼松龙8mg,2次／d。均观察期为2周,统计结石排出率、结石排出时间、使用止痛剂的例数。结果：A组排出结石者为19例,B组为31例,C组为38例,B、C组排石率高于A组（P〈0．05）,C组排石率高于B组（P〈0．05）;平均排石时间分别为（9．3±3．5）d,（5．1±2．8）d和（4．9±2．4）d,B、C组短于A组（P〈0．05）;出现肾绞痛而给予哌替啶者分别为10例,2例,1例,B、C组少于A组（P〈0．05）。治疗期间未出现明显副作用。结论：坦索罗辛和甲基泼尼松龙联合治疗可提高输尿管下段结石排石率,缩短排石时间,减少止疼药的用量。     

维生素D3和维生素K3对实验性肾结石的影响

目的：探讨维生素C3和维生素K3与尿石症的关系。方法SD大鼠36只,随机分为对照组（A组）、成石组（B组）、维生D3组（C组）、成石＋维生素D3组（D组）、维生素K3组（E组）和成石＋维生素K3组（F组）,用免疫组化和原位杂交技术检测各组大鼠肾脏骨桥蛋白（OPN）及其mRNA的表达量,并测定尿晶体成分的浓度。结果：免疫组化结果显示,OPN主要表达于肾脏远曲小管和集合管,B、C、E组鼠肾和OPN的表达强度明显高于A组（P均＜0．05）;D、F组OPN的表达强度明显高于C、E组（P均＜0．05）,即维生素D3或维生素K3与诱石剂合用时呈相加效应。应用诱石剂后,D组尿钙排泄量明显增加,而F组草酸盐明显低于B组（P＜0．05）。维生素K3可减少尿划石剂后,D组尿排泄量明显增加,而组草酸盐明显低于B组（P＜0．05）。维生素K3可减少尿草酸盐的分泌和草酸钙晶体的沉积。结论：维生素D3可能通过多种机制种促进肾结石殂成,而维生素K3有抑制结石形成的作用。     

丙酮酸乙酯对重症急性胰腺炎大鼠肠黏膜HMGB1表达的影响

目的探讨丙酮酸乙酯（EP）对大鼠重症急性胰腺炎（SAP）肠组织中高迁移率族蛋白B1（HMGBl）表达的影响，以期为SAP的治疗提供思路。方法雄性Wistar大鼠90只随机分为3组：A组为SAP组；B组为SAP＋EP处理组（EP组）；C组假手术对照组（对照组）。3组动物于术后3，6，12，24，48h取材。测定血淀粉酶（AMY）、D-乳酸、肠组织丙二醛（MDA）含量。通过光学显微镜观察肠组织病理变化及免疫组织化学法观察HMGBl在肠组织中的表达。Western-blot法进行HMGBl检测。结果A，B组AMY和D-乳酸水平明显升高，但B组较A组显著降低（P〈0．05）。A组肠组织中MDA明显高于C组（P〈0．01），B组肠组织中MDA升高幅度较A组小（P〈0．05）。B组较A组肠组织病理损伤明显减轻。A组6h时肠组织HMGBl表达水平显著高于C组，于24h达峰值，且持续至48h（P〈0、01）。B组肠组织HMGBl表达水平均明显低于A组（P〈0．05）。结论SAP时，HMGBl可介导肠黏膜通透性增加。EP能显著抑制HMGBl的表达，改善肠黏膜屏障功能，对SAP肠黏膜损伤有明显的保护作用。     

