铅与氟联合作用的急性毒性实验研究

雄性SD大鼠分为四组:Ⅰ(A1),Ⅱ(F),Ⅲ(Al∶F=2.3∶1)和Ⅳ(Al∶F=1∶2.3)。一次经口灌胃后观察到,Ⅰ与Ⅲ组动物均出现铝中毒常见的眼眶出血症状,且死亡时间分布相似,表明高铝低氟摄入时有大量Al吸收产生铝毒性。应用改良等效线法评价联合作用性质,显示两种比例铝和氟均为拮抗作用,但Ⅲ组拮抗作用明显低于Ⅳ组,提示铝抗氟毒性作用并不随铝量增加而增强。     

燃煤型氟中毒大鼠血清骨保护素的变化

目的观察燃煤型氟中毒骨病变早期血清骨保护素(OPG)的变化。方法以SD大鼠为实验对象,随机分6组(组内雌雄各半):对照、低氟、中氟加营养、中氟、高氟加营养、高氟组。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。分两批以股动脉放血法处死动物,查看氟斑牙,测尿、骨、肾氟,骨密度(BMD),骨Ca、尿Ca,OPG。结果①建成氟中毒动物模型各染毒组均出现氟中毒,对照组正常。中毒严重程度随氟剂量增加而加重;氟剂量相同时,营养好中毒程度轻。②两批各染毒组大鼠血清OPG均升高(P<0.01),且随氟剂量升高而升高(P<0.05或0.01)。结论①血清OPG是反映燃煤型氟中毒骨病变的一个早期指标。②降低摄氟量及改善营养状况,可缓解氟中毒病情。     

骨软化性氟骨症发病机理研究

在偏食条件下给大白鼠饮水中加过量氟造成骨软化性氟骨症,引起一系列生化代谢改变。这些变化,在单纯低钙偏食时即已出现,投氟后则进一步加重。本文讨论了骨软化性氟骨症的发病机理,认为食饵低钙是骨软化性氟骨症发生、发展的基本条件;因血钙浓度下降而引发的趋钙激素的变化,使得骨软化愈演愈烈,改善居民钙营养状况,对防治地方性氟中毒具有重要意义。     

燃煤型软化型大鼠氟骨症骨代谢因子变化的探索

目的以氟病区煤烘玉米为主要饲料,复制燃煤型软化型氟骨症大鼠模型,通过对燃煤型软化型氟骨症大鼠血清骨代谢相关因子的研究,探讨氟骨症的发病机理。方法 210只断乳2周的SD大鼠,适应性喂养一周后,按体重均衡随机数字法将其分为对照组,低氟剂量组,中氟铝组,高氟铝组,高铝组,高氟组,高氟营养不良组,共7组,每组30只,组内雌雄各半。正常对照组食用正常饲料,其它组均食用不同配方饲料,复制燃煤型软化型氟骨症大鼠模型。2.大鼠骨骼病理学检测采用Goldner's Massion trichrome(三色法)染色、荧光观察与HE染色、光镜观察。3.采用放射免疫分析法(RIA)测定燃煤型软化型大鼠血清中BGP、CT、PHT、IGF-1浓度的变化。结果 1.复制燃煤型软化型氟骨症大鼠,经骨骼病理学检测,高氟铝组及高氟营养不良组呈骨软化型。2.染毒90 d时,高氟铝组和高氟营养不良组发生了骨软化,其血清BGP、PTH显著升高;高氟营养不良组血清CT比对照组升高,提示OC活性出现被抑制的倾向,抑制骨吸收作用;高氟铝和高氟营养不良组大鼠血清IGF-1均低于对照组,提示在营养不良和(或)干预铝的情况下,生长情况出现被抑制的现象。染毒165 d,高氟铝组和高氟营养不良组大鼠血清BGP、血清PTH、血清CT、血清OPG含量升高不显著;大鼠的血清IGF-1,继续保持低水平。结论燃煤型软化型氟骨症大鼠,骨代谢相关因子的影响作用并非引起单一因素的变化,而是多种因子的异常波动,它们之间还可能互相影响,尤其是软化型氟骨症大鼠的血清BGP和PTH的变化更明显。     

