硒、钼、硼对氟中毒大鼠成釉细胞形态及PCNA、C-myc表达变化的影响

目的 观察硒、钼、硼对氟中毒大鼠成釉细胞形态及增殖细胞核抗原(PCNA),C-myc 基因表达变化的影,气方法大鼠分组均喂以含F-45 mg/L的蒸馏水及含不同浓度硒、钼、硼的饲料,建立微量元素拮抗氟中毒的大鼠模型.采用HE染色及免疫组化的方法观察氟对成釉细胞的影响,采用图像分析技术时免疫组化结果进行量化分析.结果 实...     

尿羟脯氨酸在微量元素抗氟疗效评定中的意义

骨代谢在氟的作用下发生异常而导致氟骨症,而尿羟脯氨酸排出量能基本反映骨代谢的变化[1]。根据以往实验研究证实硒、钼、硼等微量元素可以减轻氟骨症的骨损害[2],因此我们通过对尿氟、尿HYP的测定,比较硒、钼、硼对氟的拮抗作用的差别,来观察尿氟、尿HYP作为评价指标的意义。     

钙剂和硒对饮茶型氟中毒小鼠肝、肾病理形态学改变的影响

目的研究钙剂和硒对饮茶型氟中毒小鼠肝、肾病理形态改变的影响,从而为防治饮茶型氟中毒提供科学依据。方法以常规饲料饲养小鼠,并给予含氟量为100mg/L的砖茶水,为期3个月,建立饮茶型氟中毒小鼠的病理模型;去除自然死亡的小鼠,按体质量随机分成4组:对照组,砖茶组,钙剂组,硒组。对照组饮用自来水,砖茶组饮用含氟量为100mg/L的砖茶浸出液,钙剂组饮用2mg/L的钙剂和砖茶浸出液,硒组饮用2mg/L的亚硒酸钠溶液和砖茶浸出液,一个月后处理实验动物,通过组织病理学观察钙剂和硒对饮茶型氟中毒小鼠肝、肾病理形态学改变的影响。结果硒组小鼠肝、肾细胞组织的后继损伤较轻,而钙剂组肝,肾病理损伤较重。结论硒对饮茶型氟中毒小鼠的肝、肾细胞的后继损伤有一定的保护作用,但不能明显减轻已造成的小鼠肝、肾病理形态的改变,证明和在一定程度上可拮抗氟的毒性作用,减轻氟中毒病情,减缓氟中毒的进一步的发展。而钙剂加重氟中毒的发展。     

短时吸入安氟醚、异氟醚对大鼠边缘系统c-fos基因表达的影响

目的　探讨短时吸入安氟醚、异氟醚麻醉对大鼠边缘系统c fos原癌基因表达的影响。方法　 18只SD♂大鼠随机均分为 3组 :对照组、安氟醚组、异氟醚组 ,每组 6只。用c fos免疫组化技术观察短时吸入 2 %安氟醚或 2 %异氟醚对大鼠边缘系统c fos原癌基因的表达的影响。结果　安氟醚、异氟醚两组大鼠的杏仁中介核、杏仁内侧核、杏仁基外侧核、外侧僵核、正中视前核、外侧隔核、终纹床核、隔下丘脑核、下丘脑室周核、视上核等 10个核团Fos免疫样 (fos likeimmunoreactive ,FLI)阳性神经元数目均增加。除安氟醚组杏仁内侧核和视上核增加不明显 (P >0 0 5)外 ,差异均有统计学意义 (P <0 0 1)。结论　边缘系统中杏仁中介核、杏仁基外侧核、外侧僵核、正中视前核、外侧隔核、终纹床核、隔下丘脑核、下丘脑室周核等 8个核团可能参与了安氟醚、异氟醚的麻醉诱导过程 ,杏仁内侧核和视上核可能还参与了异氟醚的麻醉诱导过程     

来氟米特对阿霉素肾病大鼠尿、肾脏VEGF表达的影响

目的:探讨来氟米特对阿霉素肾病大鼠尿、肾脏血管内皮生长因子(VEGF)表达的影响。方法:将56只清洁级雄性Wistar大鼠随机分为正常对照组(生理盐水组)、肾病组(阿霉素组)、治疗组(来氟米特组)。建立阿霉素肾病大鼠模型,各组分别于第2周、4周、6周处死大鼠,取尿、肾脏,用ELISA方法检测并做相关分析。结果:肾病组在第2周、4周、6周时VEGF在尿、肾组织中的含量均显著高于正常对照组(P<0.01);且均与24h尿蛋白量呈正相关(r=0.81;0.63;P<0.01);来氟米特(LEF)干预组上述指标均显著低于肾病组,差异有统计学意义(P<0.01)。结论:来氟米特对阿霉素肾病大鼠肾脏损害有保护作用,其机制可能是通过降低VEGF表达而实现。     

