氟中毒大鼠骨、肝、肾及脑组织的病理学变化
|
摘要
目的研究氟化钠对大鼠骨、脑、肝及肾组织病理学的影响。方法选择健康断乳SD大鼠20只,雌雄各半,随机分为对照组和氟中毒组。氟中毒组大鼠自由饮用含氟化钠的自来水(氟离子浓度为100 mg/L),定期称重,测量身长、尾长,并观察氟斑牙及中毒症状。饲养12周后,检测各组大鼠股骨、肝脏、肾脏及脑组织氟含量,测定血清、肝脏、肾脏及脑组织丙二醛(MDA)含量,光镜和电镜下观察各组织的病理学结构变化。结果氟中毒组大鼠摄食量、摄水量、体重、身长及尾长均略低于对照组,但差异无统计学意义;对照组大鼠无氟斑牙发生,氟中毒组大鼠氟斑牙发病率为100%;与对照组相比,氟中毒组大鼠股骨、肝脏、肾脏及脑组织氟含量均显著升高(P<0. 01);氟中毒组大鼠血清及肝脏、肾脏及脑组织MDA含量均高于对照组(P<0. 01或P<0. 05)。光镜结果显示,氟中毒组大鼠骨小梁粗细不均、间距增大;肝细胞部分水肿明显,肝细胞索排列紊乱;肾皮质近曲小管上皮细胞肿胀,管腔增大;海马区神经细胞肿胀和空泡化。电镜下,氟中毒组大鼠成骨细胞、肝细胞、肾脏近曲小管上皮细胞及脑神经元的超微结构均呈现细胞凋亡的典型特征,表现为细胞核固缩,染色质浓聚边集,线粒体肿胀、空泡化。结论氟化钠可引起实验性大鼠骨、肝、肾及脑组织病理性损伤,导致细胞凋亡。
Objective To study the effect of sodium fluoride on the pathological and morphological changes in femur,liver,kidney,and brain tissues of rats with fluorosis. Methods Ten healthy male and ten healthy female weaned Sprague-Dawley rats were randomly divided into a control group and fluorosis group. Rats in the fluorosis group were fed with tap water containing a fluorine ion concentration of 100 mg/L for 12 weeks. Contents of fluoride ion in the femur,liver,kidney,and brain tissues of rats in each group were determined,as well the content of malondialdehyde( MDA) in serum,liver,kidney,and brain. Pathological and morphological changes in the femur,liver,kidney,and brain of rats with fluorosis were observed using light microscopy and transmission electron microscopy( TEM). Results Body weight,body length,and tail length of rats in the fluorosis group were slightly lower than those in the control group,but the incidence of dental fluorosis in rats treated with fluoride was 100%. Fluoride levels in the femur,liver,kidney,and brain tissues of fluorosis group rats were significantly increased compared with the control group( P < 0. 01),and MDA content in serum,liver,kidney,and brain of rats with fluorosis was higher than that of the control group( P < 0. 01 or P < 0. 05).The results of pathological examination in rats with fluorosis revealed: 1) shortened bone trabecula,2) wider trabecular spacing in bone tissue,3) hepatocyte degeneration and vacuolization in liver tissue,4) vacuolar degeneration of epithelial cells in the kidney proximal tubule,as well as mildly congestive and expanded interstitial tubules,and 5) sparsely distributed hippocampal cells exhibiting swelling and vacuolation. Under TEM,all the osteoblasts,hepatocytes,epithelial cells of the kidney proximal tubules, and neurons in rats treated with fluoride all exhibited shrinkage, chromatin margination,and mitochondrial swelling. Conclusions Sodium fluoride can cause pathological damage in the femur,liver,kidney,and brain tissues in rats,and can induce cell apoptosis.
Objective To study the effect of sodium fluoride on the pathological and morphological changes in femur,liver,kidney,and brain tissues of rats with fluorosis. Methods Ten healthy male and ten healthy female weaned Sprague-Dawley rats were randomly divided into a control group and fluorosis group. Rats in the fluorosis group were fed with tap water containing a fluorine ion concentration of 100 mg/L for 12 weeks. Contents of fluoride ion in the femur,liver,kidney,and brain tissues of rats in each group were determined,as well the content of malondialdehyde( MDA) in serum,liver,kidney,and brain. Pathological and morphological changes in the femur,liver,kidney,and brain of rats with fluorosis were observed using light microscopy and transmission electron microscopy( TEM). Results Body weight,body length,and tail length of rats in the fluorosis group were slightly lower than those in the control group,but the incidence of dental fluorosis in rats treated with fluoride was 100%. Fluoride levels in the femur,liver,kidney,and brain tissues of fluorosis group rats were significantly increased compared with the control group( P < 0. 01),and MDA content in serum,liver,kidney,and brain of rats with fluorosis was higher than that of the control group( P < 0. 01 or P < 0. 05).The results of pathological examination in rats with fluorosis revealed: 1) shortened bone trabecula,2) wider trabecular spacing in bone tissue,3) hepatocyte degeneration and vacuolization in liver tissue,4) vacuolar degeneration of epithelial cells in the kidney proximal tubule,as well as mildly congestive and expanded interstitial tubules,and 5) sparsely distributed hippocampal cells exhibiting swelling and vacuolation. Under TEM,all the osteoblasts,hepatocytes,epithelial cells of the kidney proximal tubules, and neurons in rats treated with fluoride all exhibited shrinkage, chromatin margination,and mitochondrial swelling. Conclusions Sodium fluoride can cause pathological damage in the femur,liver,kidney,and brain tissues in rats,and can induce cell apoptosis.
