Effects of simultaneous increases in dietary phosphorus and magnesium concentrations on nephrocalcinosis and kidney function in female rats.

The effects of simultaneous increases in dietary phosphorus (P) and magnesium (Mg) concentrations while maintaining a constant P:Mg ratio on nephrocalcinosis and kidney function in female rats was investigated. Female Wistar rats were fed a control diet (3.12 g P, 0.51 g Mg per kg diet) or a diet having either 3 times the control P and Mg concentrations (3-fold diet; 9.25 g P and 1.42 g Mg per kg diet) or 5 times the control concentrations (5-fold diet; 14.97 g P and 2.37 g Mg per kg diet) for 21 d. The three experimental diets all had same P:Mg molar ratios (control diet; 4.81, 3-fold diet; 5.11, 5-fold diet; 4.96). The 3-fold diet had no significant influence on kidney calcium (Ca), Mg or P concentrations. However, kidney Ca, Mg and P concentrations were significantly higher in rats fed the 5-fold diet than in rats fed the control or 3-fold diets. No significant differences in creatinine clearance were observed among the three groups. Urinary albumin and beta 2-microglobulin excretion were higher in rats fed the 5-fold diet than in rats fed the control or 3-fold diets, while the 3-fold diet had no significant influence on the urinary albumin and beta 2-microglobulin excretion. These results suggest that absolute concentrations of dietary P and Mg are important factors with regard to the development of nephrocalcinosis and diminished kidney function.     

Decreased absorption and retention rates of magnesium in the rats fed on spinach-supplemented diets: possible explanations.

We studied the bioavailability of magnesium (Mg) in spinach after boiling with distilled water, using Mg-deficient growing male rats. The rats were fed a semipurified diet (Mg:0.063 per cent (w/w)) for 3 days. then a Mg-deficient diet (Mg:0.001 per cent (w/w)) for 5 days. They were then divided randomly into 7 groups of 6 rats each, and fed the semipurified diet (Mg: 0.063, 0.045 or 0.027 per cent (w/w)), or the spinach-supplemented diet (10 per cent (w/w) dried and powdered spinach after boiling with distilled water for 3 min at 100 degrees C). The Mg content of the diets supplemented with spinach grown on chemical nutrients, and on manure from pigs, cattle and fowl, was 0.069, 0.051, 0.043 and 0.036 per cent (w/w), respectively. Water intake and volumes of urine and faeces were significantly greater in the rats fed the spinach-supplemented diets than in those fed the semipurified diets. Apparent absorption of Mg, and urinary and faecal excretions of Mg were directly related to Mg intake: no significant difference was observed amongst the groups. Both the ratios of Mg absorption and retention were significantly lower in the rats fed diets supplemented with spinach than in those fed semipurified diets. The plasma Mg level was directly related to Mg intake in the rats fed the semipurified diets and the spinach-supplemented diets. However, the plasma Mg level in the rats fed spinach grown organically on manure from fowl tended to be higher than in the other groups. From these results, it was concluded that bound Mg in spinach was effectively utilized by Mg-deficient rats, however, the absorption and retention rates of Mg in rats fed diets supplemented with spinach were decreased. Possible explanations were discussed.     

三聚氰胺亚慢性毒性实验研究

目的研究三聚氰胺亚慢性染毒对大鼠的毒性作用。方法 SD大鼠140只,雌雄各半,随机分为4组,每组各28只。给药组以三聚氰胺0.25、0.5、1.0 g/kg进行大鼠灌胃,空白对照组给予4 ml/kg生理盐水溶液灌胃,给药30 d,停药后恢复观察15 d,分别在实验的第30、45天末取血及主要脏器,观察三聚氰胺对大鼠生长、组织病理变化、血常规、血液生化指标的影响。结果三聚氰胺对SD大鼠生长没有明显的影响,血常规指标检查结果均在正常范围内;给药末期及恢复期,0.5 g/kg组、1.0 g/kg组大鼠肾脏、膀胱质量及脏器系数高于空白对照组,差异有统计学意义（P〈0.01）;0.5 g/kg、1.0 g/kg组大鼠BUN、CRE、UA含量均较高,差异有统计学意义（P〈0.05）;1.0 g/kg组,肾组织间质有大量炎细胞浸润,肾小管变性、坏死,肾剖面可见大量放射状结晶。给药末期0.5 g/kg组、1.0 g/kg组尿潜血阳性率与空白对照组比较,差异有统计学意义（P〈0.05）。结论三聚氰胺对SD大鼠有亚慢性毒性作用,毒性作用的主要靶器官是肾、膀胱,亚慢性染毒可严重损伤肾功能,对大鼠造成的损伤在短期内不可逆,有迟发性毒性作用。     