氟对大鼠血清蛋白~3H—亮氨酸掺入的影响

用35只 Wistar 大鼠,随机分为三组:Ⅰ对照组;Ⅱ饮水中含氟10ppm 组;Ⅲ饮水中含氟30ppm 组。饲养7个月后,Ⅱ、Ⅲ组大鼠尿氟浓度增高;Ⅲ组大鼠出现明显氟斑牙,体重降低;Ⅱ、Ⅲ组大鼠血清蛋白~3H—亮氨酸摻入值降低。表明摄入过量的氟可抑制血清蛋白的合成,并且在大鼠尚未出现典型的慢性氟中毒体征时,血清蛋白合成已明显降低。     

川芎嗪联合小剂量环孢素A对大鼠小肠同种异体移植急性排斥反应的影响

[目的]研究川芎嗪与小剂量环孢素A(CsA)对大鼠小肠同种异体移植急性排斥反应的影响。[方法]实验分5组,Ⅰ组:Wistar→SD小肠移植;Ⅱ组:Wistar→SD小肠移植加足量CsA;Ⅲ组:Wistar→SD小肠移植加小剂量CsA;Ⅳ组:Wistar→SD小肠移植加川芎嗪;Ⅴ组:Wistar→SD小肠移植加小剂量CsA和川芎嗪;术后3、57、d观察病理学改变,并用半定量RT-PCR方法检测白细胞介素2(IL-2)mRNA。[结果]病理改变:Ⅰ组术后3 d出现排斥反应,7 d最重;Ⅱ、Ⅴ组术后7 d部分出现轻度排斥反应;Ⅲ、Ⅳ组术后3 d出现轻度排斥反应,术后7 d重度排斥反应。Ⅰ组IL-2 mRNA术后明显增高,Ⅲ、Ⅴ组术后略升高,与Ⅰ组相比差异有统计学意义(P<0.01)。Ⅲ、Ⅳ组术后升高,与Ⅰ组比较差异无统计学意义(P>0.05)。[结论]川芎嗪联合小剂量CsA可抑制小肠移植急性排斥反应,其作用与大剂量CsA相当。     

大豆、硒粉、螺旋藻对高摄铝下氟中毒大鼠的干预效果

目的 观察高摄铝状态下氟中毒大鼠大豆、硒粉、螺旋藻的干预效果.方法 将断乳2周的SD纯系大鼠40只(雌雄各半)按体质量随机分为5组:对照组、高氟铝组、高氟铝加大豆组、高氟铝加硒组和高氟铝加螺旋藻组,每组8只.对照组食用非病区玉米加工的饲料(含氟5.20 mg/L,含铝6.80 mg/L),饮用自来水(含氟0.70 mg/L,含铝0.20 mg/L).其余各组均食用以病区玉米为主加工而成的饲料(含氟110.00 mg/kg,含铝19.70mg/L),饮用自来水配制的高铝水(含氟0.70 mg/L,含铝90.00 mg/L).高氟铝加大豆组在实验开始即添加大豆(大豆占饲料的30%),高氟铝加硒组和高氟铝加螺旋藻组在动物出现氟斑牙后饲料中分别添加硒(3.00mg/kg)、螺旋藻(1000.00 mg/kg),实验期为22周.大鼠处死前收集24 h尿液,用于尿氟、铝的测定;大鼠处死后取四肢骨用于骨氟、铝测定;电镜下观察大鼠股骨松质骨的超微结构变化.结果 ①骨氟:高氟铝组的骨氟[(204.07±63.78)mg/kg]高于对照组、高氟铝加大豆组、高氟铝加硒组和高氟铝加螺旋藻组[(30.06±6.11)、(54.12±14.56)、(30.44±5.02)、(105.08±21.07)mg/kg,t=0.62、0.53、0.62、0.35,P均<0.01];高氟销加硒组骨氟低于高氟钒加螺旋藻组(t=0.27,P<0.01).②尿氟:高氟铝组尿氟[(4.52±3.09)mg/L]高于对照组[(0.89±0.37)mg/L,t=0.23,P<0.01],低于高氟铝加硒组[(10.38±1.58)mg/L,t=0.34,P<0.01];高氟铝加硒组尿氟高于高氟铝加大豆组、高氟铝加螺旋藻组[(5.56±1.69)、(4.38±3.36)mg/L,t=0.28、0.35,P均<0.01].③骨铝:对照组骨铝[(3.32±3.02)mg/kg]明显低于高氟铝组、高氟铝加大豆组、高氟铝加硒组和高氟铝加螺旋藻组[(374.21±56.11)、(118.20±23.59)、(114.01±22.84)、(67.11±11.53)mg/kg,t=1.42、0.44、0.42、0.24,P均<0.05];高氟销组骨铝也明显高于高氟铝加大豆组、高氟铝加硒组、高氟铝加螺旋藻组(t=0.56、0.57、0.68,P均<0.01);高氟铝加螺旋藻组骨铝低于高氟铝加大豆组、高氟铝加硒组(t=0.11、0.10,P均<0.05).④尿铝:高氟铝组尿铝[(1.14±0.32)mg/L]高于对照组、高氟铝加大豆组[(0.73±0.11)、(0.66±0.10)mg/L,t=1.92、2.24,P均<0.05].高氟铝加大豆组尿铝低于高氟铝加硒组、高氟铝加螺旋藻组[(1.03±0.22)、(1.10±0.28)mg/L,t=1.73、2.06,P均<0.05].⑤扫描电镜下高氟铝组骨胶原纤维排列紊乱,骨小梁发生融合成片,小梁吸收孔大多消失,其损害最为严重.在干预组其骨胶原纤维走向大致可见,小梁融合现象较高氟铝组为轻,其中以高氟铝加硒组改善为显著,高氟铝加螺旋藻组次之,而高氟铝加大豆组的作用稍弱.结论 饲料中加大豆、硒粉、螺旋藻对高摄铝状态下氟中毒大鼠的骨损伤具有缓解作用,其中以硒粉的作用最为显著.螺旋藻次之,而大豆的作用稍弱.     

