Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People's Republic of China.
Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People's Republic of China.
Int Immunopharmacol. 2020 Apr;81:106205. doi: 10.1016/j.intimp.2020.106205. Epub 2020 Feb 9.
Graft-versus-host disease (GVHD) causes significant mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Berberine (BBR) is primarily used to alleviate inflammation caused by autoimmune disorders. Herein the effect of BBR and cyclosporine A (CsA) on GVHD prevention in murine models is explored. Acute GVHD was induced by total body irradiation and tail vein injection with the mixture of bone marrow cells and spleen lymphocytes. Then models were treated with BBR (10 mg/kg), CsA (5 mg/kg) or the combination of BBR and CsA (10 mg/kg and 5 mg/kg) once a day for 10 days. The survival rate, weight loss and GVHD index were monitored. Then the histological changes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, apoptosis and the levels of inflammatory cytokines, oxidative stress and nuclear factor-κB (NF-κB) signaling in liver and intestine were analyzed. Moreover, the levels of inflammatory cytokines and oxidative stress, and the count of T helper 1 (Th1) cells and Th17 cells in peripheral blood were determined. The results showed that BBR reduced GVHD-induced weight loss and GVHD index scores, attenuated liver and intestinal injury, and inhibited ALT and AST activities, inflammation, oxidative stress and NF-κB activation in liver and intestine. Additionally, BBR inhibited inflammation and reduced Th1 cell counts but had no effect on Th17 cell counts. Interestingly, the concomitant therapy of BBR and CsA was more potent than either BBR or CsA and effectively elevated the survival rate of GVHD models. This present study provides a new therapeutic strategy for alleviation of acute GVHD.
移植物抗宿主病（GVHD）是异基因造血干细胞移植（allo-HSCT）后导致死亡的主要原因。小檗碱（BBR）主要用于减轻自身免疫性疾病引起的炎症。本文旨在探讨 BBR 和环孢素 A（CsA）对小鼠模型 GVHD 预防的作用。通过全身照射和尾静脉注射骨髓细胞和脾淋巴细胞混合物诱导急性 GVHD。然后，用 BBR（10mg/kg）、CsA（5mg/kg）或 BBR 和 CsA（10mg/kg 和 5mg/kg）联合治疗模型，每天一次，共 10 天。监测存活率、体重减轻和 GVHD 指数。然后分析肝脏和肠道的组织学变化、丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）活性、细胞凋亡以及炎症细胞因子、氧化应激和核因子-κB（NF-κB）信号通路的水平。此外，还测定了外周血中炎症细胞因子和氧化应激水平以及辅助性 T 细胞 1（Th1）和 Th17 细胞的计数。结果表明，BBR 减轻了 GVHD 诱导的体重减轻和 GVHD 指数评分，减轻了肝脏和肠道损伤，并抑制了肝脏和肠道中 ALT 和 AST 活性、炎症、氧化应激和 NF-κB 激活。此外，BBR 抑制了炎症并减少了 Th1 细胞计数，但对 Th17 细胞计数没有影响。有趣的是，BBR 和 CsA 的联合治疗比单独使用 BBR 或 CsA 更有效，可有效提高 GVHD 模型的存活率。本研究为缓解急性 GVHD 提供了一种新的治疗策略。
