Deng Chao-nan, Yu Yan-ni, Xie Ying, Zhao Li-na
Department of Pathology,Guiyang Medcial University,Guiyang 550004, China.
Department of Pathology,Guiyang Medcial University,Guiyang 550004, China. Email:
Zhonghua Yu Fang Yi Xue Za Zhi. 2013 Dec;47(12):1142-7.
To discuss the significance of calcineurin (CaN) and nuclear factor of active T cells 1 (NFATc1) in the damage mechanism of the testis of rats with chronic fluorosis.
Eighteen clear class SD male rats, aging 6 week-old, were randomly divided into 3 groups, 6 rats in each. The rats of control group were fed with tap water (NaF < 1 mg/L) and the experimental rats were exposed to NaF (lower group: 5 mg/L, higher group: 50 mg/L) to established the chronic fluorosis model. After 8 months, we observed the occurrence of dental fluorosis among rats in different groups, and the contents of urine fluoride were detected by fluorine ion selective electrode method. The body of the rats were weighted as well as their testis. The testis tissues were stained with hematoxylin-eosin and observed under light microscope to find the morphological changes. The expression of CaN and NFATc1's protein and mRNA in testis were detected by Immunocytochemistry (IHC) and In-situ hybridization (ISH).
The number of rats which was found dental fluorosis were separately 0, 4 and 5 in control group, low dose group and high dose group (χ(2) = 10.60, P < 0.05). The contents of urine fluoride were gradually increased in control group, low group and high group, which were (1.26 ± 0.17), (2.06 ± 0.64) and (7.69 ± 1.96)mg/L, respectively (F = 36.57, P < 0.05). The body weight were significantly different in all three groups(629.00 ± 16.00), (585.17 ± 17.27), (560.50 ± 16.07)g, F = 26.67, P < 0.05) and the testis weight were without statistical difference ((2.58 ± 0.17), (2.43 ± 0.31), (2.35 ± 0.38)g, F = 0.91, P > 0.05). Compared with the control group, the testicular structures were damaged in the experimental groups and especially significant in high dose group. The expression of CaN (59.10 ± 5.62, 77.93 ± 4.16, 101.69 ± 6.31, F = 74.18, P < 0.05) and NFATc1's (76.11 ± 4.41, 93.42 ± 3.85, 120.42 ± 9.31, F = 92.4, P < 0.05) protein in testis tissues were increased by the fluorine concentration. The mRNA expression of CaN and NFATc1 were separately (CaN: 58.76 ± 7.70, 82.01 ± 6.88, 99.47 ± 8.33, F = 42.65, P < 0.05 and NFATc1: 59.39 ± 4.74, 90.02 ± 5.37, 121.15 ± 7.69, F = 155.47, P < 0.05). There were positive correlation between the expression of CaN and NFATc1's protein and mRNA expression (r = 0.899, r = 0.908).
The changes in the signaling pathway of expression of CaN may be involved in the injury mechanism of testis tissues of rats with chronic fluorosis.
探讨钙调神经磷酸酶（CaN）和活化T细胞核因子1（NFATc1）在慢性氟中毒大鼠睾丸损伤机制中的意义。
将18只6周龄清洁级SD雄性大鼠随机分为3组，每组6只。对照组大鼠饮用自来水（NaF<1mg/L），实验组大鼠分别饮用含NaF 5mg/L（低剂量组）和50mg/L（高剂量组）的水以建立慢性氟中毒模型。8个月后，观察不同组大鼠氟斑牙的发生情况，采用氟离子选择电极法检测尿氟含量。称量大鼠体重及睾丸重量。取睾丸组织进行苏木精-伊红染色，光镜下观察形态学变化。采用免疫细胞化学（IHC）和原位杂交（ISH）检测睾丸组织中CaN和NFATc1蛋白及mRNA的表达。
对照组、低剂量组和高剂量组出现氟斑牙的大鼠数分别为0只、4只和5只（χ(2)=10.60，P<0.05）。对照组、低剂量组和高剂量组尿氟含量逐渐升高，分别为（1.26±0.17）、（2.06±0.64）和（7.69±1.96）mg/L（F=36.57，P<0.05）。三组大鼠体重差异有统计学意义（629.00±16.00）、（585.17±17.27）、（560.50±16.07）g，F=26.67，P<0.05），而睾丸重量差异无统计学意义（（2.58±0.17）、（2.43±0.31）、（2.35±0.38）g，F=0.91，P>0.05）。与对照组相比，实验组睾丸结构受损，高剂量组尤为明显。随着氟浓度升高，睾丸组织中CaN蛋白表达（59.10±5.62、77.93±4.16、101.69±6.31，F=74.18，P<0.05）及NFATc1蛋白表达（76.11±4.41、93.42±3.85、120.42±9.31，F=92.4，P<0.05）均增加。CaN和NFATc1的mRNA表达分别为（CaN：58.76±7.70、82.01±6.88、99.47±8.33，F=42.65，P<0.05；NFATc1：59.39±4.74、90.02±5.37、121.15±7.69，F=155.47，P<0.05）。CaN和NFATc1蛋白表达与mRNA表达呈正相关（r=0.899，r=0.908）。
CaN表达信号通路的改变可能参与慢性氟中毒大鼠睾丸组织的损伤机制。