不同后路短节段内固定术治疗Hangman 骨折的生物力学比较

目的：测试不同后路短节段内固定术治疗Hangman骨折的生物力学性能，探讨内固定方式的选择。方法：8具新鲜C0～C4颈椎标本，按照①正常状态（对照组）；②Ⅰ型骨折C2椎弓根螺钉固定（A组）；③ⅡA型骨折C2椎弓根螺钉固定（B组）；④Ⅱ型骨折C2椎弓根螺钉固定（C组）；⑤Ⅲ型骨折C2椎弓根螺钉固定（D组）；⑥Ⅲ型骨折C2、3椎弓根侧块钢板内固定（E组）顺序在脊柱三维运动实验机上依次测试其三维运动范围（ROM），对结果进行统计学分析。结果：A组ROM值与对照组无显著性差异；B组除旋转外与对照组无显著性差异，旋转稳定性也达到了对照组的61．86％；C组与对照组均有显著性差异；D组ROM值最大，与对照组有显著性差异；E组除后伸外ROM值均明显小于对照组，差异有显著性（P〈0．05）。结论：C2椎弓根螺钉固定可使Ⅰ型Hangman骨折达到生理性固定，使ⅡA型骨折恢复较好的稳定性，不能使Ⅱ、Ⅲ型骨折获得稳定；后路C2、3椎弓根侧块钢板内固定后的三维稳定性较好，适合不稳定型Hangman骨折的外科治疗。     

组织间植入125I粒子诱导H22肝肿瘤细胞凋亡的研究

目的观察^125I粒子近距离照射对H22肝癌细胞凋亡的影响及其机制。方法用原位末端脱氧核苷酸转移酶标记法（TUNEL）检测^125I粒子近距离照射对H22细胞凋亡的影响；免疫组化Elivion^TM plus法检测Survivin蛋白的表达。60只小鼠分为A组：植入放射性粒子；B组：植入化疗药DDP；C组：植入放射性粒子和化疗药DDP；D组：正常对照组。结果^125I粒子近距离照射和／或化疗后对H22肝癌肿瘤体积抑制率A、B、C组分别为43．8％、40．7％和58．3％；凋亡指数（AI）分别为（25．15±10．36）、（33．42±12．25）和（42．34±13．95），与对照组D组（20．45±14．54）比较，C组其凋亡指数（AI）差异有统计学意义（P〈0．05）；Survivin蛋白的表达率分别为50．0％、55．6％和36．4％，与D组100．0％比较，C组表达率差异有统计学意义（P〈0．05）。结论^125I粒子近距离照射H22肝癌可有效诱导肝癌细胞凋亡，抑制肝癌细胞增殖；联合化疗药，其凋亡作用更强；Survivin可能参与了其中的调节作用。     

组织工程神经修复大鼠坐骨神经缺损的研究

目的观察组织工程神经修复SD大鼠1．5cm长坐骨神经缺损的效果。方法用甘油处理10只SD大鼠2．0cm长坐骨神经，制备成同种异体脱细胞基质，备用。取SD乳鼠10只，分离坐骨神经，去神经外膜后，剪成小碎块，在DMEM中培养3周，扩增后的细胞鉴定、备用。3个月龄的SD雌性大鼠40只，单纯随机分成4个神经移植组（A、B、C、D），每组10只。A组：用扩增的雪旺细胞加同种异体脱细胞基质桥接，即组织工程化人工神经组。B组：用元雪旺细胞但具有内部支架结构的同种异体脱细胞基质桥接。C组：自体神经移植组。D组；空白对照组。术后12周，进行一般情况、小腿三头肌湿重、再生神经的组织学观察。结果完成对40只大鼠（每组10只）的实验评估。所有大鼠伤口瑚愈合，元死亡。A、B、C组大鼠足部元溃疡形成，D组7只足部有溃疡形成，所有组实验侧小腿三头肌较健侧萎缩，但以D组最明显。小腿三头肌湿重、神经电生理监测A组、C组差异无统计学意义（P〉O．05），A、C组与B、D组差异有统计学意义（P〈O．05），B组与D组差异有统计学意义（P〈0．05）。A组和C组的胫前肌中均能诱发出波幅明显的神经肌肉复合动作电位（CMAP），B组、D组中则仅录到波幅很低的CMAP。A组和C组再生轴突已通过移植段神经全长，远端肌肉轻度萎缩。B组部分通过移植段神经；D组不能通过移植段神经，6例形成神经瘤。结论组织工程人工神经可用来修复大鼠长段神经缺损。     

