结石病人尿骨桥蛋白测定的临床意义

目的　探讨骨桥蛋白 (OPN)与肾结石的关系。　方法　对 2 2例结石病人和 12例正常人尿骨桥蛋白及晶体成分的浓度进行检测。　结果　正常组、结石组手术前后尿骨桥蛋白的相对浓度分别为 2 9.30、2 6 .17和 10 .84。正常组尿镁和柠檬酸浓度分别为 3.86mmol/L和 1.42mmol/L ,结石组分别为 1.14mmol/L和 0 .33mmol/L ,组间差别有显著性意义 (P <0 .0 5 )。　结论　尿骨桥蛋白等抑制物分泌减少是尿石症发病的主要因素之一。     

Effects of citrate on renal stone formation and osteopontin expression in a rat urolithiasis model

Previous studies have described the inhibitory effects of citrate on calcium oxalate crystallization in place of crystal growth, but the effects of citrate on matrix proteins of stones has not been studied in vivo. To examine the effect of citrate on the matrix, we investigated the effect of citrate on osteopontin (OPN) expression, which we had previously identified as an important stone matrix protein. Control rats were treated with saline while rats of the stone group were treated with ethylene glycol (EG) and vitamin D₃, and the citrate groups (low-dose and high-dose groups) were treated with a citrate reagent compound of sodium citrate and potassium citrate, in addition to EG and vitamin D₃. The rate of renal stone formation was lower in the citrate groups than in the stone group. This was associated with a low expression of OPN mRNA in citrate-treated rats relative to that in the stone group. Citrate was effective in preventing calcium oxalate stone formation and reduced OPN expression in rats. Our results suggest that citrate prevents renal stone formation by acting against not only the crystal aggregation and growth of calcium oxalate but also OPN expression. Received: 7 June 2000 / Accepted: 20 September 2000     

Effects of allopurinol on renal stone formation and osteopontin expression in a rat urolithiasis model

BACKGROUND: The inhibitory effect of allopurinol on calcium oxalate urolithiasis has been reported, but its effect on stone matrix proteins has not been studied in vivo. To clarify the effect of allopurinol on the matrix, we investigated its effect on the expression of osteopontin (OPN), which we previously identified as an important stone matrix protein. METHODS: Control rats were not treated. Rats of the stone group were given ethylene glycol (EG) and vitamin D(3), while the allopurinol groups (low-dose group and high-dose group) were treated with allopurinol in addition to receiving EG and vitamin D(3). RESULTS: The rate of renal stone formation was lower in the allopurinol groups than in the stone group. This was associated with a low expression of OPN mRNA in allopurinol-treated rats relative to that in the stone group. CONCLUSION: Allopurinol was effective in preventing calcium oxalate stone formation and reduced OPN expression in rats. Our results suggest that allopurinol prevents renal stone formation by acting against not only the control of oxalate but also OPN expression.     

The effect of takusha, a kampo medicine, on renal stone formation and osteopontin expression in a rat urolithiasis model

Kampo medicine is a traditional Japanese therapeutic system which originated in China and was used to treat various diseases for hundreds of years. Kampo medicine had been also used for the cure and the prevention of urinary calculi for many years, but the effect and the mechanism of this use of kampo medicine are unclear. We examined the inhibitory effect of the kampo medicine takusha on the formation of calcium oxalate renal stones induced by ethylene glycol (EG) and vitamin D₃ in rats. We also investigated the effect of takusha on osteopontin (OPN) expression, which we previously identified as an important stone matrix protein. The control group rats were non-treated; the stone group rats were administered EG and vitamin D₃, and the takusha group was administered takusha in addition to EG and vitamin D₃. The rate of renal stone formation was lower in the takusha group than in the stone group; thus, the OPN expression in the takusha group was smaller than in the stone group. Takusha was effective in preventing oxalate calculi formation and OPN expression in rats. These findings suggest that takusha prevents stone formation including not only calcium oxalate aggregation but also proliferation. Received: 14 May 1998 / Accepted: 14 August 1998     

The effect of sex hormones on the incidence of experimental urinary bladder tumors in rats (author's transl)]

A study was conducted of the effects of testosterone propionate, estradiol and estriol on experimental bladder tumors induced in 8-week old Wistar-Imamichi strain male rats by oral administration of 0.02 mg/head/day of N-butyl-N-(4-hydroxybutyl)-nitrosamine as carcinogen for 8 weeks. In the group of rats which was not treated for 12 weeks after completion of the carcinogen administration, 6 of 25 cases showed bladder tumors and 2 of 25 showed hyperplasia. In the group of rats which was injected intramuscularly 3 mg/kg (body weight) of testosterone priopionate 1 time weekly from the beginning of carcinogen administration through the 20th week, 9 of 20 cases showed bladder tumors and 2 were with hyperplasia. In the group of rats which was injected intramuscularly 3 mg/kg (body weight) of estradiol 1 time weekly from the beginning of the carcinogen administration through the 20th week, 2 of 23 cases developed bladder tumors and 5 were with hyperplasia. (Author's, modified)     

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.     

