氟中毒大鼠的垂体催乳素分泌

分别用腹腔注射氟化钠和喂饲含氟水的方法制造了大鼠亚急性和慢性氟中毒模型。以放免法测定了氟中毒情况下血清及垂体的催乳素含量。得到如下结果:①慢性氟中毒雌性大鼠血清催乳素水平降低,且呈剂量效应关系,垂体催乳素含量则升高。雄性大鼠血清催乳素水平无显著变化,但垂体催乳素含量增高,且呈现剂量—效应关系。②亚急性氟中毒大鼠血清催乳素水平显著升高,但垂体催乳素含量无显著变化。     

刺梨汁拮抗慢性氟中毒的实验观察

用含氟３２０ｍｇ／ｋｇ饲料和含维生素Ｃ６００ｍｇ／１００ｍｌ刺梨汁饮不饲养Ｗｉｓｔａｒ大鼠６个月，探讨刺梨汁对慢性氟中毒的影响及其机理。结果发现刺梨汁具有明显改善慢性氟中毒的一般状况，减少氟斑牙的形成，增加氟中毒大鼠的体重，促进尿氟排泄，降低血清和骨氟含量，提高血清维生素Ｃ含量，保护胶原组织，使尿羟脯氨酸含量降低，通过提高血清维生素Ｅ和ＧＳＨ含量，增强血ＧＳＨ－Ｐｘ和ＳＯＤ活性而抑制氟中毒引起的脂     

过量氟对实验大鼠血清一氧化氮含量及骨发育的影响

目的　为了探讨一氧化氮与氟性骨关节病骨软骨损伤的关系，进行了过量氟对实验性大鼠血清 Ｎ Ｏ 含量及骨发育影响的研究。方法　测定了３种不同剂量过量氟实验性大鼠血清的 Ｎ Ｏ 含量，对 Ｎ Ｏ 含量和大鼠胫骨纵径、横径进行了相关分析。结果　氟中毒大鼠血清 Ｎ Ｏ 含量明显升高（ Ｐ ＜ ０．０５），且依氟剂量的增加而递增；血清中 Ｎ Ｏ 含量与胫骨纵径、横径呈负相关。结论　过量氟致实验性大鼠血清 Ｎ Ｏ 含量升高，依染氟剂量增加而增加；过量氟影响大鼠骨发育。     

氟中毒对雄鼠垂体—性腺轴功能的影响

分别用腹腔注射氟化钠和喂饲含氟水的方法制造了雄鼠亚急性和慢性氟中毒模型,观察了对大鼠垂体—性腺轴功能的影响。得到如下结果:亚急性氟中毒大鼠前列腺、睾丸和垂体的相对重量均无显著变化,血清睾酮水平降低,LH 水平显著升高,但垂体 LH 含量无显著变化;慢性氟中毒大鼠睾丸和垂体的相对重量均无显著变化,但前列腺的相对重量有随饮水氟浓度的升高而降低的趋势,血清睾酮水平降低,且与饮水氟浓度呈剂量—效应关系,血清 LH 无明显变化,但垂体 LH 含量有所降低。     

不同氟中毒动物模型肾脏功能与离子代谢的变化

目的：观察不同氟中毒动物模型肾脏功能与离子代谢的变化。方法;经饮水投氟复制氟中毒模型。采用全自动生化分析仪检测血清内反映肾功能指标和相关离子代谢,应用放射免疫技术测定血,尿中的β2－MG含量。结果：氟中毒家兔和大鼠的BUN,Cr,UA变化不明显,β2－MG投氟组与对照组比较无明显差异。氟中毒家兔和大鼠离子代谢紊乱,并且以Ca^2 代谢紊乱明显。结论：高氟剂量或在伴有钙缺乏的情况下,血清内离子代谢紊乱明显,尤以Ca^2 表现显,但氟中毒时肾功能损害不明显。     