骨软化性氟骨症发生条件与影响因素的实验研究

给大白鼠以玉米为主的偏食饲料,同时经饮水投予氟化钠200ppm,为期两个月,造成骨软化性氟骨症的动物模型。饲料中添加钼,可明显加重骨骼病变;投予蛇纹石,则使病变显著减轻。给饲料补充足量的钙,可防止骨软化性病变的发生。食饵中含钙不足是骨软化性氟骨症发生发展的重要条件。除了减少氟的摄入之外,补充足量的钙和改善胶原代谢,是提高机体抗氟能力,预防骨软化性氟骨症的两条有效途径。     

实验性铝氟联合中毒大鼠骨胳形态计量学研究

用病区高岭土拌煤烘烤玉米饲养大鼠后发现：实验中期高、低铝氟剂量组大鼠出现骨皮质平均厚度、骨小梁平均厚度、骨小梁平均宽度、骨细胞密度等形态计量学指标均减少，实验末期低铝氟剂量组骨骼变化有所改善，结果与阳性对照（铝氟中毒）组病变类似。并对氟与铝对骨骼系统的损伤机理进行了讨论。     

曲美他嗪与厄贝沙坦联用治疗高血压病伴阵发性房颤

目的探讨曲美他嗪联合厄贝沙坦治疗高血压病伴降发性房颤的疗效及对左房内径、C反应蛋白（CRP）的影响。方法入选高血压病伴阵发性房颤患者160例,随机分为单用胺碘酮组（Ⅰ组）、胺碘酮加厄贝沙坦组（Ⅱ组）、胺碘酮加曲美他嗪组（Ⅲ组）、胺碘酮加厄贝沙坦加曲美他嗪组（Ⅳ组）,每组40例,均服药1年。观察4组治疗前后疗效及左房内径、C反应蛋白的变化。结果4组治疗后．有效率Ⅰ组为46．1％,Ⅱ组为65.0％,Ⅲ组为56．4%．Ⅳ组为74．3％,Ⅱ组、Ⅲ组、Ⅳ组与Ⅰ组比较,差异有统计学意义（P〈0．05或P〈0.01）;Ⅱ组与Ⅲ组比较、Ⅳ组与Ⅱ组、Ⅲ组比较．差异均有统计学意义（P〈0．01）。4组治疗前后比较,Ⅱ组、Ⅳ组左房内径减小,Ⅰ组、Ⅲ组左房内径增大,治疗后Ⅱ组、Ⅲ组、Ⅳ组与Ⅰ组比较,差异有统计学意义（P〈0．01）,Ⅱ组、Ⅳ组与Ⅲ组比较、Ⅳ组与Ⅱ组比较,差异均有统计学意义（P〈0.05或P〈0.01）;治疗岳4组血CRP浓度均比治疗前减低。结论曲羡他嗪联合厄贝沙坦能通过抗炎、抑制左房重构作用预防阵发性房颤复发。     

