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阿苯达唑对感染小鼠细胞因子和趋化因子应答谱的影响。

Impact of Albendazole on Cytokine and Chemokine Response Profiles in -Inoculated Mice.

机构信息

State Key Laboratory of Pathogenesis, Prevention, Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi 830054, China.

Department of Liver & Laparoscopic Surgery, Digestive & Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China.

出版信息

Biomed Res Int. 2021 May 7;2021:6628814. doi: 10.1155/2021/6628814. eCollection 2021.

Abstract

OBJECTIVE

Alveolar echinococcosis (AE) is a zoonosis caused by the larval stage of the metacestode with a tumor-like behavior in the targeted organ, especially in the liver. Surgery with albendazole is first-line modality for AE. Drug discontinuation is usually based upon the parasitic viability shown by the positron emission tomography (PET) scan. However, as a demanding and expensive method, it is not widely practiced in majority of the endemic regions. Further understanding on the cytokine and chemokine response profiles in AE patients may provide an interesting insight for potential markers in viability assessment.

METHODS

Mice were inoculated with intrahepatically to develop the hepatic AE murine model. Oral albendazole administration was then applied for three months after the first inoculation, and peripheral and regional immune cells including type 1 T helper cells (Th), Th2, Th17, regulatory T (Treg) cells, related cytokines, and chemokines were examined.

RESULTS

The hepatic AE lesion was confirmed by ultrasound examination resulting in a successful rate of 70%. Among the 17 cytokines and chemokines detected, plasma levels of IL-23 were significantly higher in -infected mice when compared to the control group; furthermore, more obvious increasing levels were found after albendazole treatment ( < 0.05). All chemokine levels other than eotaxin and MCP-3 were slightly higher in -infected mice compared to the control group ( > 0.05). Eotaxin levels were significantly decreased in mice with infection followed by albendazole treatment ( < 0.05). Both IL-17A and IL-23 expressions in hepatic AE lesions were significantly higher and related with disease activity.

CONCLUSION

Albendazole administration influenced the balance of immune response and promotes the secretion of proinflammatory factors which is beneficial to parasite clearance. IL-23 seems to be associated with the successful albendazole treatment in mice with infection; such a change could be translated into clinical application in the near future.

摘要

目的

泡型包虫病(AE)是一种由幼虫期引起的人畜共患病,在靶器官中表现出肿瘤样行为,尤其是在肝脏中。阿苯达唑手术是 AE 的一线治疗方法。药物停药通常基于正电子发射断层扫描(PET)扫描显示的寄生虫活力。然而,作为一种要求高且昂贵的方法,它在大多数流行地区并未广泛应用。进一步了解 AE 患者细胞因子和趋化因子反应谱可能为潜在的生存能力评估标志物提供有趣的见解。

方法

将小鼠肝内接种以建立肝泡型包虫病小鼠模型。首次接种后,给予阿苯达唑口服治疗三个月,检测外周和局部免疫细胞,包括 1 型辅助性 T 细胞(Th)、Th2、Th17、调节性 T(Treg)细胞、相关细胞因子和趋化因子。

结果

超声检查证实肝泡型包虫病病变,成功率为 70%。在检测到的 17 种细胞因子和趋化因子中,与对照组相比,感染小鼠的血浆白细胞介素 23(IL-23)水平显著升高;并且在阿苯达唑治疗后发现更明显的升高水平(<0.05)。与对照组相比,感染小鼠的除嗜酸性粒细胞趋化因子和单核细胞趋化蛋白 3(MCP-3)外的所有趋化因子水平均略高(>0.05)。阿苯达唑治疗后感染小鼠的嗜酸性粒细胞趋化因子水平显著降低(<0.05)。肝泡型包虫病病变中的白细胞介素 17A 和白细胞介素 23 表达均显著升高,与疾病活动度相关。

结论

阿苯达唑给药影响免疫反应平衡并促进促炎因子的分泌,有利于寄生虫清除。IL-23 似乎与感染小鼠中阿苯达唑治疗的成功相关;这种变化在不久的将来可能转化为临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12f1/8121589/3e7e23d946df/BMRI2021-6628814.001.jpg

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