The phytoestrogen alpha-zearalenol reverses endothelial dysfunction induced by oophorectomy in rats

It has been shown recently that alpha-zearalenol, a resorcyclic acid lactone, prevents bone loss in a rat model of postmenopausal bone loss. We have therefore investigated the effects of this phytoestrogen on endothelial dysfunction induced by estrogen deficiency in rats. Female mature Sprague-Dawley rats underwent a bilateral oophorectomy (OVX rats). Sham-operated animals (sham OVX rats) were used as controls. Three weeks after surgery, animals were randomized to the following treatments: alpha-zearalenol (1 mg/kg/day, i.m., for 4 weeks), 17beta-estradiol (20 microg/kg/day, i.m., for 4 weeks), or their vehicle (100 microl, i.m., of cottonseed oil). Two other groups of rats were treated with alpha-zearalenol or 17beta-estradiol plus the pure estrogen receptor antagonist ICI 182780 (2.5 mg/kg/day, i.m., for 4 weeks). Mean arterial blood pressure (MAP), heart rate (HR), total plasma cholesterol, plasma estradiol, and plasma alpha-zearalenol were studied. We also investigated endothelial-dependent (acetylcholine, 10 nM to 10 microM) and endothelial-independent (sodium nitroprusside, 15 nM to 30 nM) relaxation of aortic rings, as well as N(G)-methyl-L-arginine (L-NMA: 10 to 100 microM)-induced vasoconstriction and calcium-dependent nitric oxide synthase (cNOS) activity in homogenates of lungs taken from both sham OVX rats and OVX rats. Untreated OVX rats had, compared with sham OVX animals, unchanged body weight, MAP, HR, and plasma cholesterol. In contrast oophorectomy reduced plasma estradiol levels (OVX, 2 +/- 0.5 pg/ml; sham OVX, 35 +/- 6 pg/ml), impaired endothelial-dependent relaxation and blunted L-NMA-induced contraction (L-NMA 100 microM: sham OVX, 2.7 +/- 0.3 g/mg tissue; OVX, 1.3 +/- 0.1 g/mg tissue). Moreover OVX rats showed a reduced calcium-dependent NO synthase (cNOS) activity. Treatment with alpha-zearalenol or with 17beta-estradiol reverted the endothelial dysfunction and increased cNOS activity in lung homogenates. These effects were abolished by the pure estrogen receptor antagonist ICI 182780. Our data suggest that alpha-zearalenol improves endothelial-dependent relaxation in OVX rats through an estrogen receptor-mediated effect.     

低剂量棉酚与甾体激素联合应用对生精细胞凋亡和iNOS蛋白表达的影响

目的 研究低剂量棉酚与甾体激素联合应用(棉甾联合用药)对大鼠睾丸生精细胞凋亡和诱导型一氧化氮合酶(iNOS)蛋白表达的影响. 方法 本实验采用大鼠喂服棉酚12.5mg/(kg.d)+激素[去氧孕烯125μg/(kg.d)+炔雌醇25μg/(kg.d)+十一酸睾丸酮100mg/(kg.d)]联合用药的方式,与单独喂服相同剂量的棉酚或激素的大鼠及喂服甲基纤维素溶剂的大鼠相对照,通过原位缺口末端标记(TUNEL)染色,观察生精细胞凋亡的情况;通过免疫组织化学染色和免疫印迹法,观察诱导型一氧化氮合酶(iNOS)蛋白表达的变化. 结果 TUNEL染色显示,在正常对照组,阳性着色主要分布在Ⅶ、Ⅷ、Ⅸ期生精小管的残余体中,偶见于粗线期精母细胞中.棉甾联合用药组和激素组,阳性着色主要分布在粗线期精母细胞中,随用药时间的延长,阳性着色的细胞数量增多(P＜0.01).iNOS免疫组织化学显示,在正常对照组,在残余体、精原细胞和粗线期精母细胞中的表达具有期依赖性.在Ⅶ、Ⅷ、Ⅸ期生精小管,iNOS主要在残余体中表达;在IX-XII期生精小管,精原细胞和粗线期精母细胞的核中可见少量表达.在棉甾联合用药组,iNOS在残余体中的表达,随用药时间的延长表达量降低(P＜0.05);iNOS在粗线期精母细胞、精原细胞胞核中的表达,随用药时间的延长表达量增高(P＜0.05).iNOS在正常对照组的间质细胞中持续表达,棉甾联合用药组4周降至最低,3时间点表达量无统计学差别. 结论 iNOS蛋白在低剂量棉酚加甾体激素联合应用大鼠睾丸中各部位的表达变化趋势不一致,分别产生不同的功能;生精细胞凋亡数增加,可能与iNOS的表达增多有关.     

