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原儿茶酸在传染性法氏囊病病毒感染早期的促凋亡作用。

Pro-apoptosis effects of protocatechuic acid in the early stage of infectious bursal disease virus infection.

机构信息

Postdoctoral Research Base, Henan Institute of Science and Technology, Xinxiang, 453003, Henan, China; College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, 453003, Henan, China.

College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, 453003, Henan, China.

出版信息

Microb Pathog. 2018 Nov;124:216-222. doi: 10.1016/j.micpath.2018.08.030. Epub 2018 Aug 24.

Abstract

Infectious bursal disease virus (IBDV) is a very important small RNA virus in the family of Birnaviridae, which can cause severe immunosuppressive effects and pathological damages in young chickens. It can replicate in bursal lymphocytes and impede the growth and development of B cells, finally causing bursal lymphocytes apoptosis. Previous results have shown that protocatechuic acid (PCA) as an important phenolic compound could effectively improve the survival rate of chickens infected with IBDV. The current study aimed to explore how PCA influenced the pathogenesis of IBDV, especially lymphocyte apoptosis in the process of IBDV infection. The results showed that PCA could effectively alleviate bursal pathological changes at the early stage of IBDV invasion. Moreover, bursal lymphocyte apoptosis for tissue section samples was largely elevated by PCA by using the terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) method while the bursal lymphocyte apoptosis ratio was also increased by PCA by flow cytometry in the early stage of IBDV infection in vivo. Meanwhile, PCA could promote non-lymphocyte apoptosis in vitro. Further study displayed that the potential mechanisms mainly relied on regulation of the expressions of pro-apoptotic protein Bax and anti-apoptotic Bcl-2, thus speeding up the process of IBDV-infected cell apoptosis and preventing virus infection. Meanwhile, the results displayed that the PI3K/Akt and NF kappa B signal pathways might play an important role in promoting cell apoptosis after IBDV infection. Overall, PCA as a potent antiviral drug precursor is expected to be applied in the poultry industry as a substitute for clinical antiviral application.

摘要

传染性腔上囊炎病毒(IBDV)是双RNA 病毒科的一种非常重要的小 RNA 病毒,可导致雏鸡严重的免疫抑制作用和病理损伤。它可以在腔上囊淋巴细胞中复制,并阻碍 B 细胞的生长和发育,最终导致腔上囊淋巴细胞凋亡。先前的研究结果表明,原儿茶酸(PCA)作为一种重要的酚类化合物,可有效提高感染 IBDV 的鸡的存活率。本研究旨在探讨 PCA 如何影响 IBDV 的发病机制,特别是在 IBDV 感染过程中淋巴细胞凋亡。结果表明,PCA 可有效减轻 IBDV 早期入侵时的腔上囊病理变化。此外,通过 TUNEL 法,PCA 可大大提高组织切片中腔上囊淋巴细胞凋亡,而在体内 IBDV 感染的早期阶段,通过流式细胞术,PCA 也可提高腔上囊淋巴细胞凋亡率。同时,PCA 可促进体外非淋巴细胞凋亡。进一步的研究表明,潜在的机制主要依赖于促凋亡蛋白 Bax 和抗凋亡 Bcl-2 的表达调节,从而加速 IBDV 感染细胞的凋亡过程并防止病毒感染。同时,研究结果表明,PI3K/Akt 和 NF kappa B 信号通路可能在促进 IBDV 感染后细胞凋亡中起重要作用。总之,作为一种潜在的抗病毒药物前体,PCA 有望在禽类养殖业中作为临床抗病毒应用的替代品。

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