肺表面活性物质对胎粪吸入鼠肺功能的影响

目的：探讨外源性肺表面活性物质（PS）对胎粪吸入鼠肺功能的影响。方法：28只Wistar大白鼠进行人工通气，经气道注入3－4ml/kg胎粪溶液，PaO2降至20kPa以下后将动物随机分为4组（每组7只）。A组，气道内注入PS 150mg/kg(50mg/ml,3ml/kg)；B组，气道内注入等量生理盐水；C组，用PS稀溶液75mg/kg(5mg/ml,15ml/kg)进行支气管肺泡灌洗，重复2次；D组，用15ml/kg的生理盐水灌洗双肺。治疗后15min,30min,60min,120min,180min采血进行血气分析。180min后测定各组潮气量，并进行支气管肺泡灌洗（BAL），检测BAL液中总蛋白（TP）和TNF－α含量。结果：治疗后A和C组PaO2均明显升高，而B和D组在治疗后几乎不变，A、C组与B、D组相比，P＜0．05。A与C组间差异均无显著性。A和C组的潮气量明显高于B和D组（P＜0．05）。A和C组的BAL液中TP含量明显低于B和D组（P＜0．05）。TNF－α含量各组间无差异。结论：补充PS明显改善胎粪吸入鼠肺的氧合和顺应性。PS稀溶液灌洗法优于气道注入法。     

24h尿代谢评估在尿石症患者诊治中的意义

目的：比较同期住院的尿石症患者与非结石患者血生化、尿生化及尿a1微球蛋白（al—MG）、p2微球蛋白（82-MG）有无差异，并探讨其意义。方法：对比尿石症组66例（男45例，女21例），非结石（对照）组34例（男22例，女12例）统一生化仪器测定空腹血液生化及24h尿生化，放免法测定a1-MG及p2-MG含量。结果：两组间年龄、性别比差异无统计学意义。尿石症组血肌酐、尿素氮水平高于对照组，差异有统计学意义。尿石症组和对照组尿电解质水平差异无统计学意义，尿石症组尿a1-MG和p2-MG的含量高于对照组，微球蛋白差异有统计学意义。尿石症多尿组尿Ca、P水平高于尿石症少尿组及对照组，差异有统计学意义。结论：尿石症患者进行一次完备的24h代谢评估是必要的，尿a1-MG、p2-MG可能在泌尿系结石的发病中起一定作用。     

Testosterone Enhances whereas Estrogen Inhibits Calcium Oxalate Stone Formation in Ethylene Glycol Treated Rats

Purpose

The present study was conducted to extend our earlier study on the role of testosterone in the pathogenesis of urolithiasis and to further investigate the influence of sex hormone on the pathogenesis of calcium oxalate stone.

Materials and Methods

Adult Sprague-Dawley rats were divided into 9 groups, each containing 10 rats. Two groups of rats were left untreated and served as male and female controls. Another 7 groups of rats were fed a 0.5 percent ethylene glycol (EG) lithogenic diet for 4 weeks. Among them, 2 groups were male and female rats, 2 groups were castrated, 2 groups were castrated and then were subcutaneously implanted with testosterone, and 1 group of intact female rats was also subcutaneously implanted with testosterone. The stone and crystal deposits were examined by infrared spectrometer and polarizing and scanning electron microscope, respectively. Serum testosterone, creatinine and electrolytes and the renal excretion of oxalate, citrate and creatinine were determined.

Results

Subcutaneous implantation of exogenous testosterone restored calcium oxalate stone formation in castrated, EG-treated male rats (80 percent) and enhanced urolithiasis in castrated female rats receiving EG (40 percent). However, the testosterone effect was less striking in intact female rats fed EG (10 percent).

Conclusions

These data suggest that testosterone can promote and estrogen may inhibit calcium oxalate stone formation in EG-treated rats.     

Determinant role of testosterone in the pathogenesis of urolithiasis in rats.