落新妇甙对大鼠肺移植排斥反应的抑制作用

目的:探讨落新妇甙对大鼠肺移植排斥反应的抑制作用。方法:采用大鼠左侧单肺移植模型。随机将肺移植后的40只大鼠分为4组:A组肺移植后用生理盐水(1ml/天)灌胃,B组肺移植后用环孢素A(5mg/kg/天)灌胃,C组肺移植后用落新妇甙(1ml/kg/天)灌胃,D组肺移植后用环孢素A(2.5mg/kg/天)及落新妇甙(1ml/kg/天)灌胃。术后第10天切取移植肺观察肺急性排斥反应分级情况。结果:B组、C组及D组移植肺排斥反应分级均低于A组(P<0.05～0.01);D组移植肺急性排斥反应最轻,优于C组(P<0.05)和B组(P<0.01)。结论:落新妇甙对肺移植排斥反应有较强的抑制作用,并与环孢素A有协同作用。     

Effects of cyclosporin A and cyclophosphamide on Peyer's patches in rat, exposed in utero and neonatally or during adult age

The effects of cyclosporin A (CY) and cyclophosphamide (CPS) on Peyer's patches (PP) were studied in Wistar rats, exposed in utero and neonatally or during adult age. In one study, pregnant dams received 5 or 15 mg/kg bw/day CY from gestation day 6 to day 21 of lactation. In two other studies, animals were exposed at young adult age: female rats received orally 5 or 20 mg/kg/day CY or 5 or 10 mg/kg bw CPS for 4 weeks; males received orally 5 mg/kg bw CPS for 4 weeks, or a single i.v. injection of 50 mg/kg bw CPS. Upon in utero and neonatal exposure, the numbers of grossly observed PP were increased in male pups from the high-dose CY dams at 70 days of age. Exposure to high-dose CY at adult age only tended to decrease the numbers of PP; germinal center development was reduced in the PP from the middle segment of the small intestines, as examined microscopically. Exposure to both doses CPS at adult age reduced the numbers of PP and reduced germinal centre development and the number of lymphocytes in all compartments of PP. It was concluded that the effects of CPS and CY could be established by counting the number of grossly visible PP and by microscopic observation of PP, provided that regional differences of PP were taken into account. Moreover, the type of effects of an immunotoxic agent may vary with age of exposure.     

Calcium and magnesium content in hard tissues of rats under condition of subchronic lead intoxication.

Lead manifests toxic effects in almost all organs and tissues, especially in: the nervous system, hematopoietic system, kidney and liver. This metal has a special affinity for deposition in hard tissue, i.e., bones and teeth. It is generally believed that the main mechanism of its toxicity relies on its interaction with bioelements, especially with Ca and Mg. This article analyses the influence of Pb poisoning on Ca and Mg content in hard tissues, (mandible, femur, teeth and skull) of female and young rats. Experiments were carried out on 60 female rats, AO breed, and on 80 of their young rats (offspring). Female rats were divided into three groups: the first one was a control group, the second one received 100 mg/kg Pb2+ kg b.wt. per day in drinking water, the third one received 30 mg/kg Pb(2+) kg b.wt. per day in drinking water. Young rats (offspring) were divided into the same respective three groups. Lead, calcium and magnesium content in hard tissues (mandible, femur, teeth-incisors and skull) was determined by flame atomic absorption spectrophotometry in mineralized samples. There was a statistically significant Pb deposition in all analyzed female and young rat hard tissues. Ca and Mg contents were significantly reduced in all female and young rat hard tissues. These results show that Pb poisoning causes a significant reduction in Ca and Mg content in animal hard tissues, which is probably the consequence of competitive antagonism between Pb and Ca and Mg.     

