共查询到19条相似文献,搜索用时 93 毫秒
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分离的家兔肋软骨的生长板软骨细胞在含10%的胎牛血清的IMDM培养液中进行高密度培养。培养的软骨细胞经过增殖、分化重新构建形成了生长板样软骨组织;在组织学上,细胞的排列呈现明显的方向性,肥大细胞位于上侧、增殖细胞位于下面从而形成明显的细胞分化区带,即增殖、成熟区和肥大区,并且细胞纵向排列成柱状;在生化代谢方面,软骨细胞DNA,蛋白多糖和碱性磷酸酶的合成具有动态的严格的时间规律性,与在体生长板软骨细胞分化的进程相一致,完整地模拟了在体软骨细胞分化及其代谢的全部过程。 相似文献
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目的:研究短期高浓度氟对小鼠磨牙成釉细胞形态及骨形成蛋白-4(BMP-4)表达的影响,探讨氟对牙本质发育的相关机制。方法:选择40只4日龄的ICR小鼠为研究对象,随机分2组各20只,每组对照鼠与实验鼠各半,对实验动物进行单次腹腔注射,剂量分别为10mg/kg和20mg/kg的Na F,对照组动物则进行单次腹腔注射等剂量的Na Cl,24小时后处死动物。采用免疫组化染色观察高浓度氟对小鼠磨牙不同分化阶段成釉细胞形态及BMP-4表达的影响。结果:成釉细胞在分泌过渡期及早、晚期对短期暴露高浓度F-敏感,与对照组小鼠相比,实验组小鼠成熟期成釉细胞无明显变化,过渡期与分泌晚期成釉细胞中BMP-4的表达显著降低,差异有统计学意义(P0.05)。结论:短期高浓度氟对分泌过渡期及晚期成釉细胞中BMP-4的表达有抑制作用。 相似文献
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膜上G蛋白偶联受体(GPCRs)是骨细胞感知外部信号刺激的关键跨膜蛋白,因其在成骨细胞(OB)、软骨细胞和破骨细胞(OC)分化和功能发挥上扮演的关键角色而在骨代谢研究领域备受关注。GPCRs功能缺失或异常升高后,骨细胞内环境稳态失衡,导致OB、软骨细胞和OC分化及代谢紊乱,骨组织微细结构退化。运动通过促进骨形成并抑制骨吸收来改善骨代谢,其机制与GPCRs (如GPR48、GPR54、GPR30等)介导的关键信号途径(cAMP/PKA/Atf4、JNK/AP-1、ERK1/2等)和细胞因子(T-PINP、Nkx3.2、Sox9和Cleaved-caspase-3等)调控下游级联反应来影响OB、软骨细胞和OC分化或功能密切相关。本文通过梳理GPCRs在运动改善骨代谢中的可能机制,有助于筛选出膜上敏感GPCRs来作为骨代谢疾病药物研发“效应器”以及运动干预中的力学刺激“明星蛋白”,为骨质疏松的研究和防治提供更多靶点或视角。 相似文献
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目的研究甲状旁腺激素相关蛋白1-34(PTHrP1-34)对荷瘤小鼠骨代谢的影响,同时观察肿瘤生长情况。方法对照组、模型组、实验组4周龄健康雌性BALB/c小鼠各12只,模型组和实验组采用乳腺癌组织块悬浊液注射法制备小鼠乳腺癌模型,10d后模型组每日予以生理盐水腹腔注射,实验组每日予以PTHrP1-34400μg/(kg.bw)腹腔注射。用药35 d后测全身骨密度(BMD)、股骨灰干重比、骨代谢相关血清指标[钙(Ca)、磷(P)、碱性磷酸酶(ALP)、骨钙素(OC)、Ⅰ型胶原C-末端交联顶端肽β(β-CTX)、骨唾液酸蛋白(BSP)],剥离肿瘤比较体积与质量。结果各组Ca水平差异无显著性(P〉0.05)。与对照组和模型组比较,实验组P、β-CTX、BSP等反映骨吸收的指标显著升高(P〈0.01或P〈0.05),总ALP、BGP等反映骨形成的指标显著降低(P〈0.01或P〈0.05);实验组BMD、股骨灰干重比均显著降低(P〈0.01)。与对照组相比,模型组各指标变化差异无显著性。实验组肿瘤体积和质量显著升高(P〈0.01)。结论在PTHrP1-34的作用下,荷瘤小鼠骨吸收大于骨形成,造成溶骨性骨破坏,骨密度降低,骨破坏释放的细胞因子可能促进肿瘤生长。 相似文献
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目的:观察过量氟对绵羊肋软骨中BMP-2基因表达及分布的影响。方法:利用内蒙古内陆湖泊乌梁素海高氟水草龙须眼子菜作为饲料氟源,设计3个不同氟添加水平(50、100、150mg/kg)和1个对照组。2个月饲喂后屠宰,采用cRNA-mRNA原位杂交技术检测绵羊肋软骨中BMP-2表达及分布情况。结果:在正常生长期绵羊肋软骨中只能检测到极少量的BMP-2表达,主要集中于外边缘的成纤维细胞中;而添加高氟水草氟含量50mg/kg的试验Ⅰ组,BMP-2在成纤维细胞、幼稚软骨细胞、同源细胞群和肥大软骨细胞处均有表达;添加高氟水草氟含量100mg/kg的试验Ⅱ组,BMP-2在成纤维细胞、幼稚软骨细胞、分裂的同源细胞中表达;添加高氟水草氟含量150mg/kg的试验Ⅲ组,BMP-2在成纤维细胞、幼稚软骨细胞中表达。结论:过量氟刺激了生长绵羊软骨中BMP-2基因表达,改变了BMP-2基因的表达分布,使其在肋软骨中非正常表达;而高过量氟又直接或间接抑制了BMP-2基因在肋软骨中表达。 相似文献
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高氟低碘对Wistar大鼠大脑组织病理学及DNA损伤的影响 总被引:3,自引:0,他引:3
目的研究高氟与低碘对子代大鼠大脑组织病理学及脑细胞DNA损伤的影响。方法断乳Wistar大鼠(雌∶雄=3∶1)32只,随机分为四组:对照组,饲喂大鼠标准饲料,去离子水;高氟组,饲喂大鼠标准饲料,饮100mg/L氟化钠(NaF)去离子水;低碘组,饲喂低碘饲料(定做),去离子水;高氟低碘组,饲喂低碘饲料,饮100mg/L氟化钠(NaF)去离子水。雌雄大鼠自然交配,待子代大鼠出生后,观察其在10、20天时脑皮质、海马组织病理学变化,及30、60和90天时脑DNA的损伤。结果与对照组相比,高氟组和低碘组大鼠大脑皮质及海马内有较多神经元核固缩、核溶解及细胞轮廓不清晰。高氟低碘组,有大量神经元出现核固缩、核溶解、锥体突明显拉长等现象,并且在大鼠发育期内尤其明显。随着日龄的增加,各实验组子代大鼠脑细胞DNA损伤程度显著增加,以高氟低碘组90日龄大鼠DNA损伤最严重。结论高氟与低碘影响了大鼠大脑皮质及海马组织形态结构与引起了脑细胞的DNA损伤。 相似文献
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低氧诱导因子-1α(HIF-1α)是调节细胞对低氧应答的关键因子,可在氧含量降低时被激活,能够调节氧代谢、糖酵解等多种生理活动.骨代谢主要包括骨形成和骨吸收作用,均受到氧浓度等多种因素的调控.HIF-1α在细胞代谢、骨组织生理及病理过程的调控中起着重要的作用,能够增加骨组织的低氧耐受能力,调节骨形成和矿化过程.该文主要... 相似文献