氟他胺与2-羟基氟他胺对大鼠前列腺增生的抑制作用(英文)

目的 :研究氟他胺与 2 羟基氟他胺对诱导的前列腺增生大鼠前列腺萎缩和细胞凋亡的作用。方法 :SD大鼠去势 ,皮下注射丙酸睾丸素诱导前列腺增生。前列腺增生大鼠随机分成以下 5组 :对照组、氟他胺组 5 0与 1 0 0mg·kg-1,2 羟基氟他胺组2 5与 5 0mg·kg-1,用药时间为 1 0d。比较前列腺各侧叶湿重 ,以HE染色及TUNEL染色法观察细胞凋亡并计算凋亡发生率。结果 :氟他胺及 2 羟基氟他胺可明显降低前列腺增生大鼠前列腺各侧叶湿重 ,差异有显著意义 ,并可观察到明显的凋亡细胞。结论 :氟他胺与 2 羟基氟他胺可诱导前列腺增生大鼠的前列腺萎缩和细胞凋亡     

燃煤型氟中毒对大鼠睾丸超微结构的影响

目的研究燃煤型氟中毒对SD大鼠睾丸超微结构的影响。方法以SD大鼠为研究对象,按体质量均衡随机分为7组:对照组、高氟组、中氟组、低氟组、高氟加营养组、中氟加营养组、低氟加营养组。各染毒组喂饲含不同比例的燃煤型氟中毒病区煤烘玉米的饲料,复制燃煤型氟中毒动物模型。分3批(90 d,120 d,180 d)以股动脉放血法处死动物,查看氟斑牙,测尿氟。常规制作睾丸超薄切片,用透射电镜观察睾丸超微结构的变化。结果 (1)建成氟中毒动物模型,90 d各染毒组均出现氟中毒表现,对照组正常。中毒程度随氟剂量增加和染毒时间延长而加重;氟剂量相同时,营养好,中毒程度轻。(2)对照组结构正常。染毒组曲精小管内各级生精细胞生成减少,精子数量减少,各级生精细胞、睾丸间质细胞、肌样细胞、支持细胞的超微结构均有不同程度的病理变化。随氟剂量增加和染毒时间延长,病变加重。相同染氟剂量和加营养组比较,加营养组病变程度减轻。结论 (1)燃煤型氟中毒对SD大鼠睾丸组织超微结构有明显的损伤作用,随氟剂量和染毒时间延长,病变加重。(2)降低摄氟量及改善营养状况,可改善氟中毒对大鼠睾丸超微结构的损伤。     

慢性氟中毒大鼠软骨酶活性的实验观察

近年来 ,对氟中毒大鼠软骨酶活性状态的研究取得了一定进展 ,文献报道 ,在短期内形成氟中毒的大鼠 ,其软骨酶活性呈明显活跃状态[1] ;而对慢性氟中毒状态下大鼠软骨酶活性的观察 ,更具研究价值。本实验通过饮用高氟水致大鼠呈慢性氟中毒状态 ,观察其软骨酶活性变化。1　材料及方法1 1　动物分组及慢性氟中毒大鼠模型建立　Ｗｉｓｒａｒ健康大鼠共 2 8只 ,体重 175～ 2 15ｇ ,随机分为两组雌雄各半 ,分笼喂养 ,按文献 [1]方法 ,实验组大鼠自由饮用 10 0ｍｇ/ＬＮａＦ水致慢性氟中毒 ,对照组大鼠饮用自来水 (含氟 0 7ｍｇ/Ｌ)。两组大鼠同食…     