α-亚麻酸对草酸钙结石鼠前列腺素E2的影响

目的：探讨前列腺素E2在尿结石形成中的作用以及α-亚麻酸对前列腺素E2的抑制作用。方法：将60只雄性Wistar成年大鼠随机分成空白对照组、成石组、苏子油组、葵花籽油组。所有大鼠适应性喂养1周后，空白对照组随后7周均饮用自来水。成石组前4周饮用自来水，后3周饮用诱石剂水，每日自来水2g／只灌胃1次。苏子油组7周内每日以苏子油2g／只灌胃1次，饮水同成石组。葵花油组7周内每日以葵花油2g／只灌胃1次，饮水同B组。8周后检测大鼠24h尿总钙、尿总镁、尿草酸、肌酐和各组大鼠尿前列腺素E2水平。结果：空白对照组和苏子油组尿总钙明显低于成石组。尿总镁、尿草酸对照组明显低于成石组，苏子油组、葵花籽油组、成石组之间则差异无显著性意义。尿肌酐对照组、苏子油组、葵花油组显著低于成石组。24h尿前腺素E2水平苏子油组、对照组显著低于成石组。葵花籽油组与成石组比较差异无显著性意义。成石组、苏子油组、葵花籽油组前列腺素E2水平与尿总钙含量成正相关性。结论：前列腺素E2可能参与并促进了尿结石的形成，α-亚麻酸可能通过抑制肾前列腺素E2的产生而抑制尿结石形成。     

The influence of age and sex on bone resorption of secondary hyperparathyroidism in renal osteodystrophy

Summary The severity and incidence of subperiosteal and intracortical bone resorption were evaluated from fine-detail hand radiographs at × 8 magnification in relation to age and sex in 239 chronically dialyzed adult renal failure patients. The severity of subperiosteal resorption decreased significantly with advancing age in both sexes and the incidence decreased somewhat more in males than in females; no such trends were apparent for intracortical resorption. Although the mean values for the grades of subperiosteal and intracortical resorption were significantly higher in females than in males, when the effect of age and duration of follow-up were taken into consideration, this sex difference remained significant only for intracortical resorption. It is concluded that when studying certain aspects of renal osteodystrophy, differences due to age, sex, and duration of follow-up should be considered in the final interpretation of data.     

The mechanical strength of the growth plate under the influence of sex hormones

As sex hormones are considered to play a role in the etiology of the slipped upper femoral epiphysis, the influence of sex hormones on the mechanical strength of the epiphyseal plate was investigated in 310 female and 70 male rats. Ovariectomy weakened the strength of the growth plate while orchiectomy strengthened it. Estrogen given after ovariectomy, markedly strengthened the plate. Histologic examination revealed that the width of the growth plate was narrower in the mechanically stronger group. Hydroxyproline content increased and hexosamine content decreased in the epiphyseal plates of the mechanically stronger group. These observations confirm the view that sex hormones, especially estrogen, regulate the mechanical, morphologic, and biochemical functions of the growth plate.     

The influence of sex steroid hormones on plasma calcitonin response to the calcium clamp in normal subjects

The influence of sex steroid hormones on plasma calcitonin levels in healthy subjects was studied in 15 males and 10 premenopausal (PREMF) and 12 postmenopausal females (PMF). A standardized ionized calcium stimulus was achieved by means of the calcium clamp technique, and a sensitive RIA was used to determine immunoreactive CT (iCT) in plasma. Plasma iCT levels increased in response to the calcium clamp with an initial peak at 15 or 30 min. The iCT levels then declined but remained at an elevated level for the rest of the 180-min infusion period in all three groups. In males a positive correlation was found between the serum testosterone levels at 0 min and the estimates for initial iCT response, i.e., the change between 0 and 15 min (r = 0.80, n = 11, p less than 0.01), between 0 and 30 min (r = 0.56, n = 15, p less than 0.05) and between 0 and the maximum value (r = 0.68, n = 15, p less than 0.01). In the two female groups no such correlation was found. Serum 17 beta-estradiol or dehydroepiandrosterone sulfate concentrations were not correlated either to basal iCT levels or to the iCT response to the calcium clamp. PMF had lower levels of 17 beta-estradiol than PREMF (p less than 0.001), while the testosterone levels were similar. The iCT levels and response to the calcium clamp showed no significant difference in the two groups. The results indicate that sex difference in the plasma CT levels may be related to different testosterone levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

