| 何秀兰,罗治彬.麦冬皂苷D对小鼠放射性肺损伤的防护作用及机制[J].中华放射医学与防护杂志,2023,43(4):248-255 |
| 麦冬皂苷D对小鼠放射性肺损伤的防护作用及机制 |
| Protective effect and mechanism of ophiopogonin D on radiation-induced lung injury in mice |
| 投稿时间：2022-09-12 |
| DOI：10.3760/cma.j.cn112271-20220912-00370 |
| 中文关键词: 麦冬皂苷D 放射性肺损伤 氧化应激 凋亡 p53 |
| 英文关键词:Ophiopogonin D Radiation induced lung injury Oxidative stress Apoptosis p53 |
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| 中文摘要: |
| 目的 探索麦冬皂苷D对小鼠放射性肺损伤的防护作用及其机制。方法 60只C57BL/6雌性小鼠按随机抽样法分为4组:健康对照组、单纯照射组、照射+麦冬皂苷D组、照射+地塞米松组,每组15只。用6 MV X射线15 Gy单次照射小鼠。于照射前3 d开始,照射+麦冬皂苷D组给予10 mg/kg麦冬皂苷D溶液腹腔注射,照射+地塞米松组给予10 mg/kg地塞米松溶液腹腔注射,健康对照组和单纯照射组给予生理盐水腹腔注射,每日1次,至照后1周。于照射后3 d、1周、6周取材,苏木精-伊红(HE)染色法和Masson染色法观察肺组织病理学变化,免疫组织化学法观察8-羟基脱氧鸟苷(8-OHdG)、p53、p53上调凋亡因子(PUMA)、半胱氨酸天冬氨酸蛋白水解酶3(Caspase-3)、Ⅰ型胶原纤维(Collagen Ⅰ)、Ⅲ型胶原纤维(Collagen Ⅲ)表达,蛋白提取及免疫印迹实验(Western blot)法进一步验证凋亡相关蛋白p53、PUMA、Caspase-3的表达,酶联免疫吸附试验(ELISA)检测转化生长因子β1(TGF-β1)和白介素6(IL-6)的表达。结果 照后1周,麦冬皂苷D能减轻肺组织的出血、渗出、水肿、炎症浸润,降低了照射后肺组织8-OHdG、p53、PUMA、caspase-3氧化应激及凋亡相关蛋白的表达(t=8.39、12.60、5.92、7.00,P＜0.05)。在照后3 d、1周、6周,麦冬皂苷D降低了小鼠血液中TGF-β1(t=9.32、8.97、6.83,P＜0.05)和IL-6(t=8.22、7.80、8.28,P＜0.05)的表达。在照射后6周,麦冬皂苷D可减轻肺间质的Collagen Ⅰ、Collagen Ⅲ生成(t=6.41、7.50,P＜0.05)。结论 麦冬皂苷D对放射性肺损伤有防护作用,可缓解放射性肺炎和肺纤维化早期的胶原沉积,其作用机制可能是通过减轻机体氧化应激,减少炎症相关因子的表达,抑制肺组织细胞凋亡,从而抑制胶原产生。 |
| 英文摘要: |
| Objective To investigate the protective effect and mechanism of ophiopogonin D on lung injury induced by radiation in mice.Methods A total of 60 female C57BL/6 mice were randomly divided into 4 groups: control group, irradiation group, irradiation+ophiopogonin D group and irradiation+dexamethasone group, with 15 mice in each group. The mice were irradiated with a single dose of 6 MV X-rays of 15 Gy. Three days before irradiation, the mice in irradiation+ophiopogonin D group were intraperitoneally injected with 10 mg/kg ophiopogonin D solution. The mice in irradiation+dexamethasone group were intraperitoneally injected with 10 mg/kg dexamethasone solution. The mice in control group and irradiation group were intraperitoneally injected with normal saline once a day until 1 week after irradiation. Tissue samples were collected at 3 d, 1 week, and 6 weeks post-irradiation. Hematoxylin-eosin (HE) staining and Masson's trichrome staining were used to observe the pathological changes of lung tissue. The expressions of 8-hydroxy-deoxyguanosine (8-OHdG), p53, p53 up-regulated apoptosis factor (PUMA), cysteine aspartate proteolytic enzyme-3 (caspase-3), Collagen Ⅰ and Collagen Ⅲ were observed by immunohistochemistry. Western blot was used to verify the expressions of apoptosis related proteins including p53, PUMA and caspase-3.Results HE staining of lung tissue showed that ophiopogonin D could reduce hemorrhage, exudation, edema and inflammatory infiltration in lung tissue 1 week post irradiation. Moreover, ophiopogonin D reduced the expression of 8-OHdG (t=8.39, P < 0.05), the oxidative stress, and the expressions of p53, PUMA, caspase-3 apoptosis-related proteins (t=12.60, 5.92, 7.00, P < 0.05), and inhibited the apoptosis of alveolar epithelial cells and alleviated other damage in the irradiated lung tissue 1 week post-irradiation. Ophiopogonin D also reduced collagen deposition in lung tissue 6 weeks after irradiation, and reduced the expression of transforming growth factor (TGF-β1) (t=9.32, 8.97, 6.83, P < 0.05) and interleukin-6 (t=8.22, 7.80, 8.28, P < 0.05) in the blood of mice at 3 d, 1 week, and 6 weeks after irradiation. At 6 weeks after exposure,ophiopogonin D reduced the production of Collagen Ⅰ and Collagen Ⅲ in the lung interstitium (t=6.41, 7.50, P < 0.05), and alleviated the pulmonary fibrosis in the late stage of radiation.Conclusions Ophiopogonin D has protective effects on lung injury caused by radiation, including the alleviation of early radiation pneumonia and late pulmonary fibrosis, by reducing oxidative stress, the expression of inflammation-related factors, apoptosis of lung tissue, and collagen production. |
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