维生素C对实验性氟中毒大鼠血清氟及骨氟含量的影响

为研究维生素Ｃ对氟中毒的影响，以Ｗｉｓｔａｒ大鼠７２只随机分为３组，第１组为阴性对照组：２４只，自由饮用自来水（氟含量＜１ｍｇ／Ｌ）；第２组为氟中毒＋维生素Ｃ组：２４只．自由饮用５０ｍｇ／Ｌ含氟水１２０ｄ后，加用ＶＣ１ｇ／ｋｇ·ｄ灌胃治疗；第３组为氟中毒后脱离氟源＋维生素Ｃ组：２４只，自由饮用５０ｍｇ／Ｌ含氟水１２０ｄ，然后去除含氟水，自由饮用自来水，同时用ＶＣ１ｇ／ｋｇ·ｄ灌胃治疗。实验第１２０ｄ及ＶＣ治疗第１周、３周、６周末分别检查体重、血清氟及骨氟含量。结果显示；实验第１２Ｏｄ，氟中毒大鼠血清氟及骨氟含量均明显高于阴性对照组，差异有显著性（Ｐ＜０．０５）。氟中毒＋ＶＣ组第１周、３周、６周后，血清氟明显降低，体重明显增加，与氟中毒大鼠相比，差异有显著性（Ｐ＜０．０５）。脱离氟源＋ＶＣ治疗第１、３、６周后，血清氟明显降低，体重明显增加，第３周、６周后，骨氟有明显降低，与氟中毒大鼠相比，差异均有显著性（Ｐ＜０．０５）。实验结果表明；ＶＣ具有明显降低血清氟、骨氟及增加体重的作用。     

不同钙营养条件下氟中毒大鼠血清甲状旁腺激素的变化

目的动态观察不同钙营养条件下过量氟对大鼠血清甲状旁腺激素(PTH)的影响。方法以SD雄性大鼠为实验对象,采用3×2×3析因设计,按体质量随机分为6组:高钙对照组、高钙氟化钠组、常钙对照组、常钙氟化钠组、低钙对照组、低钙氟化钠组。分别饲以含钙量不同的合成饲料,各对照组饮用去离子水,各氟化钠组饮用含氟100 mg／L的去离子水。每8周处死一批大鼠,观察氟斑牙发生情况,用氟离子选择电极法测定血清氟、骨氟,用比色法测定血清钙,用放射免疫方法检测血清PTH水平。结果不同钙营养条件下加氟组大鼠均出现氟中毒;随染氟时间延长,不同钙营养条件下氟中毒大鼠的血清PTH活性升高,尤其高钙和低钙氟中毒大鼠血清PTH活性比常钙对照组显著升高(P<0．05或0．01);在实验初期常钙和高钙氟中毒大鼠血清钙低于其对照组(P<0．01),后期高钙氟中毒大鼠血清钙明显低于其对照组(P<0．05)。结论长期摄入过量氟可使机体血清PTH水平代偿性增高以维持血钙保持在正常范围内;长期摄入过量钙可减少氟在体内的蓄积。     

慢性氟中毒大鼠血清中OPG、RANKL、IL-1β和TNFα的变化

目的探讨氟中毒大鼠血清中OPG、RANKL、IL-1β和TNFα的变化及它们之间的关系。方法通过低钙与含氟饮食建立氟中毒大鼠模型,采用Elisa法测定氟中毒大鼠血清中OPG、RANKL、IL-1β和TNFα表达。结果氟摄入可以提高血清OPG、IL-1β和TNFα水平;低钙饮食提高血清OPG水平,不影响IL-1β和TNFα水平;低钙与氟摄入协同能提高血清RANKL水平。结论慢性氟中毒大鼠血清中OPG、RANKL、IL-1β和TNFα发生了变化;OPG升高是主要的,可以反应机体内破骨或协同破骨因素总的变化程度。     