Aging and dietary modulation of rat skeleton and parathyroid hormone

Studies were carried out on SPF F344 male rats to evaluate the effects of aging and life-prolonging food restriction, without malnutrition, on rat skeleton and circulating PTH. Six-week-old F344 rats were divided into five groups. Group 1 rats were fed ad libitum a diet that contained 21% protein. Group 2 rats were fed 60% of the mean food intake of group 1 rats from 6 weeks of age for the rest of their lives. Group 3 rats were fed 60% of the ad libitum food intake until 6 months of age and then switched to ad libitum feeding. Group 4 rats were fed ad libitum until 6 months of age, and then switched to 60% of the ad libitum food intake. Group 5 rats were fed ad libitum a diet that contained only 12.6% protein so that these animals ingested the same amount of protein per day as the group 2 rats. In group 1 animals, bone length, weight, density, and calcium content increased rapidly with age and plateaued at about 12 months of age. There was no evidence of bone loss in these animals until about 24 months of age, but by 27 months, the animals had lost appreciable amounts of bone. The circulating immunoreactive PTH levels of the animals increased with advancing age, with a marked rise at 27 months. The age-related changes in bone and serum PTH levels of rats in groups 3 and 5 were similar to those of group 1 animals, except that a terminal increase in serum PTH did not occur in group 5 rats. In the groups 2 and 4 animals which were food restricted for the longest period, bone growth and maturation were slowed down, but the animals did not experience senile bone loss or marked terminal increase in circulating PTH. The salutary effects of food restriction were, therefore, not due specifically to the restriction of protein intake or to restricting food intake only during the period of rapid growth.     

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。     

氟中毒大鼠听觉脑干诱发反应的特点

目的通过尿、便等指标观察氟中毒大鼠听觉脑干诱发反应(ABR)变化情况,从而进一步探讨氟中毒对听力影响的作用机制。方法选择生后30 d(体重60~100 g)的Wistar大鼠,雌雄不分。实验组3O只,其中实验1组(F组)l5只,喂饮含氟50 mg/L的自来水;实验2组(f组)15只,喂饮含氟100 mg/L的自来水。喂养6个月,制成慢性氟中毒模型。对照组15只。6个月后观察尿、便氟含量等各项指标。在2%戊巴比妥钠轻麻下,首先测定3组鼠的听觉脑干电位,而后取其牙齿观察氟中毒情况。结果实验1组和实验2组有典型的氟斑牙出现,尿、便氟含量差异显著。实验1组和实验2组与对照组相比听觉脑干电位I、Ⅲ、和V波等各波潜伏期时间差异显著(P<0.05),而实验1组与实验2组无差异。结论慢性氟中毒对听力有明显影响,这种听力损失是高频听力损失,慢性氟中毒致听力损失的机制可能是氟致听神经的直接毒作用。     

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.     

