Fu Xiaobin, Li Tingting, Yao Qiwei
Department of Radiation Oncology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.
Department of Radiation Oncology, Fujian Medical University Cancer Hospital & Fujian Cancer Hospital, Fuzhou, China.
Front Oncol. 2022 Mar 30;12:811183. doi: 10.3389/fonc.2022.811183. eCollection 2022.
The aim of this study was to assess and update the protective effects and underlying mechanisms of Ophiopogonin C (OP-C), a biologically active component separated and purified from , in ameliorating radiation-induced pulmonary fibrosis in C57BL/6 mice administered thoracic radiation.
We randomly divided 75 mice into five groups and administered a dose of 12-Gy whole thoracic radiation to establish a pulmonary fibrosis animal model. Mice were treated with OP-C or dexamethasone combined with or without cephalexin by daily gavage for 4 weeks. All mice were sacrificed after the completion of thoracic irradiation at 28 weeks. Serum levels of interleukin-6 and transforming growth factor-β1 (TGF-β1) were evaluated. Moreover, superoxide dismutase (SOD) levels in lung tissue were measured. The severity of fibrosis was evaluated using the hydroxyproline content of the lung tissue. The pathological changes in the five groups were detected by hematoxylin and eosin and Masson trichrome staining. Smooth muscle actin expression was detected using immunohistochemical staining. Matrix metalloproteinases-2 (MMP-2) and tissue inhibitors of metalloproteases-2 (TIMP-2) were examined by immunohistochemical staining of the lung sections, and semiquantitative analysis was used to calculate the expression of MMP-2 and TIMP-2.
Irradiated mice treated with OP-C or DXE combined with or without cephalexin significantly reduced mortality in mice and fibrosis levels by 1) reducing the deposition of collagen and accumulation of inflammatory cells and fibroblasts, 2) downgrading levels of the promote-fibrosis cytokine TGF-β1, and 3) increasing SOD activity in the lung tissue compared with that of irradiated mice without treatment. However, there were no statistical differences in fibrosis levels among the irradiated mice treated with OP-C or DXE combined with or without cephalexin.
OP-C significantly ameliorates radiation-induced pulmonary fibrosis and may be a promising therapeutic strategy for this disorder.
本研究旨在评估并更新从麦冬中分离纯化得到的生物活性成分麦冬皂苷C（OP-C）对接受胸部放疗的C57BL/6小鼠放射性肺纤维化的保护作用及其潜在机制。
我们将75只小鼠随机分为五组，给予12 Gy的全胸照射以建立肺纤维化动物模型。通过每日灌胃给予小鼠OP-C或地塞米松（联合或不联合头孢氨苄），持续4周。在28周完成胸部照射后处死所有小鼠。评估血清白细胞介素-6和转化生长因子-β1（TGF-β1）水平。此外，测量肺组织中超氧化物歧化酶（SOD）水平。使用肺组织羟脯氨酸含量评估纤维化严重程度。通过苏木精-伊红染色和Masson三色染色检测五组的病理变化。使用免疫组织化学染色检测平滑肌肌动蛋白表达。通过肺切片免疫组织化学染色检查基质金属蛋白酶-2（MMP-2）和金属蛋白酶组织抑制剂-2（TIMP-2），并采用半定量分析计算MMP-2和TIMP-2的表达。
与未治疗的照射小鼠相比，接受OP-C或地塞米松联合或不联合头孢氨苄治疗的照射小鼠通过以下方式显著降低了小鼠死亡率和纤维化水平：1）减少胶原蛋白沉积以及炎症细胞和成纤维细胞的积聚；2）降低促纤维化细胞因子TGF-β1的水平；3）增加肺组织中的SOD活性。然而，接受OP-C或地塞米松联合或不联合头孢氨苄治疗的照射小鼠之间的纤维化水平无统计学差异。
OP-C可显著改善放射性肺纤维化，可能是治疗该疾病的一种有前景的策略。