Caspase-3及Cleaved-Caspase-3在氟中毒大鼠肝脏中表达

目的 探讨氟中毒大鼠肝脏组织中Caspase-3及Cleaved-Caspase-3的表达情况.方法 选用36只健康SD大鼠分为对照组、低氟组、高氟组(饮用含氟量分别为＜1 mg/L、5mg/L及50 mg/L的自来水),每组12只(雌雄各半).饲养6个月后,股动脉放血处死,氟离子电极法检测大鼠尿氟含量;自动血生化分析仪检测大鼠肝功能;免疫组织化学法和蛋白印记(Western blot)法检测Caspase3及Cleaved-Caspase-3蛋白表达水平.结果 低氟组、高氟组大鼠尿氟[(1.85±0.13)、(2.23±o.10) mg/L均高于对照组[(1.63±o.11) mg/L] (P＜0.05);低、高氟组大鼠血清谷丙转氨酶及谷草转氨酶活性[(48.66±5.55)、(68.17±8.39)U/L及(142.57±16.21)、(165.89±28.26) U/L]均高于对照组[(38.49±2.98)、(117.98±9.88) U/L](P＜0.05);高过剂量氟组Caspase-3及Cleaved-Caspase-3蛋白表达[(98.08±13.08)、(106.33±9.14)]明显高于对照组[(53.92±6.36)、(59.78±7.54)l(P＜0.05).结论 氟可促进Caspase-3及Cleaved-Caspase3蛋白的表达,其可能参与慢性氟中毒所致肝脏损伤发病过程.     

氟西汀对慢性应激大鼠前额叶谷氨酸转运体GLT-1表达的影响

目的研究氟西汀对慢性应激大鼠前额叶谷氨酸转运体1(GLT-1)的影响,进一步探讨氟西汀抗抑郁作用可能的分子机制。方法正常SD大鼠60只,随机分为对照组、慢性不可预见性应激(CUS)组和氟西汀组。对CUS组和氟西汀组大鼠进行CUS应激后,氟西汀组给予氟西汀治疗,对照组和CUS组给予生理盐水。实验结束后进行糖水偏好和旷场行为测试,并使用免疫组织化学法和蛋白印迹分析检测大鼠前额叶GLT-1的表达水平。结果 (1)行为学测试结果显示,CUS组大鼠糖水偏好、总行程、平均移动速度及直立次数均低于对照组(P<0.01);氟西汀组上述指标均高于CUS组(P<0.01)。(2)免疫组织化学法分析显示,CUS组与对照组比较,大鼠前额叶GLT-1表达下降(P<0.01);经氟西汀治疗后,大鼠前额叶GLT-1表达比CUS组明显升高(P<0.01)。(3)蛋白印迹分析显示,CUS组与对照组比较,大鼠前额叶GLT-1表达下降(P<0.01);经氟西汀治疗后,大鼠前额叶GLT-1表达比CUS明显升高(P<0.01)。结论慢性应激下调大鼠前额叶GLT-1表达水平,而氟西汀上调GLT-1表达水平,GLT-1表达增加可能是氟西汀抗抑郁作用的分子机制之一。     

燃煤型氟中毒大鼠血清睾酮水平的变化及机制的初步研究

目的:研究燃煤型氟中毒大鼠血清睾酮的变化及可能的机制.方法:以SD大鼠为研究对象,按体质量均衡随机分为对照组、低氟组、中氟组、高氟组4组.各染毒组喂饲含不同比例的燃煤型氟中毒病区煤烘玉米的饲料,复制燃煤型氟中毒动物模型.180d以股动脉放血法处死动物.查看氟斑牙,测尿氟、血清睾酮水平,常规制成肾上腺和睾丸HE染色病理切...     

氧化应激在燃煤污染型氟中毒大鼠中的作用

目的研究氧化应激在燃煤污染型氟中毒大鼠中的作用。方法选择SD大鼠随机分2组（每组11只，雌雄各半），设对照组、染氟组。染氟组以氟中毒病区煤烘玉米为主要饲料，复制氟中毒动物模型，检查氟斑牙、尿氟浓度及血清、肝、肾、脑组织中丙二醛（MDA）含量、超氧化物歧化酶（SOD）及谷胱甘肽还原酶（GR）活性，及血清中反映肝、肾功能的指标。结果染氟组大鼠血清、肝、肾、脑组织中MDA含量升高，SOD和GR活性明显降低（P〈0．05或P〈0．01）。同时大鼠肝、肾功能已有一定的改变。结论氟中毒大鼠机体内氧化系统与抗氧化系统失衡，氧化应激引起的氧化损伤作用在氟致大鼠肝、肾毒性中起着重要的作用。     

Prevention of brick tea fluorosis in rats with low-fluoride brick tea on laboratory observation.