慢性氟中毒对大鼠大脑皮质神经细胞活性氧水平和线粒体融合的影响

目的 观察慢性氟中毒对大鼠大脑皮质神经细胞活性氧(ROS)水平和线粒体融合的影响,并分析二者间的关系.方法 选择SD大鼠120只,按性别和体质量随机分为3组:对照组、低氟组、高氟组,每组40只.对照组大鼠自由饮用自来水(含氟量<0.5 mg/L);低、高氟组分别饮用氟化钠(NaF)配制的含氟量为10.0、50.0 mg/L的自来水.分别于3、6个月时处死大鼠,采集大脑组织制作冰冻切片,采用荧光测定法检测皮质神经细胞ROS水平和线粒体形态变化.结果 3、6个月时各组大鼠大脑皮质神经细胞ROS荧光计数和Ⅱ型线粒体计数水平比较,差异有统计学意义(F值分别为3.07、3.06,3.05、3.07,P均<0.05).3个月时,与对照组(10.43±5.98、4.12±3.86)比较,高氟组大鼠大脑皮质神经细胞ROS荧光计数(25.48±6.09)和Ⅱ型线粒体计数(20.47±6.09)明显升高(P均<0.05),而低氟组(11.67±3.49、6.68±3.48)未见明显改变(P均>0.05);6个月时,与对照组(25.26±6.41、20.26±6.41)比较,低、高氟组大鼠大脑皮质神经细胞ROS荧光计数和Ⅱ型线粒体计数(63.02±8.15、65.60±7.40,49.33±8.61、53.10±6.95)均明显增高(P均<0.05).ROS荧光计数与Ⅱ型线粒体计数间呈明显正相关(r值分别为0.93、0.81,P均<0.05).结论 摄入过量的氟导致大鼠大脑皮质神经细胞氧化应激水平升高,线粒体融合功能障碍,这些改变与染氟时间和剂量密切相关.线粒体异常改变的机制可能与慢性氟中毒引起的氧化应激水平升高有关.

Abstract：

Objective To investigate the changes of reactive oxygen species(ROS) level and mitochondria fission-fusion-balance in cortical neurons of rats with chronic fluorosis and reveal the correlation between these two factors. Methods One hundred and twenty rats were randomly divided into 3 groups(control group, low-dose fluorosis group, high-dose fluorosis group) and 40 rats were in each group according to body weight and the experiments were carried out for 3 months or 6 months. 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 group were fed with water containing NaF 10.0,50.0 mg/L, respectively. The level of ROS and the morphology in mitochondria fission-fusion balance in neurons of the cortex of rat brains prepared with cortical frozen sections were detected with ROS fluorescent probe and MitoTracker RED probe, respectively. Results Significant differences of the level of ROS and the numbers of abnormal mitochondria in morphology in the cortical neurons were found between 3 groups at the experiment period of 3 month and 6 month(F= 3.07,3.06,3.05,3.07, all P < 0.05). As compared with control group(10.43 ± 5.98,4.12 ± 3.86) at the experiment period of 3 month, the level of ROS and the numbers of abnormal mitochondria in morphology in the cortical neurons were obviously increased in high-dose fluorosis group(25.48 ± 6.09,20.47 ± 6.09, all P < 0.05), whereas no significant changes were found in low-dose fluorosis group(11.67 ± 3.49,6.68 ± 3.48, all P> 0.05). Furthermore, the increases in both ROS level and abnormal numbers of mitochondria were significant observed in the cortical neurons of low-dose fluorosis group (63.02 ± 8.15, 49.33 ± 8.61) and high-dose fluorosis group(65.60 ± 7.40,53.10 ± 6.95) as compared with the control group (25.26 ± 6.41,20.26 ± 6.41) at the experimental period of 6 month (all P < 0.05). The abnormal numbers of mitochondria correlated with ROS level(r = 0.93,0.81, all P < 0.05). Conclusions Taking excessive amount of fluoride results in high level of oxidative stress and impaired the balance of mitochondrial fission-fusion,which is dependent on the feeding times and doses of fluoride. The mechanism of the mitochondrial abnormalities might be associated with the high level of oxidative stress induced by chronic fluorosis.     

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     

Modulation of age-related hyperparathyroidism and senile bone loss in Fischer rats by soy protein and food restriction

