| 周鹏飞,李卓成,朱昱蒙,刘红娇,冯 转.CyPA抗体治疗对博来霉素诱导的小鼠系统性硬化症的影响研究[J].,2024,(23):4401-4407 |
| CyPA抗体治疗对博来霉素诱导的小鼠系统性硬化症的影响研究 |
| Study on the Effect of CyPA Antibody Therapy on Bleomycin-induced Systemic Sclerosis in Mice |
| 投稿时间：2024-04-25 修订日期：2024-05-20 |
| DOI：10.13241/j.cnki.pmb.2024.23.001 |
| 中文关键词: CyPA 系统性硬化症 炎性细胞因子 |
| 英文关键词: CyPA Systemic sclerosis Inflammatory cytokine |
| 基金项目:陕西省创新能力支撑计划（2023-CX-PT-18） |
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| 中文摘要: |
| 摘要 目的：探索CyPA抗体治疗博来霉素诱导的小鼠系统性硬化症的效果。方法：通过BLM诱导系统性硬化症小鼠模型，生理盐水组小鼠作为对照组，系统性硬化症小鼠随机分为早期治疗组和末期治疗组，早期治疗组分别于造模第8、15、22天尾静脉注射10 mg/kg CyPA抗体1次，末期治疗组于造模第22天尾静脉注射10 mg/kg CyPA抗体1次。HE染色和Masson染色观察系统性硬化症小鼠皮肤组织病变，组织化学染色法检测小鼠皮肤组织中α平滑肌肌动蛋白（α-SMA）、TGF-β以及炎性因子CyPA、白细胞介素1（IL-1β）、IL-6的表达水平。Olink mouse exploratory panel检测小鼠血清细胞因子IL-17α、TGF-β、整合素亚基β6（ITG-β6）、TNF受体超家族成员11B（TNFRSF11b）、IL-6、IL-1α、IL-1β、IL-10、TNF、CC趋化因子配体5（CCL5）、CXC趋化因子配体9（CXCL9）、烟酰胺腺嘌呤二核苷酸激酶（NADK）、促红细胞生成素（EPO）、集落刺激因子2（CSF2）水平。结果：与对照组相比，BLM组小鼠注射部位皮肤真皮层增厚，皮肤胶原增多；早期治疗组小鼠上述表现有显著缓解。与对照组相比，BLM组小鼠血浆中促炎因子IL-1β、IL-6和CyPA浓度明显上调，疾病早期阶段CyPA抗体干预治疗效果显著，早期治疗显著降低上述因子浓度水平，表明小鼠炎症明显缓解。并且早期治疗组病变组织α-SMA和TGF-β表达水平均呈下降趋势，表明胶原蛋白聚集减少，组织病变明显缓解。结论：早期炎症阶段，CyPA抗体可通过减少炎性细胞因子IL-1β、IL-6分泌有效缓解小鼠系统性硬化症疾病进程。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the effects of neutralizing CyPA antibody blocking therapy in course of systemic sclerosis induced by bleomycin (BLM) in mice, and to clarify the effects of neutralizing CyPA antibody on the process of systemic sclerosis in mice. Methods: Bleomycin induced systemic sclerosis model was adopted. The mice were divided into control group, BLM group, early treatment group (CyPA antibody or control IgG was used for treatment on day 1, 8, 15, 22 in the mice model of systemic sclerosis induced by BLM) and late treatment group (CyPA antibody or control IgG was used for treatment on day 22 in the mouse model of systemic sclerosis induced by BLM). HE staining and Masson staining were used to observe the skin lesions of mice with systemic sclerosis. The expression levels of α smooth muscle actin (α-SMA), TGF-β, and inflammatory factors CyPA, interleukin 1β (IL-1β), IL-6 in the skin tissues of mice were detected by histochemical staining. The expression levels of serum cytokines including IL-17α, TGF-β, integrin beta 6 (ITG-β6), TNF receptor superfamily member 11B (TNFRSF11b), IL-6, IL-1α, IL-1β, IL-10, TNF, CC-chemokine ligand 5 (CCL5), CXC chemokine ligand 9 (CXCL9), nicotinamide adenine dinucleotide kinase (NADK), erythropoietin (EPO), colony stimulating factor 2 (CSF2) in serum were detected by Olink mouse exploratory panel. Results: Compared with that in the control group, the skin dermis of BLM group was thickened, and the skin collagen increased. The pathological lesions were alleviated in the early treatment group compared with that in the BLM group. Compared with that in the control group, the plasma concentrations of pro-inflammatory factors IL-1β, IL-6, and CyPA in BLM group significantly upregulated. In the early stage of systemic sclerosis, neutralizing CyPA antibody intervention treatment had a significant effect accompanied by decreasing the expression of IL-1β, IL-6, and CyPA, indicating that the inflammation was significantly alleviated. In addition, the expression levels of α-SMA and TGF-β decreased significantly, which illustrated collagen aggregation and tissue lesions were significantly alleviated. Conclusion: In the early stage of inflammation, neutralizing CyPA antibody blocking therapy can effectively alleviate the progression of systemic sclerosis in mice by reducing the secretion of inflammatory cytokines IL-1β and IL-6. |
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