引文
[1] Zhang Z,Zhou B,Wang XH,et al. Maize purple plant pigment protects against sodium fluoride-induced oxidative damage of liver and kidney in rats[J]. Int J Environ Res Public Health,2014,11(1):1020-1033.
[2]王飞清,夏曙华,邹文兵,等.营养元素和蛋白联合干预氟中毒对雌鼠卵巢功能作用[J].中国比较医学杂志,2018,28(7):52-57.
[3]刘洋,韩伦英,何川,等.不同性别氟中毒大鼠模型的比较研究[J].中国比较医学杂志,2018,28(1):33-37.
[4] Varol E,Icli A,Aksoy F,et al. Evaluation of total oxidative status and total antioxidant capacity in patients with endemic fluorosis[J]. Toxicol Ind Health,2013,29(2):175-180.
[5] Jothiramajayam M,Sinha S,Ghosh M,et al. Sodium fluoride promotes apoptosis by generation of reactive oxygen species in human lymphocytes[J]. J Toxicol Environ Health A,2014,77(21):1269-1280.
[6]王连方.氟斑牙的几种“Dean氏分类法”浅析[J].地方病通报,2007,22(1):71-73.
[7]张志瑜,翟城,钱聪,等.高温燃烧水解氟电极法测定骨氟化物水平实验条件的研究[J].中国地方病学杂志,2006,25(4):450-452.
[8]张志瑜,韩冰,钱聪.痕量氟化物快速测定方法建立[J].中国公共卫生,2011,27(2):255-256.
[9] Perumal E,Paul V,Govindarajan V,et al. A brief review on experimental fluorosis[J]. Toxicol Lett,2013,223(2):236-251.
[10] Zuo H,Chen L,Kong M,et al. Toxic effects of fluoride on organisms[J]. Life Sci,2018,198:18-24.
[11] Buzalaf MA,Whitford GM. Fluoride metabolism[J]. Monogr Oral Sci,2011,22:20-36.
[12] Dec K,Lukomska A,Maciejewska D,et al. The influence of fluorine on the disturbances of homeostasis in the central nervous system[J]. Biol Trace Elem Res,2017,177(2):224-234.
[13] Khandare AL,Gourineni SR,Validandi V. Dental fluorosis,nutritional status,kidney damage,and thyroid function along with bone metabolic indicators in school-going children living in fluoride-affected hilly areas of Doda district, Jammu and Kashmir, India[J]. Environ Monit Assess, 2017, 189(11):579.
[14] Qin SL,Deng J,Lou DD,et al. The decreased expression of mitofusin-1 and increased fission-1 together with alterations in mitochondrial morphology in the kidney of rats with chronic fluorosis may involve elevated oxidative stress[J]. J Trace Elem Med Biol,2015,29:263-268.
[15]李惠兰,于燕妮,陈扬,等.燃煤污染型氟中毒大鼠Mn-超氧化物歧化酶mRNA和蛋白水平的改变[J].中华病理学杂志,2012,41(09):627-630.
[16] Nabavi SF,Habtemariam S,Jafari M,et al. Protective role of gallic acid on sodium fluoride induced oxidative stress in rat brain[J]. Bull Environ Contam Toxicol,2012,89(1):73-77.
[17]陈荣,于燕妮,徐淋,等. m TOR自噬通路在染氟大鼠软骨关节损伤中的作用[J].中国地方病防治志,2017,32(1):18-19.
[18] Liu L,Zhang Y,Gu H,et al. Fluorosis induces endoplasmic reticulum stress and apoptosis in osteoblasts in vivo[J]. Biol Trace Elem Res,2015,164(1):64-71.
[19]郑冬冬,周涛,段小红.活体小动物显微CT对氟中毒小鼠骨质特征的分析[J].实用口腔医学杂志,2013,29(2):181-184.
[20] Liu F, Ma J, Zhang H, et al. Fluoride exposure during development affects both cognition and emotion in mice[J].Physiol Behav,2014,124:1-7.
[21] Rashid K,Sinha K,Sil PC. An update on oxidative stressmediated organ pathophysiology[J]. Food Chem Toxicol,2013,62:584-600.
[22] Zuo H,Chen L,Kong M,et al. Toxic effects of fluoride on organisms[J]. Life Sci,2018,198:18-24.
[23] Tsikas D. Assessment of lipid peroxidation by measuring malondialdehyde(MDA)and relatives in biological samples:analytical and biological challenges[J]. Anal Biochem,2017,524:13-30.
