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依古珠单抗减少 B 细胞分泌免疫球蛋白,从而在间质性肺病中发挥保护作用。

Iguratimod reduces B-cell secretion of immunoglobulin to play a protective role in interstitial lung disease.

机构信息

Department of Clinical Immunology, PLA Specialized Research Institute of Rheumatology & Immunology, Xijing Hospital, Fourth Military Medical University, No. 127 West Changle Road, Xi'an, Shaanxi Province, China; National Translational Science Center for Molecular Medicine, Xi'an, China.

Department of Clinical Immunology, PLA Specialized Research Institute of Rheumatology & Immunology, Xijing Hospital, Fourth Military Medical University, No. 127 West Changle Road, Xi'an, Shaanxi Province, China; National Translational Science Center for Molecular Medicine, Xi'an, China.

出版信息

Int Immunopharmacol. 2021 Aug;97:107596. doi: 10.1016/j.intimp.2021.107596. Epub 2021 Apr 20.

Abstract

OBJECTIVE

Our study aimed to investigate the effect of Iguratimod (IGU) on bleomycin (BLM)-induced interstitial lung disease (ILD).

METHODS

The pulmonary fibrosis model group mice were developed by intratracheal injection of BLM. Mice were divided into two groups at random: (1) Control group (BLM group) - endotracheal BLM (BLM, 3.5 mg/kg, Kayaku, Japan) plus an intraperitoneal injection of normal saline, and (2) BLM + IGU group - intratracheal BLM (same as the control group) + IGU intraperitoneal injection (50 mg/kg/d). The alveolar lavage fluid, histopathology/immunohistochemistry, imaging, and other tests were performed on days 7, 14, 21, and 28 after injection.

RESULTS

Lung function, including Compliance (Crs),Tissue damping (G), Static compliance (Cst), Inspiratory capacity (IC), Elastance (Ers), Tissue elastance (H) and Respiratory system resistance (Rrs) in mice, was improved by IGU. IGU reduced BLM-induced changes in pulmonary fibrosis and pulmonary inflammation, as shown in histological examination.Collagen production and inflammatory damage in the lungs caused by BLM were also reduced by IGU. IGU reduced the expression of immunoglobulin IgG and type I collagen in BLM-induced pulmonary fibrosis mice by inhibiting the production of B cells and immunoglobulin, and also delayed the deterioration of imaging changes.

CONCLUSION

IGU inhibits immunoglobulin secretion by B cells to relieve pulmonary inflammation and fibrosis. IGU also plays a protective role in the lung in ILD.

摘要

目的

本研究旨在探讨来氟米特(IGU)对博莱霉素(BLM)诱导的间质性肺疾病(ILD)的影响。

方法

通过气管内注射 BLM 建立肺纤维化模型组小鼠。将小鼠随机分为两组:(1)对照组(BLM 组)-气管内 BLM(BLM,3.5mg/kg,Kayaku,日本)+腹腔注射生理盐水,和(2)BLM+IGU 组-气管内 BLM(同对照组)+腹腔注射 IGU(50mg/kg/d)。在注射后第 7、14、21 和 28 天进行肺泡灌洗、组织病理学/免疫组织化学、影像学等检查。

结果

IGU 改善了包括顺应性(Crs)、组织阻尼(G)、静态顺应性(Cst)、吸气量(IC)、弹性阻力(Ers)、组织弹性(H)和呼吸系统阻力(Rrs)在内的肺功能。IGU 减轻了 BLM 诱导的肺纤维化和肺炎症变化,组织学检查显示。IGU 还减少了 BLM 引起的肺胶原产生和炎症损伤。IGU 通过抑制 B 细胞和免疫球蛋白的产生,减少了 BLM 诱导的肺纤维化小鼠中免疫球蛋白 IgG 和 I 型胶原的表达,也延迟了影像学变化的恶化。

结论

IGU 通过抑制 B 细胞分泌免疫球蛋白来缓解肺炎症和纤维化。IGU 在 ILD 中对肺也有保护作用。

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