The Association Between Thyroid Injury and Apoptosis, and Alterations of Bax, Bcl-2, and Caspase-3 mRNA/Protein Expression Induced by Nickel Sulfate in Wistar Rats

The Association Between Thyroid Injury and Apoptosis, and Alterations of Bax, Bcl-2, and Caspase-3 mRNA/Protein Expression Induced by Nickel Sulfate in Wistar Rats
复制标题

Wistar 大鼠甲状腺损伤与细胞凋亡之间的关系,以及硫酸镍诱导的 Bax、Bcl-2 和 Caspase-3 mRNA/蛋白表达的改变(第 72 卷,第 782 页,2017 年)

DOI:
10.1007/s12011-019-02010-z
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发表时间:
2020-05-01
影响因子:
3.9
通讯作者:
Ren, Xuan
Ren, Xuan
中科院分区:
生物学3区
文献类型:
--
作者:
Liu, Yahong;Chen, Hui;Ren, Xuan

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为研究硫酸镍(NiSO4)对甲状腺组织的毒性作用,探讨细胞凋亡的可能机制,将32只雄性Wistar大鼠随机分为对照组(生理盐水,ip)、低剂量组(NiSO4,2.5 mg/kg,ip)、中剂量组(NiSO4,5 mg/kg,ip)、高剂量组(NiSO4,10 mg/kg,ip)。连续治疗40d后,高剂量组大鼠甲状腺出现明显的病理改变。血清游离T-4和促甲状腺激素水平明显低于对照组(F=4.992,p=0.016;F=4.524,p=0.012)。NiSO4各剂量组Caspase-3mRNA表达均显著升高(F=10.259,p=0.014),Bcl2mRNA表达仅高剂量组显著降低(F=9.225,p=0.018)。对照组和NiSO4处理组Bax基因的mRNA表达均无明显变化。Bcl2/Bax比值随NiSO4暴露剂量的增加而降低(F=13.382,p=0.015)。高剂量组Fas基因表达上调(F=66.632,p<0.001)。免疫组织化学检测Caspase-3、Fas、Bax蛋白表达与mRNA表达一致。实验组Bcl2蛋白表达明显低于对照组(F=3.873,p=0.025)。NiSO4作为一种内分泌干扰物,可能通过细胞凋亡诱导甲状腺损伤,导致甲状腺功能减退。甲状腺组织细胞凋亡与Caspase-3、Bcl2、Fas基因和蛋白表达变化密切相关。
To study the toxicity induced by Nickel sulfate (NiSO4) on thyroid tissue, and investigate the role of apoptosis as the possible mechanism, thirty-two male Wistar rats were randomly divided into control group (normal saline, ip), low dose group (2.5 mg/kg day NiSO4, ip), middle dose group (5 mg/kg day NiSO4, ip), high dose group (10 mg/kg day NiSO4, ip). After 40 consecutive days of treatment, there were obvious pathological changes in the thyroids of high dose group. Free T-4 (FT4) and thyroid-stimulating hormone (TSH) were significantly lower in the NiSO4-treated groups than those in the control group (F = 4.992, p = 0.016; F = 4.524, p = 0.012). The mRNA expression of Caspase-3 was significantly higher (F = 10.259, p = 0.014) in all NiSO4-treated groups, and the mRNA expression of Bcl-2 was significantly lower (F = 9.225, p = 0.018) only in the high dose group. Both control group and the NiSO4-treated groups showed no changes in the mRNA expression of Bax gene. The ratio of Bcl-2/Bax decreased with the increase in exposure dose of NiSO4 (F = 13.382, p = 0.015). The mRNA expression of Fas went up in high dose group (F = 66.632, p < 0.001). The Caspase-3, Fas, and the Bax protein expressions measured by immunohistochemistry were consistent with the mRNA expression. The expression of Bcl-2 protein was significantly lower in the test groups than in the control group (F = 3.873, p = 0.025). NiSO4 as an Endocrine Disrupting Chemical may induce the thyroid injury through apoptosis and lead to hypothyroidism. Also, apoptosis in thyroid tissues was closely related to the alternations of Caspase-3, Bcl-2, and Fas mRNA and protein expression.