研究动态
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利妥昔单抗阻断 CD20 细胞会延迟大鼠口腔创伤性溃疡的伤口愈合。

CD20 + cells blockage by rituximab delays wound healing in oral traumatic ulcers in rats.

发表日期:2023 Nov 08
作者: Antonio Alexandre Coelho, Rute Romão Carvalho, Ana Luiza Muniz, André Alves Crispim, Anderson Maia Meneses, Carla Welch da Silva, Dayrine Silveira de Paula, Ana Paula Negreiros Nunes Alves, Fabrício Bitu Sousa, Paulo Goberlânio de Barros Silva
来源: CYTOKINE & GROWTH FACTOR REVIEWS

摘要:

口腔创伤性溃疡(OTU)的伤口愈合与细胞因子和炎症细胞密切相关,抗炎细胞(例如淋巴细胞B)的减少可能会干扰OTU修复。我们的目的是评估 CD20 细胞在大鼠 OTU 愈合过程中的作用。将 Wistar 雄性大鼠分为四组:对照组(用 0.1 mL/kg 盐水治疗)和三组用抗 CD20 利妥昔单抗治疗(在 OTU 生产前 24 小时,以 2.5、10 或 40 mg/kg RTX)。在溃疡后第3、7、14和21天对动物进行称重(第0天)并实施安乐死。通过血细胞(血液学分析)和创伤性溃疡进行临床测量。对粘膜样本进行组织学检查(分数 0-4)、组织化学检查(胶原蛋白测定(苦天狼星))、组织形态计量学检查(细胞计数)和免疫组织化学检查(CD20、肿瘤坏死因子 α(TNF-α)、白细胞介素 (IL)-1β、IL) -6 和 α-平滑肌肌动蛋白 (α-SMA)) 进行了分析。进行 ANOVA-1-2-way/Bonferroni、Kruskal-Wallis/Dunn 和相关分析(GraphPad Prism 5.0,p < 0.05)。RTX 导致白细胞减少、淋巴细胞减少和中性粒细胞减少(p < 0.001),高剂量可减少OTU 面积 (p = 0.001)、组织学评分受损 (p < 0.05)、延迟多形核细胞 (p < 0.001) 和单核细胞 (p < 0.001)、总细胞数 (p = 0.011)、I 型细胞 (p = 0.008) ) 和 III 型胶原 (p = 0.021)。RTX 治疗减少了 OTU (p = 0.001)、TNF-α (p = 0.006) 和 α-SMA (p = 0.022) 免疫染色中的 CD20 细胞并延迟了 IL-6减少 (p = 0.006),对 IL-1β 免疫染色没有影响。 RTX 阻断 CD20 细胞可减少 OTU 中的细胞迁移、急性炎症和伤口愈合。版权所有 © 2023 Elsevier Ltd。保留所有权利。
Wound healing of oral traumatic ulcers (OTU) is strongly associated with cytokines and inflammatory cells, and the reduction of anti-inflammatory cells, such as lymphocyte B, may interfere with OTU repair. We aimed to evaluate the role of CD20 + cells in the healing process of OTU in rats.Wistar male rats were divided into four groups: a control group (treated with 0.1 mL/kg of saline) and three groups treated with anti-CD20 rituximab (RTX) at 2.5, 10, or 40 mg/kg 24 h before OTU production. The animals were weighed (day 0) and euthanized on days 3, 7, 14, and 21 after ulceration. With Blood cells (hematological analysis) and the traumatically induced ulcers were clinically measured. The mucosal samples were histologically (scores 0-4), histochemically (collagen assay (picrosirius)), histomorphometrically (cell counting), and immunohistochemically (CD20+, Tumor Necrosis Factor alpha(TNF-α), Interleukin(IL)- 1β, IL-6 and α-smooth-muscle-actin (α-SMA)) analyzed. ANOVA-1-2-way/Bonferroni, Kruskal-Wallis/Dunn, and correlation analyses were performed (GraphPad Prism 5.0, p < 0.05).RTX leads to leukopenia, lymphocytopenia, and neutropenia (p < 0.001), and high doses reduced the OTU area (p = 0.001), impaired histologic scores (p < 0.05), and delayed polymorphonuclear (p < 0.001) and mononuclear (p < 0.001) cells, and total (p = 0.011), type-I (p = 0.008), and type-III (p = 0.021) collagen.RTX treatment reduced CD20+ cells in OTU (p = 0.001), TNF-α (p = 0.006), and α-SMA (p = 0.022) immunostaining and delayed IL-6 reduction (p = 0.006), with no influence in IL-1β immunostaining. CD20 + cell blockage by RTX reduced cell migration, acute inflammation, and wound healing in OTU.Copyright © 2023 Elsevier Ltd. All rights reserved.