Effect of OS-0689, a novel SERM, on periarterial nerve function in tail arteries of ovariectomized rats

OBJECTIVE: We have previously shown that OS-0689 attenuates the rise in tail skin temperature of ovariectomized rats, which is believed to be relevant to human symptoms of hot flush. In this study, we elucidate the mechanism underlying the ameliorating effects of OS-0689 on elevated tail skin temperature. METHODS: Female Sprague-Dawley rats were ovariectomized and orally treated with OS-0544 (1 mg/kg), OS-0689 (3 mg/kg; (+)-enantiomer of OS-0544) or 17beta-estradiol (3 mg/kg; E2) for 1 week. At 1, 3 or 6 weeks after ovariectomy, the vasoconstrictions and vasorelaxations induced by periarterial nerve stimulation (PNS), l-noradrenaline (NA), and rat calcitonin gene-related peptide (CGRP) in isolated tail arteries were compared between OVX and sham-operated rats. RESULTS: Three weeks after ovariectomy, vasoconstrictions in response to PNS and NA in the arteries of OVX rats were markedly less than those in the arteries of sham-operated rats. However, at 1 and 6 weeks after ovariectomy the stimuli-induced vasoconstrictions in the arteries of OVX rats were greater than those of sham-operated rats. Moreover, NA reactivity was not attenuated in the mesenteric arteries at 3 weeks after ovariectomy. OS-0544, OS-0689 and E2 prevented the decrease in vasoconstrictions in the tail arteries. Vasorelaxations in response to PNS and rat CGRP were significantly greater in the arteries of OVX rats than in those of the sham-operated rats. OS-0689 inhibited the increase in vasorelaxation induced by both stimuli, whereas E2 had no effects. CONCLUSIONS: Ovariectomy not only decreases adrenergic function but also enhances CGRPergic function in rats' tail arteries. OS-0689 improves both impairments and thereby improves on rat hot flush.     

Onset of nephrocalcinosis depends on dietary phosphorus concentration in male rats fed a magnesium-deficient diet.

Although a magnesium (Mg)-deficient diet is generally known to induce nephrocalcinosis, our previous study observed that despite the administration of a Mg-deficient diet, the kidney calcium (Ca) and phosphorus (P) concentrations were not increased in male rats. We speculated that this result was due to the P concentration of the experimental diet based on the AIN-93G formula used in the previous study. In the present study, male rats were fed modified AIN-93G diets containing the two different Mg concentrations [0.5 g per kg diet (normal-Mg) or Mg-free (Mg-deficient)] and three different P concentrations [3 (3-P), 5 (5-P) or 7 (7-P) g per kg diet]. By histological examination of the kidney, nephrocalcinosis was not observed in rats fed on the Mg-deficient diet containing 3-P While nephrocalcinosis appeared in rats fed on the Mg-deficient diet containing 5-P and 7-P The degree of nephrocalcinosis was severe in rats fed on the Mg-deficient diet containing 7-P compared with rats fed on the Mg-deficient diet containing 5-P These results demonstrated that the Mg-deficient diet based on AIN-93G formula dose not induce nephrocalcinosis and that the Mg-deficient diet based on AIN-93G formula with increased dietary P concentrations induces nephrocalcinosis in male rats. We suggest that the onset of nephrocalcinosis could depend on the dietary P concentration in male rats fed on a Mg-deficient diet.     

Estrogen effects on the hyperactivity induced by (+)-MDMA and cocaine in female rats

This study compared the effects of estrogen (E) on the hyperactivity induced by (+)-3,4-methylenedioxymethamphetamine (MDMA) with E effects on cocaine-evoked hyperactivity in female rats. Sprague-Dawley rats were ovariectomized (OVX); half of them received a 17beta-estradiol (E2) implant (OVX + E). Three weeks later, rats received saline, (+)-MDMA (1, 2, or 4 mg/kg) or cocaine (5, 10, or 20 mg/kg), and locomotor activity was monitored. OVX + E rats exhibited greater locomotor hyperactivity in response to both psychostimulants than did OVX rats. The enhanced response to cocaine appeared within 5 min following drug injection whereas the enhanced response to (+)-MDMA was delayed for approximately 30 min. The differential effects of E on hyperactivity may be due to the unique profiles of DA and 5-HT in response to (+)-MDMA and cocaine.     