By using an ethylene glycol-induced urolithiasis model, we assessed the role of testosterone in the pathogenesis of urolithiasis. The intact and castrated male and female rats were fed with 0.5% ethylene glycol in drinking water for four weeks. The renal excretions of oxalate, citrate and other electrolytes were measured, and the stone and crystal deposit were examined microscopically. The results showed that drinking a loading of 0.5% ethylene glycol for four weeks produced hyperoxaluria in all rats, but the intact male rats excreted more urinary oxalate than any other groups of rats. The ethylene glycol-fed rats exhibited hypocitraturia except the castrated male rats. However, urolithiasis occurred in intact male but not female rats. Castration in male rats fed with ethylene glycol dramatically decreased the incidence of renal stone from 71.4% (5/7) to 14.3% (1/7). On the other hand, there was still no renal stone formed in the oophorectomized female rats which received ethylene glycol treatment. These data indicate that serum testosterone level plays a determinant role in urolithiasis formation.     

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.     

Effect of castration and finasteride on urinary oxalate excretion in male rats

We investigated the effects of castration and finasteride administration on urinary oxalate (Ox) excretion in a rat ethylene glycol (EG) model of urolithiasis. Male adult SD rats were divided into six groups. Group 1 were normal, untreated rats. The other five groups, all treated with 0.75% EG for 4 weeks; were as follows: group 2, non-castrated (intact) rats; group 3, castrated rats; group 4, castrated rats with a 4-cm testosterone implant; group 5, intact rats treated with high-dose finasteride (7.5 mg%); and group 6, intact rats treated with low-dose finasteride (0.75 mg%). Urinary Ox excretion increased 12.8-fold after 4 weeks of EG treatment (group 2 vs group 1). Both castration (group 3) and finasteride administration (groups 5 and 6) significantly decreased urinary Ox excretion compared with intact rats (group 2). We conclude that dihydrotestosterone is partially responsible for the exaggerated hyperoxaluria observed in the rat EG model of urolithiasis. Received: 2 July 1997 / Accepted: 19 September 1997     

性激素对男性原发性上尿路结石的影响

目的：探讨性激素特别是雄激素对男性原发性上尿路结石形成的影响，方法：检测并比较36例男性原发性上尿路结石患者和20例健康男性的血清睾酮（Testo)，促卵泡成熟激素（FSH），促黄体生成激素（LH），雌二醇（E2），催乳素（PRL），黄本酮（Prog)水平，结果：男性结石组Testo明显高于健康对照组（P＜0．01），其余5项无明显差别，结论：雄性激素对男性原发性上尿路结石的形成有一定影响。     

A traditional Chinese herbal antilithic formula,Wulingsan, effectively prevents the renal deposition of calcium oxalate crystal in ethylene glycol-fed rats

We investigated the effects of a traditional Chinese herbal formula, Wulingsan (WLS), on renal stone prevention using an ethylene glycol-induced nephrocalcinosis rat model. Forty-one male Sprague-Dawley (SD) rats were divided into four groups. Group 1 (n = 8) was the normal control; group 2 (n = 11) served as the placebo group, and received a gastric gavage of starch and 0.75% ethylene glycol (EG) as a stone inducer; group 3 received EG and a low dose of WLS (375 mg/kg); and group 4 received EG and a high dose of WLS (1,125 mg/kg). Baseline and final 24 h urine samples were collected individually; biochemical data of urine and serum were also obtained at the beginning and at the end of the experiment. After 4 weeks, animals were killed and kidneys were harvested. The kidney specimens were examined by polarized light microscopy and the crystal deposits were evaluated by a semi-quantitative scoring method using computer software (ImageScoring). The results revealed that the rats of placebo group gained the least significant body weight; in contrast, the rats of WLS-fed groups could effectively reverse it. The placebo group exhibited lower levels of free calcium (p = 0.059) and significantly lower serum phosphorus (p = 0.015) in urine than WLS-fed rats. Histological findings of kidneys revealed tubular destruction, damage and inflammatory reactions in the EG-water rats. The crystal deposit scores dropped significantly in the WLS groups, from 1.40 to 0.46 in the low-dose group and from 1.40 to 0.45 in the high-dose group. Overall, WLS effectively inhibited the deposition of calcium oxalate (CaOx) crystal and lowered the incidence of stones in rats (p = 0.035). In conclusion, WLS significantly reduced the severity of calcium oxalate crystal deposits in rat kidneys, indicating that Wulingsan may be an effective antilithic herbal formula.     

