白细胞介素- 17a对病毒性心肌炎小鼠抗ant抗体及细胞因子的影响。

IF 2.7 4区 医学 Q3 VIROLOGY
Weiwei Li, Wei Jiao, Fang Li, Jie Hao
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引用次数: 0

摘要

目的:观察白细胞介素- 17a (IL-17A)对病毒性心肌炎(VMC)小鼠血清抗线粒体内体ADP/ATP载体自身抗体(anti-ANT抗体)水平及细胞因子的影响。方法:雄性野生型(WT)和IL-17A敲除型(IL-17A-/-) BALB/c小鼠腹腔注射柯萨奇病毒B3 (CVB3)建立VMC模型(VMC-WT和VMC-IL-17A-/-), WT型BALB/c小鼠腹腔注射PBS建立正常对照组(WT组)。14d后取心肌组织计算心脏质量,制作石蜡切片,HE染色,观察心肌组织病理变化,计算心肌组织病理评分。采用流式细胞术检测外周血CD4+ T淋巴细胞水平,ELISA检测血清中抗ant抗体、IL-17、IL-23水平,Western blotting检测心肌组织中IL-17、IL-23蛋白表达水平。结果:成功构建VMC小鼠。WT组小鼠无异常活动;VMC-WT组小鼠从注射第3天开始逐渐出现蜷缩、耸肩、颤抖等行为,反应较差;VMC-IL-17A-/-组小鼠出现上述症状的程度较轻。VMC-WT组HM、病理评分分别为5.62±0.27 g/kg、3.12±0.45分。VMC-IL-17A-/-组HM和病理评分均低于VMC-WT组。WT小鼠病理检查未见炎症细胞浸润和斑片状坏死。VMC-WT组大鼠显微镜下可见广泛的炎症细胞浸润和心肌细胞大面积坏死。与VMC-WT组比较,CVB3感染14天后,VMC-IL-17A-/-组出现局灶性心肌坏死,炎症细胞浸润明显减少。与此同时,VMC-WT小鼠的CD4+T百分比明显低于WT小鼠。VMC-IL-17A-/-组CD4+T百分比(27.54±3.62)高于VMC-WT组(16.97±2.18)。此外,VMC-IL-17A-/-小鼠血清中抗ant抗体(1.48±0.31 μg/L)、IL-17(33.47±4.26 pg/mL)和IL-23(32.42±4.31 pg/mL)水平显著低于VMC-WT小鼠。在蛋白水平上,IL-17和IL-23的表达结果一致。结论:VMC小鼠血清抗ant抗体、IL-17、IL-23水平显著升高。虽然ELISA结果提示IL-17A参与了VMC小鼠抗ant抗体的产生,但不能完全排除其交叉反应的可能性;因此,研究结果应谨慎解读。IL-17A基因敲低与VMC小鼠心肌炎症抑制、外周血CD4+ T淋巴细胞升高、心肌损伤减轻有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Effect of interleukin-17A on anti-ANT antibodies as well as cytokines in viral myocarditis mice.

Objective: To observe the effect of interleukin-17A (IL-17A) on serum anti-mitochondrial endosomal ADP/ATP carrier autoantibody (anti-ANT antibody) levels and cytokines in viral myocarditis (VMC) mice.

Methods: Male wild-type (WT) and IL-17A knockout (IL-17A-/-) BALB/c mice were intraperitoneally injected with coxsackievirus B3 (CVB3) to establish a VMC model (VMC-WT and VMC-IL-17A-/-), while WT BALB/c mice were injected with PBS intraperitoneally to establish a normal control group (WT group). After 14 days, myocardial tissues were taken to calculate heart mass, and paraffin sections were prepared and stained with HE staining to observe the pathological changes and calculate the pathological score of myocardial tissues. Flow cytometry was used to detect the level of CD4+ T lymphocytes in peripheral blood, ELISA was used to determine the level of anti-ANT antibody, IL-17 and IL-23 in serum, and Western blotting was used to detect the expression level of IL-17 and IL-23 proteins in myocardial tissue.

Results: VMC mice were successfully constructed. Mice in the WT group showed no abnormal activity; Mice in the VMC-WT group gradually showed behaviors such as huddling, shrugging, trembling, and poor response from the third day of injection; Mice in the VMC-IL-17A-/- group showed the above symptoms to a lesser extent. In the VMC-WT group, the HM and pathological score were 5.62 ± 0.27 g/kg and 3.12 ± 0.45 score. The HM and pathologic score in the VMC-IL-17A-/- group were lower than those in the VMC-WT group. The pathological examination of WT mice showed no inflammatory cell infiltration and patchy necrosis. The rats in VMC-WT group showed extensive inflammatory cell infiltration and large sheet necrosis of cardiomyocytes under microscope. Compared with the VMC-WT group, the VMC-IL-17A-/- group showed focal myocardial necrosis and significantly reduced inflammatory cell infiltration 14 days after CVB3 infection. At the same time, the percentage of CD4+T was remarkably lower in the VMC-WT mice compared with the WT mice. The percentage of CD4+T was higher in the VMC-IL-17A-/- group (27.54 ± 3.62) than in the VMC-WT group (16.97 ± 2.18). In addition, anti-ANT antibody (1.48 ± 0.31 μg/L), IL-17 (33.47 ± 4.26 pg/mL) and IL-23 (32.42 ± 4.31 pg/mL) levels were significantly lower in serum of VMC-IL-17A-/- mice than in the VMC-WT mice. At the protein level, the expression of IL-17 and IL-23 showed consistent results.

Conclusion: Serum anti-ANT antibody, IL-17, and IL-23 levels were significantly elevated in VMC mice. Although the ELISA results suggest IL-17A is involved in the production of anti-ANT antibody in VMC mice, the possibility of cross-reactivity cannot be completely ruled out; therefore, the results should be interpreted with caution. The knockdown of IL-17A gene was associated with inhibition of myocardial inflammation, elevation of peripheral blood CD4+ T lymphocytes, and attenuation of myocardial injury in VMC mice.

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来源期刊
Virus research
Virus research 医学-病毒学
CiteScore
9.50
自引率
2.00%
发文量
239
审稿时长
43 days
期刊介绍: Virus Research provides a means of fast publication for original papers on fundamental research in virology. Contributions on new developments concerning virus structure, replication, pathogenesis and evolution are encouraged. These include reports describing virus morphology, the function and antigenic analysis of virus structural components, virus genome structure and expression, analysis on virus replication processes, virus evolution in connection with antiviral interventions, effects of viruses on their host cells, particularly on the immune system, and the pathogenesis of virus infections, including oncogene activation and transduction.
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