去卵巢和雌激素替代治疗对心肌细胞基因表达谱的影响

目的：本实验通过高通量的cDNA微阵列技术，研究去卵巢和雌激素替代治疗对心肌细胞基因表达谱的影响，寻找雌激素的靶基因。方法:用 1 400 个基因构建的cDNA微阵列检测假手术组（Ⅰ）、去卵巢组（Ⅱ，去势组）和雌激素替代治疗组（Ⅲ，替代组）3组SD雌鼠心肌组织的基因表达差异,随机选2个基因用半定量RT-PCR验证检测结果。结果:假手术组和去势组共检出心肌差异表达的基因177个，其中去卵巢导致上调的基因91个，下调的基因86个；去势组和替代组共检出心肌差异表达的基因164个，其中雌激素替代治疗后导致上调的基因113个，下调的基因54个。Ⅰ/Ⅱ和Ⅲ/Ⅱ比较，相同的差异表达基因54个，雌激素明显影响心肌膜通道和载体（18个）、细胞受体（9个）、信号转导相关基因（7个）和细胞代谢（6个）的mRNA水平。而大部分基因（45个）是在去势组表达下调，在雌激素替代组表达上调。RT-PCR实验证实了cDNA微阵列结果 。结论：长期雌激素替代治疗明显影响心肌细胞膜通道和载体、信号转导、细胞受体和细胞代谢等相关基因的表达。长期雌激素替代治疗可通过增加Na+,K+-ATPase和Na+/H+交换蛋白的基因表达，稳定心肌细胞内Na+和K+的浓度。雌激素还可抑制多巴胺受体基因的表达，预防心肌肥大、充血性心衰等心脏疾病的发生。     

Comparative effects of milk and soymilk on bone loss in adult ovariectomized osteoporosis rat

The present study was designed to investigate the comparative effects of milk and soymilk on the bone morphology of ovariectomized rat model with postmenopausal osteoporosis. Fourty 12-week-old female Spraque-Dawley rats were randomly divided into the following 5 groups: intact control (control), sham-operated (sham), ovariectomized (OVX), ovariectomized and fed milk (milk), ovariectomized and fed soymilk (soymilk) groups. Rats of OVX, milk and soymilk groups were bilaterally ovariectomized. Milk or soymilk of 3 ml was administered by gavage via an intragastric tube per day for 6 weeks. The distal femoral metaphysis was studied morphologically, together with bone mineral density (BMD), serum parathyroid hormone (PTH) and estradiol levels. In the OVX group, the trabecular bone volume was significantly reduced. The percentage area of resorbing surface was high. In the soymilk group, the trabecular bone volume was 68% higher and the percentage area of resorbing surface was 18% lower as compared with the OVX group. The serum estradiol level rose 48% and the serum PTH level fell 26% in the soymilk group. In the milk group, the trabecular bone volume had the tendency to be high, but there was no significant change of the bone morphology. The present study provides certain evidence that the soymilk has beneficial effects in preventing bone loss in rats induced by ovarian hormone deficiency.     

Effects of colchicine treatment on rat intestinal disaccharidase activities.]

The changes in morphology and proliferation kinetics produced by colchicine in the intestinal mucosa are known. Contrarily, the functional changes have yet not been investigated systematically. The aim of this study is to investigate the effects of colchicine treatment on rat intestinal disaccharidase activities. Material and methods: For the experiments male SPF-Wistar rats, body weight 180--200 g (supplied by Mus-Rattus AG, 8011 Brunnthal, FRG) were used. The animals were kept under constant conditions (6 rats per cage) and fed Altromin (Altromin Gmb H,Lage/Lippe), tap water ad libitum. Per day 6 animals of each test group were scarificed by cervical dislocation at defined time. About 3 cm of the intestine were removed 8--10 cm distally of the pylorus and cut longitudinally. After cautious cleaning the mucosa was detached using a scalpel. The thus obtained specimens of the mucosa were frozen at -- 20 degrees C in an air-tight humidity chamber and preserved there until further handling. For histological examination the correspondent parts of the intestine were fixed in 10% formol. From each specimen 4 different stainings were made (haematoxylin-eosin, Giemsa, PAS and Feulgen stain). Per test series 60--66 rats were used. The following doses of colchicine were applied: 1 X 1.0 mg/kg body weight, 1 X 0.5 mg/kg body weight, 5 X 0.1 mg/kg body weight within 24 hours. The single doses were dissolved in about 0.5 physiological saline and applied intraperitoneally. In each 6 rats per group the activities of the following diasccharidases were measured at 24 hours intervals from the 1st to 10th or 14th day: sucrase, maltase, lactase, and cellobiase. The enzyme activities were determined after the two-step method developed by DAHLQVIST (5,6) which can be used as micromethod. The ascertained enzyme activities were always related to the protein content. Protein determination was done after the method of Folin-Ciocalteu as modified by LOWRY et al. (14). The enzyme activities were expressed in international units per g protein (U/g protein). the results obtained were statistically ascertained by the non-parametric test after Kruskal-Wallis, variance analysis with linear contrasts after Scheffe as well as by double variance analyses (26).     