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。     

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.     

Calcium oxalate crystal localization and osteopontin immunostaining in genetic hypercalciuric stone-forming rats

BACKGROUND: The inbred genetic hypercalciuric stone-forming (GHS) rats develop calcium phosphate (apatite) stones when fed a normal 1.2% calcium diet. The addition of 1% hydroxyproline to this diet does not alter the type of stone formed, while rats fed this diet with 3% hydroxyproline form mixed apatite and calcium oxalate stones and those with 5% hydroxyproline added form only calcium oxalate stones. The present study was designed to determine the localization of stone formation and if this solid phase resulted in pathologic changes to the kidneys. METHODS: GHS rats were fed 15 g of the standard diet or the diet supplemented with 1%, 3%, or 5% hydroxyproline for 18 weeks. A separate group of Sprague-Dawley rats (the parental strain of the GHS rats), fed the standard diet for a similar duration, served as an additional control. At 18 weeks, all kidneys were perfusion-fixed for structural analysis, detection of crystal deposits using the Yasue silver substitution method, and osteopontin immunostaining. RESULTS: There were no crystal deposits found in the kidneys of Sprague-Dawley rats. Crystal deposits were found in the kidneys of all GHS rats and this Yasue-stained material was detected only in the urinary space. No crystal deposits were noted within the cortical or medullary segments of the nephron and there was no evidence for tubular damage in any group. The only pathologic changes occurred in 3% and 5% hydroxyproline groups with the 5% group showing the most severe changes. In these rats, which form only calcium oxalate stones, focal sites along the urothelial lining of the papilla and fornix of the urinary space demonstrated a proliferative response characterized by increased density of urothelial cells that surrounded the crystal deposits. At the fornix, some crystals were lodged within the interstitium, deep to the proliferative urothelium. There was increased osteopontin immunostaining in the proliferating urothelium. CONCLUSION: Thus in the GHS rat, the initial stone formation occurred solely in the urinary space. Tubular damage was not observed with either apatite or calcium oxalate stones. The apatite stones do not appear to cause any pathological change while those rats forming calcium oxalate stones have a proliferative response of the urothelium, with increased osteopontin immunostaining, around the crystal deposits in the fornix.     

Inhibitory effects of female sex hormones on urinary stone formation in rats.

BACKGROUND: The effects of female sex hormones on urinary stone formation are not known. This study was conducted to investigate the effects of these hormones on stone formation by using an ethylene glycol (EG) and vitamin D-induced rat urolithiasis model. METHODS: Adult female Wistar rats were fed the same diet for four weeks and were then divided into four groups (N = 10 each). One group was administered 0.5 ml of olive oil three times per week for four weeks as a control. The other three groups were administered 0. 5 microg of vitamin D3 and 0.5 ml of 5% EG three times per week for four weeks. The rats in two of these three groups were oophorectomized, and the rats of the remaining group underwent a sham operation on the day before the start of the four-week treatment period. One of the two oophorectomized groups was then administered a supplementation of female sex hormones (0.1 mg of estrogen and 2.5 mg of progesterone 3 times per week for 4 weeks). On the first day of the fifth week of the experimental period, the degree of crystal deposition was determined histologically, and the calcium content in renal tissue was measured. We also investigated the level of osteopontin (OPN) mRNA in renal tissues by Northern blot analysis. OPN is a matrix protein thought to be a promoter of stone formation. RESULTS: The urinary oxalate excretion, crystal deposition and calcium content in renal tissue and the expression of OPN-mRNA were greater in the oophorectomized rats compared with the controls, and the same parameters were inhibited by the female sex hormone supplementation. CONCLUSIONS: These results suggest that female sex hormones can inhibit renal crystal deposition in EG-treated rats by suppressing the urinary oxalate excretion and the expression of OPN.