[24] Barbier O, Arreola-Mendoza L, Del Razo LM. Molecular mechanisms of fluoride toxicity[J]. Chem Biol Interact,2010,188(2):319-333.
[25] Chlubek D. Fluoride and oxidative stress[J]. Fluoride,2003,36(4):217-228.
[26]官志忠,刘家骥.氟的细胞毒作用[J].贵阳医学院学报,1985,10(4):287-290.
[2]王飞清,夏曙华,邹文兵,等.营养元素和蛋白联合干预氟中毒对雌鼠卵巢功能作用[J].中国比较医学杂志,2018,28(7):52-57.
[3]刘洋,韩伦英,何川,等.不同性别氟中毒大鼠模型的比较研究[J].中国比较医学杂志,2018,28(1):33-37.
[4] Varol E,Icli A,Aksoy F,et al. Evaluation of total oxidative status and total antioxidant capacity in patients with endemic fluorosis[J]. Toxicol Ind Health,2013,29(2):175-180.
[5] Jothiramajayam M,Sinha S,Ghosh M,et al. Sodium fluoride promotes apoptosis by generation of reactive oxygen species in human lymphocytes[J]. J Toxicol Environ Health A,2014,77(21):1269-1280.
[6]王连方.氟斑牙的几种“Dean氏分类法”浅析[J].地方病通报,2007,22(1):71-73.
[7]张志瑜,翟城,钱聪,等.高温燃烧水解氟电极法测定骨氟化物水平实验条件的研究[J].中国地方病学杂志,2006,25(4):450-452.
[8]张志瑜,韩冰,钱聪.痕量氟化物快速测定方法建立[J].中国公共卫生,2011,27(2):255-256.
[9] Perumal E,Paul V,Govindarajan V,et al. A brief review on experimental fluorosis[J]. Toxicol Lett,2013,223(2):236-251.
[10] Zuo H,Chen L,Kong M,et al. Toxic effects of fluoride on organisms[J]. Life Sci,2018,198:18-24.
[11] Buzalaf MA,Whitford GM. Fluoride metabolism[J]. Monogr Oral Sci,2011,22:20-36.
[12] Dec K,Lukomska A,Maciejewska D,et al. The influence of fluorine on the disturbances of homeostasis in the central nervous system[J]. Biol Trace Elem Res,2017,177(2):224-234.
[13] Khandare AL,Gourineni SR,Validandi V. Dental fluorosis,nutritional status,kidney damage,and thyroid function along with bone metabolic indicators in school-going children living in fluoride-affected hilly areas of Doda district, Jammu and Kashmir, India[J]. Environ Monit Assess, 2017, 189(11):579.
[14] Qin SL,Deng J,Lou DD,et al. The decreased expression of mitofusin-1 and increased fission-1 together with alterations in mitochondrial morphology in the kidney of rats with chronic fluorosis may involve elevated oxidative stress[J]. J Trace Elem Med Biol,2015,29:263-268.
[15]李惠兰,于燕妮,陈扬,等.燃煤污染型氟中毒大鼠Mn-超氧化物歧化酶mRNA和蛋白水平的改变[J].中华病理学杂志,2012,41(09):627-630.
[16] Nabavi SF,Habtemariam S,Jafari M,et al. Protective role of gallic acid on sodium fluoride induced oxidative stress in rat brain[J]. Bull Environ Contam Toxicol,2012,89(1):73-77.
[17]陈荣,于燕妮,徐淋,等. m TOR自噬通路在染氟大鼠软骨关节损伤中的作用[J].中国地方病防治志,2017,32(1):18-19.
[18] Liu L,Zhang Y,Gu H,et al. Fluorosis induces endoplasmic reticulum stress and apoptosis in osteoblasts in vivo[J]. Biol Trace Elem Res,2015,164(1):64-71.
[19]郑冬冬,周涛,段小红.活体小动物显微CT对氟中毒小鼠骨质特征的分析[J].实用口腔医学杂志,2013,29(2):181-184.
[20] Liu F, Ma J, Zhang H, et al. Fluoride exposure during development affects both cognition and emotion in mice[J].Physiol Behav,2014,124:1-7.
[21] Rashid K,Sinha K,Sil PC. An update on oxidative stressmediated organ pathophysiology[J]. Food Chem Toxicol,2013,62:584-600.
[22] Zuo H,Chen L,Kong M,et al. Toxic effects of fluoride on organisms[J]. Life Sci,2018,198:18-24.
[23] Tsikas D. Assessment of lipid peroxidation by measuring malondialdehyde(MDA)and relatives in biological samples:analytical and biological challenges[J]. Anal Biochem,2017,524:13-30.
[24] Barbier O, Arreola-Mendoza L, Del Razo LM. Molecular mechanisms of fluoride toxicity[J]. Chem Biol Interact,2010,188(2):319-333.
[25] Chlubek D. Fluoride and oxidative stress[J]. Fluoride,2003,36(4):217-228.
[26]官志忠,刘家骥.氟的细胞毒作用[J].贵阳医学院学报,1985,10(4):287-290.