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慢性氟暴露是世界范围内的公共卫生问题之一.为研究燃煤污染型氟中毒患者中氟暴露、骨相损伤程度与骨形成标志物血清碱性磷酸酶(ALP)、骨钙素(BGP)之间的相关关系,以贵州省织金县荷花村(燃煤污染型地方性氟中毒病区)和安顺市张官村(非氟暴露村)为调查点,采集环境样品,采用氟离子选择电极法测定环境介质及食物中的氟含量.在知情同意的原则下,对295例氟暴露和85例非氟暴露调查对象进行氟斑牙、氟骨症诊断;收集其尿液及外周血,测定尿氟(UF)浓度、ALP活性和BGP含量.结果表明: 病区环境中大米、辣椒、玉米、饮水、黏土、菜土、煤以及室内外空气氟含量均明显高于对照区,但较以往报道数据降低;随着尿氟浓度的升高,ALP活性、BGP含量显著升高,氟骨症病情差异有统计学意义,氟斑牙病情差异无统计学意义;氟骨症病情与ALP活性、BGP含量呈正相关.表明燃煤污染型低氟暴露可引起人群的骨相损害,且ALP、BGP可用于评估氟骨症患者骨转换情况,在氟骨症的辅助诊断、疗效评估中有着一定的应用价值. 相似文献
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Atay AA Kismet E Turkbay T Kocaoglu M Demirkaya E Sarici SU Congologlu A Gokcay E 《Biological trace element research》2005,105(1-3):197-203
The inhalation of a wide range of organic solvents has become popular among young adults. Toluene is one of the most commonly
used solvents in industry; it is easily available and conventient to use. Many toxicologic effects on biological systems secondary
to deliberate inhalation of toluene have been reported, but investigations on adverse effects associated with bone morbidity
is limited. The purpose of this study is to determine bone mineralization and investigate the adverse effects of toluene on
bone. The bone mineral density and content of the femoral neck of mice exposed to toluene at 300 ppm for 8 wk were measured
by dual X-ray absorptiometry and found significantly reduced compared to the control group. Chronic exposure to toluene was
found to affect bone metabolism, and toluene-induced changes could contribute to bone resorption and inhibition of bone formation.
Toluene seems to be the responsible component for the demineralizating effects of commonly abused substances, and medical
doctors must promote their education about the health hazards in those who abuse solvents especially in areas where inhalant
abuse is endemic. 相似文献
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慢性氟砷联合中毒是全世界的一个重大公共卫生问题,影响着数千万人.目前该病病因清楚,但发病机制未明,且无特效治疗方法,因此,早期预防尤为重要.生物暴露限值旨在探讨外源化学物引起机体有害效应的最高容许浓度.为了探讨氟砷混合暴露的生物暴露限值(BEL),本研究通过比较对照及氟砷联合暴露地区环境介质中的氟、砷含量,分析氟、砷与Wnt信号通路关键蛋白的剂量-效应及剂量-反应关系,利用基准剂量法估算氟砷混合暴露的生物暴露限值.结果表明: 氟砷联合暴露地区煤、黏土、室内空气、室外空气、辣椒、大米中的氟含量以及煤、黏土、室外空气、辣椒、大米中的砷含量均高于对照;随着氟、砷暴露水平的增加,糖原合酶激酶3β(GSK3β)、β-连环蛋白(β-catenin)含量以及Wnt/β连环蛋白信号通路拮抗蛋白(DKK1)、GSK3β、β-catenin的异常检出率逐渐增加,但DKK1含量显著降低;基于Wnt信号通路,氟砷混合暴露的生物暴露限值UF为0.52 mg·g-1Cr,UAs为6.59 μg·g-1Cr.本研究对于早期预防氟砷联合中毒引起的机体损伤具有重要的指导意义. 相似文献
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Robert A. Yokel 《Biological trace element research》1983,5(6):467-474
To determine the distribution of aluminum (A1) following systemic exposure, female New Zealand white rabbits were given 20 subcutaneous injections, over 4 weeks, of 0, 25, 50, 100, 200, or 400 μmol A1/kg/injection, as the lactate salt. They were sacrificed 5 weeks after completion of injections and selected tissues removed for graphite furnace atomic absorption analysis of tissue A1 content. Rabbits not receiving A1 injections had mean tissue A1 concentrations