慢性氟中毒对大鼠肝、肾组织中Nrf2基因表达影响

目的建立大鼠慢性氟中毒模型,观察氟中毒对大鼠肝脏、肾脏抗氧化能力的影响。方法 40只Wistar大鼠随机分为4组,分别为空白对照组、低剂量染氟组、中剂量染氟组、高剂量染氟组。8周后麻醉处死,腹主动脉取血,检测血清氧化应激水平;RT-PCR检测肝脏和肾脏Nrf2、HO-1、Gpx-1的mRNA表达。结果慢性氟中毒大鼠血清氟、GSH-px、SOD水平降低、MDA水平升高。RT-PCR检测结果表明,氟中毒大鼠肝、肾组织Nrf2、HO-1 mRNA表达升高,Gpx-1 mRNA表达降低。结论慢性氟中毒引起大鼠肝、肾组织氧化应激,其可能是与氟中毒调控Nrf2及其下游HO-1、Gpx-1表达有关。     

慢性氟中毒对大鼠胰岛机能与形态的影响

为观察慢性氟中毒对大鼠胰岛的影响，选用ｗｉｓｔａｒ大白鼠饮用１００ｍｇ／Ｌ高氟水一年，复制慢笥氟中毒动物模型。结果显示；氟中毒大鼠血清胰素含量较对照组显著升高，胰高糖素水平略有下降；胰岛组织化学染色的形态学定理分析研究也证实，胰岛面积显著增加，胰岛素样反应阳笥产物面积也有一定程度的增加，同时，胰岛形状因子显著变小。     

永嘉县氟中毒未成年人血清碱性磷酸酶水平的变化情况分析

目的探讨永嘉县氟中毒未成年人血清碱性磷酸酶水平的变化情况。方法选择2012年4月至2013年4月永嘉县入院检查诊断为氟中毒的未成年人共67例作为氟中毒组,按照1∶1对照方案选择同年龄、同性别的入院体检的健康儿童67例作为对照组,比较2组受试者血清碱性磷酸酶的水平。结果不同年龄阶段氟中毒儿童血清碱性磷酸酶水平均显著高于对照组儿童（P〈0.05）;将ALP〉500 U/L作为异常,本研究共检出异常者8例,其中氟中毒组检出异常7例,异常率为10.45%,对照组检出异常1例,检出异常率为1.49%,2组比较,差异具有统计学意义（P〈0.05）。结论氟中毒儿童其血清碱性磷酸酶活性有所增加,血清碱性磷酸酶升高对儿童氟中毒所致骨损伤具有着重要的意义。     

氟中毒大鼠骨骼X线动态观察及硒的影响

目的 观察氟中毒大鼠骨Ｘ线改变及硒的影响。方法 ２个组Ｗｉｓｔａｒ大鼠饮１．５８和２．６３ｍｍｏｌ／Ｌ氟水；２个组鼠饮氟水加饲２．０ｍｇ／ｋｇ硒饲料。每２个月用钼靶Ｘ线摄骨片共计６次。实验１４个月时测血、尿、骨氟。结果 氟中毒大鼠血、尿骨氟升高。骨Ｘ改变以骨盆骨结构异常出现最早，其次为腰椎、尾骨；前、后肢改变晚且较少；前肢显现骨间膜骨化，且晚于骨结构改变。实验８个月发性早期氟骨症征象。氟加硒大鼠血     

高海拔饮茶型氟中毒大鼠血清钙磷水平及碱性磷酸酶活性观察

目的探讨高海拔地区饮茶型氟中毒的发病机制：方法动态观察高海拔地区饮茶型氟中毒大鼠血清碱性磷酸酶(ALP)活性、钙(Ca)、磷(P)水平。结果砖茶水组ALP活性呈逐渐下降趋势．但仍高于对照组；砖茶水组血清Ca在30d时低于对照组，以后逐渐回升接近对照组水平；砖茶水组血清P在30d时高于对照组，以后逐渐下降接近对照组水平。结论高海拔饮茶型氟中毒可能存在较为复杂的发病机制。     

Corticosterone concentrations in the serum and milk of lactating rats: parallel changes after induced stress

