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猪氟诱导肝损伤过程中半胱天冬酶依赖性细胞凋亡的评估。

Evaluation of caspase-dependent apoptosis during fluoride-induced liver lesion in pigs.

作者信息

Zhan Xiu An, Wang Min, Xu Zi Rong, Li Wei Fen, Li Jian Xin

机构信息

Feed Science Institute, College of Animal Science, Zhejiang University, No. 268, Kaixuan Road, HangZhou, 310029, People's Republic of China.

出版信息

Arch Toxicol. 2006 Feb;80(2):74-80. doi: 10.1007/s00204-005-0019-3. Epub 2005 Sep 1.

DOI:10.1007/s00204-005-0019-3
PMID:16136339
Abstract

Sixteen barrows (Duroc x Landrace x Yorkshire) were randomly divided into two groups, each consisting eight pigs. The groups received the same basal diet supplemented with 0 and 400 mg/kg fluoride, respectively. Histological examinations, including in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), Haematoxylin and Eosin staining (HE) and transmission electron microscopy observation, found apoptotic hepatocytes 50 days after additional 400 mg/kg fluoride treatment. The obvious DNA ladder and the significantly increased both hepatic caspase-9 and caspase-3 activity indicated that fluoride induced caspase-dependent apoptosis in vivo. In addition, serum glutamate pyruvate transaminase (GPT) activity and hepatic lipid peroxides (LPO) concentration was significantly increased. The activity of serum glutamate oxaloacetate transaminase (GOT) showed an increased trend. The results suggest that fluoride induces apoptosis by elevating the oxidative stress-induced lipid peroxidation, causing mitochondrial dysfunction and further activating caspase-9 and caspase-3.

摘要

16头杜洛克×长白×大白杂交仔猪被随机分为两组,每组8头猪。两组分别饲喂添加0和400mg/kg氟的相同基础日粮。组织学检查,包括原位末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法(TUNEL)、苏木精-伊红染色(HE)和透射电镜观察,发现在额外添加400mg/kg氟处理50天后出现凋亡的肝细胞。明显的DNA梯带以及肝脏中半胱天冬酶-9和半胱天冬酶-3活性显著增加,表明氟在体内诱导了半胱天冬酶依赖性凋亡。此外,血清谷丙转氨酶(GPT)活性和肝脏脂质过氧化物(LPO)浓度显著升高。血清谷草转氨酶(GOT)活性呈上升趋势。结果表明,氟通过升高氧化应激诱导的脂质过氧化,导致线粒体功能障碍,进而激活半胱天冬酶-9和半胱天冬酶-3来诱导细胞凋亡。

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