To test whether low-fluoride brick tea can prevent the occurrence of fluorosis, rats had access only to a specially prepared low-fluoride brick tea for 1 year. The daily fluoride intake, fluoride metabolism, tissue distribution and development of tooth fluorosis were observed at 4-monthly intervals, at the end of months 4, 8 and 12, respectively. Rats drinking ordinary brick tea (F- 503.5 mg/kg) served as control. The daily intake of fluoride in the ordinary brick tea group was 0.3 mg, and this group developed dental fluorosis characterized as brown and white horizontal marks at the end of month 8, and white chalky dental fluorosis developed at the end of month 12. The total incidence was 75%. In contrast, the daily fluoride intake of the low-fluoride brick tea (F- 210 mg/kg) group was 0.19 mg, and this group did not develop any signs of dental fluorosis. Fluoride distribution was mainly retained in the bone tissue, and about half of the absorbed fluoride was excreted via urine and feces. The results suggest that this low-fluoride brick tea did not induce fluorosis in rats and can be used as an effective control measure for humans.     

Protein and mRNA expression of Shh,Smo and Gli1 and inhibition by cyclopamine in hepatocytes of rats with chronic fluorosis

In order to investigate the Sonic hedgehog (Shh) signaling pathway and the effect of cyclopamine in rat hepatocytes with chronic fluorosis, 48 Wistar rats were randomly divided into 4 groups. The control group was provided with tap water in which the fluorine concentration was <1 mg/L, while the remaining three groups were provided with water containing sodium fluoride (NaF) at a concentration of 50 mg/L. After 6 months, the blocking and blocking control groups were injected intraperitoneally once every 2 days for 6 days with 10 mg/kg cyclopamine or dimethyl sulfoxide, respectively. The urinary and skeletal fluoride contents were determined by the ion selective electrode method. Levels of aspartate transaminase (AST), alanine transaminase (ALT), total protein (TP) and albumin (Alb) in the serum were determined by using autobiochemical machine. Histological changes in liver tissue were evaluated with Hematoxylin & Eeosin (H&E) staining using light microscopy. The protein and mRNA expression of Shh, Smo and Gli1 in hepatocytes of experimental animals was determined by immunohistochemistry (IHC), Western blotting (Wb) and Real-time quantitative PCR (RT-qPCR). Fluoride content of the urine and bone was increased in the fluorosis and blocking groups compared to those in the control group (P < 0.05), while fluoride content in the blocking group was decreased compared to the fluorosis and blocking control groups (P < 0.05). The expression of Shh, Smo and Gli1 at the mRNA and protein levels was significantly increased in hepatocytes from the fluorosis and blocking control groups compared with the control group, and expression in the blocking group was lower than that of the fluorosis and blocking control groups. The difference between any two groups was considered to be statistically significant (P < 0.05). Taken together, our study indicates that the expression of Shh, Smo and Gli1 at the protein and mRNA level in hepatocytes of rats with chronic fluorosis can be increased by fluoride and may be inhibited by cyclopamine and that the Shh signaling pathway plays an important role in the liver pathogenesis caused by fluorosis.     

燃煤污染型氟中毒特重病区病情调查分析

目的了解我省地氟病特重病区的病情流行及变化状况,研究特重病区村形成的相关流行因素。方法按照GB16396-1996、WS192-1999和Dean氏分级标准,在调查村对3岁以上人群分别进行氟骨症和氟斑牙检查;在两个调查采集8岁以上人群一次性尿样检测尿氟含量;文献查询特重病区村历史病情资料。结果荷花、联合2个特重病区村8～12岁儿童氟斑牙检出率和缺损型检出率分别为94.3%、82.7%、58.1%和63.7%,均显著高于对照村。两个特重病区村中度以上氟骨症临床症状体征阳性检出率为72.6%和69.7%,氟骨症X线阳性确诊率为79.3%和80%,均显著高于对照村,特重病区村和对照村16岁以下人群未检出氟骨症阳性患者。荷花和联合村人群尿氟几何均数分别为3.2mg/L和2.3mg/L,较上世纪70-80年代显著降低。结论横向比较,现阶段两个特重病区村的氟中毒病情较对照村重,与自身历史资料纵向比较,两个特重病区村的氟中毒流行现况较上世纪70-80年代明显减轻。     