Transfer of corticosterone from serum to milk was studied in lactating rats after ether and pentobarbital anesthesia. Two minutes after the onset of anesthesia stress, total serum and milk corticosterone concentrations were not significantly different. By 30 min, corticosterone concentrations in serum increased to a peak and plateaued at about this level during the 2-h experimental period, while concentrations in milk reached a maximal plateau only at 50 min poststress. The peak corticosterone concentrations in serum and milk were 76 +/- 6 and 36 +/- 4 micrograms/dl, respectively. By centrifugal ultrafiltration dialysis, the percentages of free corticosterone in serum and milk were not significantly different at the maximal concentrations; thus, free corticosterone in serum was about 200% of that in milk. In contrast, anesthesia stress had no effect on serum and milk corticosteroid-binding globulin concentrations; the serum to milk ratio was approximately 10:1. No accumulation of corticosterone in milk was observed after repeated ether stress. Decreases in milk corticosterone levels after recovery from ether stress paralleled that of its serum counterpart. These results indicate that corticosterone concentrations in milk increase rapidly after ether stress, but are limited to a level significantly lower than that in serum. The possible effects of corticosterone in milk on the development of infant rats remains to be defined.     

地方性氟中毒患者多项检验指标的测定及分析

目的　探索地方性氟中毒有意义的检测诊断指标。方法　选轻、中、重不同病情的地氟病病人600名,进行血、尿常规和生化等21项检查。血、尿氟采用离子选择电极法,生化及酶类采用RABA生化自动分析仪检验;T     

Uptake of corticosterone by the perfused rat liver

The mechanism of hepatic uptake of corticosterone from plasma was investigated in the isolated perfused rat liver using an indicator-dilution method. The hepatic influx rate constant for free corticosterone was determined from measurements of the rate of hepatic uptake of corticosterone from protein-free buffer. The rate of hepatic uptake of corticosterone from pooled normal rat serum was then measured. A general model of hormone transport that does not assume that hormone-protein complexes remain at equilibrium during transit through the hepatic sinusoids was used to ask whether this observed rate of uptake could be accounted for by a pool of free corticosterone that turns over very rapidly. Parameter values used in this analysis included the measured concentrations of albumin and corticosteroid-binding globulin in the serum, literature values for the rate constants describing the interactions of corticosterone with these proteins, and the value of the hepatic influx rate constant for free corticosterone determined in the present study. The rate of hepatic uptake of corticosterone from rat serum that we observed was very similar to the rate of uptake predicted by this model to occur via the pool of free corticosterone.     

不同营养因素对大鼠骨软化性氟骨症骨生物力学的影响

用大白鼠复制骨软化性的有症动物模型，并通过饲料分别补加钙，维生素Ｃ、鱼肝油及酪蛋白四种成分，观察其对股骨生物力学的影响。     

氟对大鼠骨组织3-磷酸肌醇激酶和蛋白激酶B1表达的影响

目的 观察慢性氟中毒对大鼠骨组织中3-磷酸肌醇激酶(PI3K)、蛋白激酶B1(Akt1)蛋白和mRNA表达的影响,探讨PI3K/Akt信号通路在氟骨症发病机制中的作用.方法 将36只SD大鼠按性别和体质量随机分为3组:对照组、低氟组、高氟组,每组12只.对照组自由饮用自来水(含氟量<0.5 mg/L),低、高氟组大鼠分别饮用氟化钠(NaF)配制的含氟量为5.0、50.0 mg/L的自来水.实验6个月后处死大鼠,收集血清,用酶联免疫吸附测定(ELISA)法检测骨钙素(BGP)、组织蛋白酶K(Cath-K).取大鼠股骨下段,用免疫组织化学方法和实时荧光定量PCR法检测骨组织中PI3K、Akt1蛋白和mRNA的表达.结果 各组大鼠血清BGP、Cath-K 水平比较,差异有统计学意义(F值分别为73.45、39.36,P均<0.05).与对照组[(0.15±0.03)μg/L、(18.32±2.27)pmol/L]比较,低、高氟组血清BGP[(1.99±0.62)、(2.38±0.16)μg/L]、Cath-K[(89.07±19.66)、(110.16±9.81)pmol/L]明显升高(P均<0.05),且高氟组明显高于低氟组(P均<0.05).各组大鼠骨组织PI3K、Akt1蛋白和mRNA表达水平比较,差异有统计学意义(F值分别为178.16、118.08,38.81、52.31,P均<0.05).与对照组(181.55±4.24、188.46±2.18,3.84±1.69、4.33±0.89)比较,低、高氟组大鼠骨组织PI3K(171.66±2.85、154.12±4.15,11.31±4.18、20.54±6.68)、Akt1蛋白和mRNA表达(177.47±3.16、156.42±3.18.12.52±3.13、19.43±5.36)明显增高(P均<0.05),且高氟组明显高于低氟组(P均<0.05).结论 血清BGP、Cath-K可作为慢性氟中毒骨病变的代谢指标.氟可导致大鼠骨组织中PI3K、Akt1蛋白和mRNA表达水平增高,PI3K/Akt 信号通路可能参与了氟引起的骨骼损伤机制.