ranging from 1.5-7.4 μg/g. Bone was higher, 18.7 μg/g. All tissues, except for muscle, demonstrated an increase in A1 concentration correlating with the A1 exposure. After 400 μmol A1/kg/injection for 20 injections, tissue A1 concentrations were: bone 90, heart 12, kidney-cortex 1290, kidney-medulla 245, liver 246, lung 19, and spleen 465 μg A1/g. The average of the 5 central nervous system regions sampled (frontal grey, white, hippocampus, cerebellum, and spinal cord) rose 53% over controls. Determination of A1 in kidney, liver, or bone may be useful in diagnosis of A1 overload conditions in humans (dialysis encepthalopathy, dialysis osteomalacia, and parenteral nutrition-associated osteomalacia). The rabbit appears to be a useful model to further study A1 intoxication syndromes. 相似文献
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BackgroundDespite their differences in physicochemical properties, both uranium (U) and fluoride (F) are nephrotoxicants at high doses but their adverse effects at low doses are still the subject of debate. METHODS: This study aims to improve the knowledge of the biological mechanisms involved through an adaptive response model of C57BL/6 J mice chronically exposed to low priming doses of U (0, 10, 20 and 40 mg/L) or F (0, 15, 30 and 50 mg/L) and then challenged with acute exposure of 5 mg/kg U or 7.5 mg/kg NaF.ResultsWe showed that an adaptive response occurred with priming exposures to 20 mg/L U and 50 mg/L F, with decreased levels of the biomarkers KIM-1 and CLU compared to those in animals that received the challenge dose only (positive control). The adaptive mechanisms involved a decrease in caspase 3/7 activities in animals exposed to 20 mg/L U and a decrease in in situ VCAM expression in mice exposed to 50 mg/L F. However, autophagy and the UPR were induced independently of priming exposure to U or F and could not be identified as adaptive mechanisms to U or F.ConclusionTaken together, these results allow us to identify renal adaptive responses to U and F at doses of 20 and 50 mg/L, probably through decrease apoptosis and inflammatory cell recruitment. 相似文献
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Zinc and fluorides are capable of modifying the process of bone formation and mineralization. Statistically significant differences
have been revealed in the content of zinc and fluorides between structures of the femur in chicken. The content of zinc in
compact bone remained constant during the first 50 d of life. Lower and less stable contents were found in spongy bone and
bone marrow. The content of fluorides in compact bone was higher than in spongy bone. The lowest concentrations of zinc and
fluorides were found in articular cartilage and were further reduced at the end of observation. Correlations revealed between
the content of zinc and fluorides point to structural and functional relationships between these elements in various parts
of the bone. 相似文献