氟斑牙儿童甲状腺激素异常与DIO1基因多态性的关系

目的　分析氟斑牙儿童甲状腺激素异常情况及与Ⅰ型脱碘酶（DIO1）基因多态性的关系。方法　2018年6月—2019年6月,在天津市历史水氟区和非水氟区共随机抽取169名7~12岁儿童,检测儿童氟斑牙水平。其中正常儿童（正常组）79名,氟斑牙儿童（氟斑牙组）90名。采集尿样,利用砷铈催化分光光度方法测定尿碘水平。采集血样,化学发光法检测促甲状腺激素（TSH）、游离三碘甲状腺原氨酸（FT3）和游离甲状腺素（FT4）,采用Sequenom SNP分型检测实验测定DIO1中rs2294512位点的多态性,并进行问卷调查。根据DIO1 rs2294512位点的基因型分层后进行多因素Logistic回归分析,研究DIO1基因多态性在氟斑牙与甲状腺激素异常中的作用。结果　相对于正常组,氟斑牙组FT3水平较高,FT4水平较低（P＜0.05）。氟斑牙组FT3过高率达40.0%,高于正常组的21.5%,FT4过高率为3.3%,低于正常组的12.7%（P＜0.05）。DIO1基因AA基因型儿童中,患氟斑牙者FT3较高（OR=6.357,95%CI：1.808~22.347,P=0.004）。结论　DIO1基因rs2294512位点为AA基因型的氟斑牙儿童FT3水平更易升高。     

The influence of chronic fluorosis on mitochondrial dynamics morphology and distribution in cortical neurons of the rat brain

The present study was designed to evaluate the effects of chronic fluorosis on the dynamics (including fusion and fission proteins), fragmentation, and distribution of mitochondria in the cortical neurons of the rat brain in an attempt to elucidate molecular mechanisms underlying the brain damage associated with excess accumulation of fluoride. Sixty Sprague–Dawley rats were divided randomly into three groups of 20 each, that is, the untreated control group (drinking water naturally containing <0.5 mg fluoride/l, NaF), the low-fluoride group (whose drinking water was supplemented with 10 mg fluoride/l) and the high-fluoride group (50 mg fluoride/l). After 6 months of exposure, the expression of mitofusin-1 (Mfn1), fission-1 (Fis1), and dynamin-related protein-1 (Drp1) at both the protein and mRNA levels were detected by Western blotting, immunohistochemistry, and real-time PCR, respectively. Moreover, mitochondrial morphology and distribution in neurons were observed by transmission electron or fluorescence microscopy. In the cortices of the brains of rats with chronic fluorosis, the level of Mfn1 protein was clearly reduced, whereas the levels of Fis1 and Drp1 were elevated. The alternations of expression of the mRNAs encoding all three of these proteins were almost the same as the corresponding changes at the protein levels. The mitochondria were fragmented and the redistributed away from the axons of the cortical neurons. These findings indicate that chronic fluorosis induces abnormal mitochondrial dynamics, which might in turn result in a high level of oxidative stress.     

Antioxidant defense system and lipid peroxidation in patients with skeletal fluorosis and in fluoride-intoxicated rabbits.

Fluorosis is a serious public health problem in many parts of the world where drinking water contains more than 1 ppm of fluoride. The main manifestations of skeletal fluorosis are crippling bone deformities, spinal compressions, and restricted movements of joints. Although fluorosis is irreversible, it could be prevented by appropriate and timely intervention through understanding the process at biochemical and molecular levels. As in the case of many chronic degenerative diseases, increased production of reactive oxygen species (ROS) and lipid peroxidation has been considered to play an important role, even in the pathogenesis of chronic fluoride toxicity. However, there is inconclusive proof for an altered oxidative stress and antioxidant balance in fluorosis, and the existing data are not only conflicting but also contradictory. In the present communication we have evaluated the antioxidant defense system (both enzymatic and nonenzymatic) and lipid peroxidation in both humans from an endemic fluorosis area (5 ppm fluoride in the drinking water) and in rabbits receiving water with 150 ppm of fluoride for six months. There was no significant difference in lipid peroxidation, glutathione, and vitamin C in the blood of human fluorotic patients and fluoride-intoxicated rabbits as compared to respective controls. Neither were there any changes in the activities of catalase, superoxide dismutase, glutathione peroxidase, or glutathione S-transferase in the blood due to fluoride intoxication (of rabbits) or fluorosis in humans. The results together do not subscribe to oxidative stress theory in fluorosis. Thus, in the absence of clear proof of oxidative damage and to counter toxic effects of fluoride through supplementation of antioxidants, extensive investigations are needed to conclusively prove the role of oxidative stress in skeletal fluorosis.