Determination of effective dose combination of Azadirachta indica leaf extracts and diminazene diaceturate in the treatment of experimental Trypanosoma brucei brucei infection in rats

This study investigated the effective dose of methanolic Azadirachta indica leaf extracts, MAILE, combined with diminazene diaceturate, DDA, in the treatment of experimental Trypanosoma brucei brucei infection in rats. Acute toxicity study of the drug and extract combinations was carried in non-infected rats. Eleven different groups of ten rats each were used. Ten out of the eleven groups were infected with T. brucei brucei and used to determine the effective dose of MAILE and DDA combination to be used in the treatment of the infection. All the infected rats were treated, viz, 7.0 mg/kg body weight (bw) DDA plus 500 mg/kg bw MAILE (group 1); 7.0 mg/kg body bw DDA plus 250 mg/kg bw MAILE (group 2); 7.0 mg/kg body bw DDA plus 125 mg/kg bw MAILE (group 3); 3.5 mg/kg body bw DDA plus 500 mg/kg bw MAILE (group 4); 3.5 mg/kg body bw DDA plus 250 mg/kg bw MAILE (group 5); 3.5 mg/kg body bw DDA plus 125 mg/kg bw MAILE (group 6); 1.8 mg/kg bw DDA plus 500 mg/kg bw MAILE (group 7); 1.8 mg/kg bw DDA plus 250 mg/kg bw MAILE (group 8); 1.8 mg/kg body bw DDA plus 125 mg/kg bw MAILE (group 9). Two other groups, infected untreated (group 10) and uninfected untreated (group 11), served as negative and positive control, respectively. The parameters assessed to determine the effective dose combination of the two were onset of parasitaemia (OP), level of parasitaemia (LOP), clearance of parasites post-treatment (COPPT), relapse of infection period (RIP), erythrocyte counts (EC), packed cell volume (PCV) and total leucocyte counts (TLC). There was no significant difference (p?<?0.05) in OP between the groups. A day following treatment, the LOP of groups 1, 2, 3 and 4 was found to be significantly lower (p?<?0.05) than that of groups 5 and 6 (p?<?0.05) which in turn was lower (p?<?0.05) than that of groups 7, 8 and 9, respectively. The mean COPPT of groups 5 and 6 was significantly (p?<?0.05) longer than that of groups 1, 2, 3 and 4. There was no significant difference (p?<?0.05) in the mean COPPT among groups 1, 2, 3 and 4. There was no clearance of parasites in groups 7, 8 and 9. The mean RIP of group 5 and 6 was significantly shorter (p?<?0.05) than in group 4. There was no relapse of infection in group 1, 2 and 3 rats. Rats in groups 1, 2, 3 and 4 had significantly higher (p?<?0.05) PCV, EC and TLC 10 days post-treatment, and that trend continued throughout the experimental period when compared to other infected groups. It was concluded that dose combination of 125 mg/kg bw extract plus 7 mg/kg bw DDA was the best dose combination judging from the parameters assessed.     