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Transducin, the guanyl nucleotide-binding protein of the retinal light-activated cGMP phosphodiesterase system, is structurally and functionally similar to the inhibitory and stimulatory guanyl nucleotide-binding proteins, Gi and Gs, of the adenylate cyclase complex. All are heterotrimers composed of alpha, beta, and gamma subunits. Gs and Gi can be activated by NaF with AlCl3 as well as by agonists acting through specific receptors. The effects of NaF and AlCl3 on transducin were investigated in a reconstituted system consisting of the purified subunits of transducin (T alpha, T beta, gamma) and rhodopsin. NaF noncompetitively inhibited the GTPase activity of T alpha in a concentration- and time-dependent manner. Inhibition by NaF was enhanced synergistically by AlCl3 which alone only slightly inhibited GTPase activity. None of the other anions tested reproduced the effect of fluoride. Fluoride inhibited [3H]guanosine 5'-(beta, gamma-imido)triphosphate binding to T alpha and release of bound GDP. The ADP-ribosylation of T alpha by pertussis toxin and binding of T alpha to rhodopsin, both of which are enhanced in the presence of T beta gamma, were inhibited by NaF and AlCl3. These findings are consistent with the hypothesis that fluoride enhances the dissociation of T alpha from T beta gamma, resulting in the inhibition of GTP-GDP exchange, and therefore, GTP hydrolysis. 相似文献
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Fluoridated dental care products are used to prevent dental decay. Up to now, there are no data available on whether the fluoride (F-) component of these products affects the bactericidal activity of salivary polymorpho-nuclear leucocytes, which are involved in the protection of the oral mucosa against infection. Therefore, after determining the concentration/time profile of F- in mixed saliva of healthy subjects after topical application of 0.5 g of a 1.25% F- containing gel, unstimulated and fMLP-stimulated polymorphonuclear leucocytes (PMNs) were shortly exposed to these F- concentrations and the generation of superoxide and hypochloric acid were measured, as well as the liberation of lysomal enzymes, and correlated with the cellular Ca2+ and cAMP-levels. The results show that F-, at concentrations as retained in saliva, did not activate the oxidative burst in unstimulated PMNs. In fMLP-activated PMNs, F-suppressed the receptor-mediated increase in the oxidative burst and the liberation of fl-glucuronidase by reduction of the availability of extracellular Ca2+ and, thus, the influx of Ca2+ necessary to couple completely the fMLP signal to effector pathways. These F- concentrations neither altered the liberation of Ca2+ from internal stores nor induced a rise in cAMP. The possible clinical consequences of these results for xerostomic patients with respect to the generation of HOSCN/OSCN/SCN in saliva an important non-immune factor for oral health, are dicussed. 相似文献