护骨胶囊对去卵巢大鼠钙相关激素和性腺激素影响的研究

目的观察护骨胶囊(Hugu capsules,HG)对去卵巢大鼠血清中与钙代谢直接相关的激素和性激素及子宫的影响。方法将60只SD雌性大鼠随机分为假手术组(Sham)、去卵巢组(OVX)、仙灵骨葆胶囊组(Pos)和护骨胶囊低、中、高剂量组(HG-L、HG-M和HG-H)。大鼠卵巢切除后,隔天开始,连续灌胃3个月。处死大鼠,取大鼠子宫与血清,观察HG对子宫重量,血清1,25双羟维生素D3(1,25(OH)2D3)、甲状旁腺激素(PTH)、雌二醇(E2)、孕酮(P)、睾酮(T)变化及子宫内膜组织的影响。结果与Sham组比:OVX组的PTH(P0.01)和T(P0.05)升高,E2(P0.01)和P(P0.05)降低;子宫重量显著减少,子宫内膜萎缩。与OVX组比:PTH在HG各个剂量组都降低,在Pos组无变化;E2在HG-L和HG-M组显著增加,在Pos组无变化;P在HG-L组降低,在Pos组显著升高;T在HG-L和HG-H组无变化,HG-M组降低,而Pos组显著升高;HG各个剂量组和Pos组的子宫重量和子宫内膜较OVX组均无明显差异。结论护骨胶囊对OVX大鼠的作用是调节PTH和E2水平,此调节作用与仙灵骨葆胶囊的作用机制不一样。护骨胶囊在补充雌激素的同时对子宫的影响不大,为推广护骨胶囊临床防治绝经后骨质疏松提供了实验依据。     

Long-term treatment with ramipril attenuates renal osteopontin expression in diabetic rats

BACKGROUND: Osteopontin (OPN) mediates progressive renal injury in various renal diseases by attracting macrophages, and its expression is regulated by the renin-angiotensin system (RAS). We studied the association between OPN expression and tubulointerstitial injury, and investigated the effect of ramipril on OPN expression in an animal model of non-insulin-dependent diabetes mellitus (NIDDM): Otsuka Long-Evans Tokushima Fatty (OLETF) rats. METHODS: Control (Long-Evans Tokushima Otsuka, LETO) and diabetic (OLETF) rats were treated with ramipril (3 mg/kg in drinking water) or vehicle for nine months, starting at 20 weeks of age. Systolic blood pressure, body weight, urinary protein excretion and oral glucose tolerance tests (OGTT) were monitored periodically. Renal function, histology (glomerulosclerosis, tubulointerstitial fibrosis, and ED-1-positive cells as a measure of macrophage infiltration), and expressions of OPN and transforming growth factor-beta1 (TGF-beta1) were evaluated at the end of the study. RESULTS: Compared with the LETO rats, OLETF rats showed declines in creatinine clearance rate, increases in urinary protein excretion and systolic blood pressure, and development of glomerulosclerosis, tubulointerstitial fibrosis, and inflammatory cell infiltration (all P < 0.05). Blocking angiotensin II with ramipril significantly improved all of these parameters (all P < 0.01). At the molecular level, expressions of OPN and TGF-beta1 were up-regulated in the OLETF rats, and were markedly suppressed following ramipril treatment. The sites of strong OPN mRNA and protein expressions were localized to areas of renal injury. Of note, the expression of OPN mRNA was strongly correlated with the number of ED-1-positive cells (r = 0.560, P = 0.01) and the tubulointerstitial fibrosis score (r = 0.500, P < 0.05). CONCLUSIONS: Up-regulation of OPN expression may play a role in tubulointerstitial injury associated with diabetic nephropathy, and blockade of the RAS by ramipril may confer renoprotection by decreasing OPN expression in non-insulin-dependent diabetic nephropathy.     

Studies of urinary risk factors in urolithiasis

Urinary excretions of calcium, oxalate and uric acid were estimated in 160 stone-formers (male 118, female 42) and 257 healthy controls (male 207, female 50). Stone-formers were divided into two groups according to their stone analysis: calcium containing stone-formers and non-calcium stone-formers. Calcium stone-formers were divided again into those who had a single stone episode and multiple or recurrent stone episodes. Urinary calcium and oxalate showed significant increases in calcium stone-formers, while urinary uric acid increased only in male calcium stone-formers. Recurrent calcium stone-formers demonstrated significant high levels of urinary calcium excretion especially in males, whereas no difference of urinary oxalate excretion between recurrent and single stone-formers. The frequency distributions on the excretion of three subjects were estimated respectively in patients with calcium stone and in controls. Relative risks, risk curves and stone probabilities were proposed and compared. The higher excretion values of urinary calcium and oxalate closely related to higher risks of forming calcium stones. On the other hand, urinary uric acid did not have such a relation to calcium stone formation. We defined the states which urinary excretions exceeded 95% upper confidence limits of normal controls as hyperexcretions. Hypercalciuria was more than 200 mg/day in male and female, hyperoxaluria was 50 mg/day in male and 45 mg/day in female and hyperuricosuria was 850 mg/day in male and 650 mg/day in female according to our definition. Among male calcium stone-formers, hypercalciuria was found in 45.3%, hyperoxaluria in 26.4% and hyperuricosuria in 15.1%. While in female calcium stone-formers, hypercalciuria in 23.7%, hyperoxaluria in 26.3% and hyperuricosuria in 13.2%. Of the male calcium stone-formers 57.5% showed either or both hypercalciuria and hyperoxaluria, and recurrent stone-formers also demonstrated a higher incidence among them. Excretion products of urinary calcium and oxalate were calculated and compared in each group. Calcium stone-formers showed significant high values especially in male recurrent stone-formers. The estimation by combining some risk factors will provide more useful means of assessing severity of urinary calculous diseases and therapeutic effects of their various treatments.