环孢菌素A对大鼠腹主动脉球囊损伤后内膜增生的抑制作用

目的: 探讨环孢菌素A对大鼠腹主动脉球囊损伤后内膜增生的影响。方法: 雄性SD大鼠36只,随机分为假手术组(n=12)、球囊损伤组(n=12)和环孢菌素治疗组(n=12)。环孢菌素组大鼠行腹主动脉球囊损伤术前3 d开始每天灌喂环孢菌素A 12.5 mg/kg,假手术组和球囊损伤组灌喂等容积的水,直至术后30 d。球囊损伤术后30 d取材,血管组织作HE染色、免疫组化检测钙调神经磷酸酶(CaN)在血管壁中的表达,光学显微镜观察病理学改变;rea1-time PCR技术检测血管壁组织中CaN和活化T细胞核因子3(NFATc3)的表达变化。结果: 球囊损伤后血管壁出现新生内膜,形成的新生内膜厚度不均。环孢菌素治疗组与球囊损伤组相比较,内膜增生减轻,内膜/中膜厚度明显降低(P<0.05)。免疫组化检测血管壁上CaN表达,环孢菌素治疗组明显低于球囊损伤组 (P<0.05)。大鼠腹主动脉损伤后,损伤血管壁组织CaN和NFATc3 mRNA表达升高,环孢菌素治疗组与球囊损伤组相比表达明显减少(P<0.05)。结论: 环孢菌素A可能通过抑制CaN-NFATc途径减轻球囊扩张术后动脉再狭窄。     

Magnesium fluxes during lactation in the rat

Lactating rats fed a 0.055% Mg diet transferred 5.5 +/- SEM 0.3 mg per day of Mg into milk but remained in a slightly positive Mg balance by increasing both food consumption and fractional intestinal Mg absorption. Urinary Mg excretion increased continually during the course of lactation to values double those of non-lactating rats.     

Therapeutic effects of tetrathiomolybdate on hepatic dysfunction occurring naturally in Long-Evans Cinnamon (LEC) rats: a bona fide animal model for Wilson's disease.

Long-Evans Cinnamon (LEC) rats were fed a diet containing 7 ppm Cu and 30 ppm Cu from 60 days after birth. Fischer (Fischer group) and LEC (LEC-control group) rats fed a 7 ppm Cu diet showed normal growth throughout the whole period (60 to 125 days after birth). On the other hand, LEC rats fed the 30 ppm Cu diet had decreased body weight and showed slight jaundice at around 100 days after birth. Tetrathiomolybdate (TTM, 10 mg/kg bw) was injected sub-cutaneously at 101 and 105 days after birth into half of the LEC rats fed the 30 ppm Cu diet. LEC rats given TTM (LEC+TTM group) recovered their body weight and the jaundice rapidly disappeared. However, LEC rats without TTM (LEC-TTM group) had sharply decreased body weight and showed severe jaundice at 103 days after birth. The hepatic Cu concentration in LEC+TTM rats (460 micrograms/g) exceeded that of LEC-control rats (330 micrograms/g) at 125 days after birth. Our data suggest that TTM is effective for treatment of acute hepatic injury in the LEC rat.     

The effects of hyaluronan on bone resorption and bone mineral density in a rat model of estrogen deficiency-induced osteopenia

Hyaluronan, or hyaluronic acid (HA), is an essential component of extracellular matrices. HA of appropriate molecular weight and concentration can induce osteoblast differentiation and bone formation in vitro. The aim of our study was to evaluate the effects of HA of different molecular weights on ovariectomy (OVX)-induced bone loss in rats. Adult female Sprague Dawley rats were subjected to bilateral OVX or sham surgical procedure (sham). OVX rats were treated with: HA of molecular weight of 0.75 MDa at a dose of 1 mg/kg/day and with HA of molecular weight of 1.62 MDa at a dose of both 0.5 mg/kg/day and 1 mg/kg/day. HA was applied orally once a day during the 8-week period after ovariectomy. Body weight, urinary pyridinoline (Pyr), deoxypyridinoline (DPyr) corrected for urinary creatinine, serum nitrite/nitrate concentrations and whole body and femoral bone mineral density (BMD) were measured. HA treatment had no effect on the body weight gain in OVX rats. Excretion of urinary Pyr and Dpyr significantly increased in OVX rats compared to sham controls. The higher molecular weight HA (1.62 MDa) significantly reduced urinary Pyr and DPyr concentrations measured on day 28 after ovariectomy (p < 0.001). Serum concentrations of nitric oxide metabolites, nitrite/nitrate significantly decreased in OVX rats in comparison with sham controls (p < 0.001). HA of both 0.75 MDa and 1.62 MDa molecular weights significantly enhanced serum nitrite/nitrate concentrations in OVX rats. There was a clear reduction of whole body and femoral BMD in untreated OVX rats. The higher molecular weight HA decreased both whole body and femoral BMD loss. Our results show that orally applied HA of high molecular weight (1.62 MDa) inhibits bone resorption and provides a protective effect on bone density in ovariectomized rats.