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Beryllium and aluminum fluorides are good phosphate analogues. These compounds, like orthovanadate, form stable complexes with myosin subfragment 1 (S1) in the presence of MgADP. The formation of the stable S1-nucleotide complexes is characterized by the loss of ATPase activity. For the complete loss of ATPase activity there was necessary a higher concentration of aluminum than of beryllium or vanadate. In the presence of MgATP the onset of the inhibition is delayed, which indicates that stable complexes cannot form when a specific site is occupied by the gamma-phosphate of ATP or by P(i) derived from the gamma-phosphate. The half-lives of the S1-MgADP-(BeF3-), S1-MgADP-(AlF4-), and S1-MgADP-Vi complexes at 0 degrees C are 7, 2, and 4 days, respectively. In the presence of actin the rate of decomposition of all of the complexes is significantly enhanced; however, the order of decomposition is reversed, the fastest rate being observed with beryllium and the slowest with aluminum. The formation of the S1-MgADP-(BeF3-) and S1-MgADP-(AlF4-) complexes is accompanied by an increase in tryptophan fluorescence similar to that observed upon addition of MgATP to S1. The fluorescence increase develops rather slowly, by suggesting that the rate-limiting step in the formation of the stable complex is an isomerization. The rate of the fluorescence change accompanying the formation of the Be complex is faster than that for the Al complex. Addition of vanadate to S1 causes a static quenching of the tryptophan fluorescence.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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Occupational and environmental aluminum (Al) exposure cause serious health problems by interaction with biological systems.
Al is one of the most documented metals because its cellular targets are unclear biochemical processes and membranes of organisms.
The major aim of the present study was to investigate the alteration of serum and urine aluminum in occupational exposure
and to observe whether the metal exposure could cause any changes in pteridine-pathway-related critical compounds such as
urinary neopterin and biopterin and blood dihydropteridine reductase (DHPR). In this study, determination of the metal concentrations
was carried out in Al-exposed workers (n=23) and healthy volunteers (n=18) by using a tomic absorption spectrometer. DHPR enzyme activity and levels of neopterin and biopterin were detected by
spectrophotometric and high-performance liquid chromatographic methods, respectively. It was found that occupational exposure
to the metal led to a statistically significant increase in serum Al levels compared to the controls (p<0.05). At the same time, urinary neopterin and biopterin concentrations of the exposed group were higher than nonexposed
subjects (both p<0.05). The correlations among Al levels and DHPR activity, magnesium concentration in serum and urine, working years, smoking
status, and age were evaluated. 相似文献