摘要
畜禽水和食物中广泛存在的氟严重威胁着畜禽的肝健康和动物性食品的安全。为阐明氟致肝损伤的内在机制,明确IL-17A在氟诱导肝炎症反应和肝细胞凋亡中的调节作用,本研究将24只野生型C57小鼠和12只IL-17A基因敲除小鼠随机分为对照组、NaF组、KO+NaF组。同时,运用HE染色观察肝的组织形态变化,并通过ELISA、流式细胞术、免疫组化检测肝中炎症细胞、炎症因子、凋亡的变化情况。结果显示,氟暴露诱导了肝组织结构损伤,增加了肝中炎症因子(TNF-α、IL-17A、INF-γ、IL-23、TGF-β)、M2型巨噬细胞和树突状细胞的水平,并降低了IL-1β、自然杀伤细胞、γδT细胞、CD4^(+)T细胞水平和CD4^(+)T细胞/CD8^(+)T细胞比值。同时,凋亡检测结果显示,氟暴露增加了肝中凋亡细胞的数量和凋亡关键基因(Cyt-c、Caspase3)的蛋白表达水平。然而,与NaF组相比,KO+NaF组的肝损伤减轻,肝中炎症因子(TNFα、IL-17A、INF-γ、IL-23、TGF-β)和树突状细胞含量显著降低,IL-1β表达水平显著升高,且凋亡细胞数量、Cyt-c和Caspase3的蛋白表达水平显著降低。综上表明,IL-17A基因敲除能够缓解氟诱导的炎症反应和肝细胞凋亡。本研究为氟中毒性肝损伤的研究和科学防治提供理论依据和新思路。
The fluoride widely present in water and food of livestock and poultry seriously threatens the liver health of livestock and poultry and the safety of animal food.To elucidate the internal mechanism of fluoride-induced liver injury,and clarify the regulatory role of IL-17A in fluoride-induced liver inflammation and hepatocyte apoptosis,this study randomly divided 24 wild-type C57 mice and 12 IL-17A knockout mice into control,NaF,and KO+NaF groups.In addition,HE staining,ELISA,flow cytometry,and immunohistochemistry were used to detect the changes of morphology,inflammatory cells,inflammatory factors,and apoptosis in the liver.The results showed that fluoride exposure induced liver morphology damage,increased the content of inflammatory factors(TNF-α,IL-17A,INF-γ,IL-23,TGF-β)and the levels of M2 macrophages and dendritic cells,decreased the levels of IL-1β,natural killer cells,γδT cells,CD4^(+)T cells and the ratio of CD4^(+)T cells/CD8^(+)T cells in the liver.In addition,the results of apoptosis detection showed that fluoride exposure increased the apoptotic cells and the protein expression levels of key apoptosis genes Cyt-c and Caspase3 in the liver.However,compared with the NaF group,the liver injury was alleviated,the contents of inflammatory factors(INF-γ,TNF-α,TGF-β,IL-23,IL-17A)and dendritic cells were significantly reduced,and the number of apoptotic cells and the protein expression levels of Cyt-c and Caspase3 were significantly decreased in the liver of KO+NaF group.In summary,IL-17A knockout alleviated fluoride-induced inflammatory response and hepatocyte apoptosis.This study provides theoretical basis and new ideas for the research and the scientific prevention/treatment of fluorotoxic liver injury.
作者
赵阳飞
于洋欢
王金明
张建海
孙子龙
牛瑞燕
王俊东
ZHAO Yangfei;YU Yanghuan;WANG Jinming;ZHANG Jianhai;SUN Zilong;NIU Ruiyan;WANG Jundong(College of Veterinary Medicine,Shanxi Agricultural University,Taigu 030801,China)
出处
《畜牧兽医学报》
CAS
CSCD
北大核心
2023年第7期3108-3117,共10页
ACTA VETERINARIA ET ZOOTECHNICA SINICA
基金
山西省应用基础研究计划(20210302124063)。