Abstract：

Objective To observe the expression of phosphoinositide 3-kinase(PI3K) and protein kinase B1 (Akt1) in PI3K/Akt signaling pathway in rat bones with fluorosis, and to reveal the mechanisms of the skeletal fluorosis. Methods Thirty-six SD rats were randomly divided into 3 groups (control group, low-dose fluorosis group, high-dose fluorosis group) and 12 rats were in each group according to body weight. The rats were fed with different concentrations of fluoride (NaF) to establish fluorosis models. Controls were fed with tap water( < 0.5 mg/L), experimental animals in low- or high-dose groups were fed with water containing NaF 5.0,50.0 mg/L, respectively. Rats were sacrificed after 6 months of treating with fluoride and the serum was kept for testing the bone metabolic markers of none gla protein(BGP) and cathepsin K(Cath-K) by enzyme-linked immunosorbent assay(ELISA), the proteins and mRNA levels of PI3K and Akt1 in rat bones were detected by immunohistochemistry and real time PCR, respectively. Results Each group of serum BGP and Cath-k were compared, the difference was statistically significant(F = 73.45,39.36, all P < 0.05). The contents of BGP[(1.99 ± 0.62), (2.38 ± 0.16)μg/L] and Cath-K [(89.07 ± 19.66), (110.16 ± 9.81)pmol/L] in the low-and high-dose fluorosis groups were higher than those in the control group[(0.15 ± 0.03)μg/L,( 18.32 ± 2.27)pmol/L], and the high fluorosis group was obviously higher than the low fluorosis group (all P < 0.05). Each group of serum PI3K and Akt1 protein and mRNA were compared, the difference was statistically significant(F- 178.16,118.08,38.81,52.31, all P< 0.05). Compared to the control group (181.55 ± 4.24,188.46 ± 2.18,3.84 ± 1.69,4.33 ± 0.89), the protein and mRNA expressions of PI3K(171.66 ± 2.85,154.12 ± 4.15,11.31 ± 4.18,20.54 ± 6.68), Akt1(177.47 ± 3.16,156.42 ± 3.18,12.52 ± 3.13,19.43 ± 5.36) were higher in the low- and high-dose fluorosis groups (all P < 0.05), and the high fluorosis group was obviously higher than the low fluorosis group (all P < 0.05). Conclusions BGP and Cath-K contents could be used as bone metabolic indices in the endemic fluorosis disease. Fluoride can increase the expression of PI3K and Akt1 mRNA and protein in bone tissue of fluorosis rats, and PI3K/Akt1 signaling pathway may be involved in the pathogenesis of bone injury caused by fluoride.     

氟中毒大鼠心肌细胞电生理变化及硒的影响

为观察氟中毒大鼠心肌生理变化及硒对变化的影响，两组Ｗｉｓｔａｒ大鼠饮１．５８、２．６３ｍｍｏｌ／Ｌ高氟水，两组大鼠饮高水加饲２．０ｍｇ／ｋｇ硒饲料。实验进行４个月、８个月时服硒鼠尿硒、氟升高；８个月时血硒上升，血氟下降。心民生理参数显示氟中毒大鼠ＲＰ、ＡＰＡ、Ｖｍａｘ降低，ＡＰＤ５０、ＡＰＤ９０缩短。投硒则使ＲＰ、ＡＰＡ、Ａｍａｘ程度不同 的恢复，ＡＰＤ５０、ＡＰＤ９０达到对照组水平。表明氟中毒大