Studies were carried out to explore the influence of soy protein and food restriction on age-related changes in serum PTH and bone. Three groups of male Fischer 344 rats were studied from 6 weeks of age. Group A rats were fed ad libitum diet A, which has casein as the protein source. Group B rats were fed diet B (with casein as protein source) at 60% of the mean ad libitum food intake. Group C rats were fed ad libitum diet C, which has soy protein as the protein source. The animals were killed at periodic intervals beginning at 6 months of age after an overnight fast. Serum PTH, measured with an intact N-terminal-specific RIA, and immunoreactive calcitonin increased progressively with aging. The increase was markedly suppressed by food restriction, and in the case of PTH by the soy protein diet as well. Serum creatinine started to increase after 18 months of age, and both dietary regimens of groups 2 and 3 retarded the increase. Aging was associated with a fall in serum 25-hydroxyvitamin D, and loss of bone occurred during the terminal part of life in the ad libitum-fed animals. These were prevented by food restriction, while the soy protein diet delayed the onset of bone loss. We conclude from these findings and other data from this study that in the male F344 rats 1) an age-related increase in serum PTH precedes an age-related increase in serum creatinine concentration; 2) an age-related decline in renal function probably contributes to age-related hyperparathyroidism, which, in turn, contributes to senile bone loss; 3) food restriction inhibits age-related hyperparathyroidism and senile bone loss; 4) on the basis of the data from rats fed a soy protein-containing diet, a decline in renal function and progressive hyperparathyroidism are not inevitable consequences of aging in the ad libitum fed rats.     

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     

过量氟对大鼠部分组织中钙、镁、磷水平的影响

目的：研究慢性氟中毒大鼠在不同染氟剂量及时间内，体内不同组织中钙（Ca)、镁（Mg)、磷（P）水平的变化，探讨过量氟对不同组织中各元素水平的影响。方法：SD大鼠70只分为对照组和低，中，高剂量染氟组，观察实验后3个月（42只）和5个月（28只）的变化。低钙喂养，3个月及5个月后，取氟中毒大鼠心、肝、肾、脾、肌肉、四肢骨及血清，分析，分析F,Ca,P,Mg含量，结果：大鼠氟后各组织氟含量均有不同程度升高，随时间不同，组织中的氟含量呈现动态过程，经多元逐回归分析，大鼠染氟3个月后肌肉中F与Ca,P，肝脏中F与Mg，四肢骨中F与Mg，心脏中F与Ca呈显著性相关（P＜0．05），染氟5个月后肝脏中F与Ca，四肢骨中F与Mg，心脏中F与Ca，肾脏中F与P，Mg呈显著性相关（P＜0．05）。结论：氟中毒大鼠不同组织中相关元素含量随染氟剂量，时间不同而不同。     

Lifelong dietary modulation of calcitonin levels in rats

Studies were carried out on specific pathogen-free rats to evaluate the effects of aging and dietary manipulation on serum and thyroid calcitonin (CT) levels. Male Fischer 344 rats were randomized at 6 weeks of age to six dietary groups and subsequently maintained on the following dietary regimens. Group 1 rats were fed ad libitum throughout life; group 2 rats were fed 60% of the ad libitum food uptake, but received the same amounts of calcium, phosphorus, and vitamin D; group 3 rats were fed as the group 2 animals until 6 months of age and from then on were fed ad libitum; group 4 rats were fed ad libitum until 6 months of age and then switched to 60% food restriction; group 5 rats were fed ad libitum on food isocaloric with that of group 1 rats, but containing only 60% of the protein. Group 6 rats were killed at 6 weeks of age to serve as baseline controls. Ten rats were killed in each of the remaining five groups 15 h postprandial at 6-month intervals. The following observations were made. Serum CT increased with age similarly in the ad libitum fed group 1 and 5 rats. Food restriction markedly inhibited the increase in serum CT, and the effect was more profound in animals whose food intake was restricted after 6 months of age (group 4) than in animals on lifelong food restriction (group 2). In rats switched from food restriction to ad libitum feeding (group 3) at 6 months of age, serum CT increased with age to levels identical with those of lifelong ad libitum fed group 1 animals. Thyroid CT showed a similar pattern of age-dependent and dietary modulated changes. In contrast, aging and dietary modulation had no appreciable effect on serum calcium levels, except at 27 months of age when the serum calcium level of group 1 animals increased dramatically from the level for 24-month-old animals. There was a weak positive correlation between serum calcium and serum CT (r = 0.627; P = 0.02) and a highly significant positive correlation between serum CT and thyroid CT (r = 0.917; P = 0.001). These findings indicate that elective and therapeutic restriction of food intake might also attenulate CT levels in humans, with potentially adverse implications for skeletal homeostasis.