| 许杰,周雅丽,王文,何杨.重组人ADAMTS13通过调节炎症和氧化应激水平改善放射性肠损伤[J].中华放射医学与防护杂志,2022,42(6):416-421 |
| 重组人ADAMTS13通过调节炎症和氧化应激水平改善放射性肠损伤 |
| Recombinant human ADAMTS13 ameliorates radiation-induced intestinal injury by regulating inflammation and oxidative stress |
| 投稿时间：2022-01-25 |
| DOI：10.3760/cma.j.cn112271-20220125-00033 |
| 中文关键词: 重组人血管性血友病因子裂解蛋白酶 放射 肠损伤 炎症 氧化应激 |
| 英文关键词:rhADAMTS13 Radiation Intestinal injury Inflammation Oxidative stress |
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| 中文摘要: |
| 目的 研究重组人血管性血友病因子裂解蛋白酶(rhADAMTS13)对放射性肠损伤的防护效应。方法 将30只C57BL/6 J小鼠按随机数表法分为健康对照组、12 Gy腹部照射组(单纯照射组)和rhADAMTS13联合12 Gy照射组(联合组)，分别为6、12和12只。联合组于照射前3 d给予2.5 μg/kg rhADAMTS13尾静脉注射，单纯照射组和联合组给予单次12Gy X射线腹部照射。于照射后1和3 d处死，酶联免疫吸附法(ELISA)检测血浆血管性血友病因子(vWF)、血管性血友病因子裂解蛋白酶(ADAMTS13)和C-反应蛋白(CRP)的水平，苏木素-伊红(HE)染色观察肠组织病理学改变，免疫组织化学染色检测肠组织Ki67、TNF- α和MPO表达水平，生化试剂盒检测血浆丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性和总抗氧化能力(T-AOC)。结果 与健康对照组比较，单纯照射组照射后1(1.38±0.11)和3 d(1.70±0.10)小鼠血浆vWF水平增高(t=6.20、12.29，P < 0.05)，ADAMTS13水平降低(t=9.82、22.83，P < 0.05)；与单纯照射组比较，联合组照射后1(1.23±0.12)和3 d(1.48±0.09)小鼠血浆vWF水平减低(t=2.93、3.96，P < 0.05)，ADAMTS13水平升高(t=5.09、9.82，P < 0.05)。与单纯照射组比较，照射后3 d联合组绒毛长度缩短程度明显降低(t=8.51，P < 0.05)，免疫组织化学染色显示，联合组照射后3 d隐窝Ki67+细胞数量明显增加(t=9.82，P < 0.05)，TNF- α和MPO浸润程度明显降低(t=15.44、14.33，P < 0.05)。此外，rhADAMTS13干预能显著降低照射后1和3 d小鼠血浆CRP(t=5.02、2.96，P < 0.05)和MDA(t=2.47、2.55，P < 0.05)的含量，并增加SOD活性(t=2.64、5.64，P < 0.05)和T-AOC(t=3.05、5.07，P < 0.05)。结论 rhADAMTS13能够通过降低炎症和氧化应激水平减轻电离辐射所致小鼠肠损伤，为放射性肠损伤的防护提供了一种新的策略。 |
| 英文摘要: |
| Objective To study the protective effect of recombinant human ADAMTS13 (rhADAMTS13) on radiation-induced intestinal injury.Methods Thirty C57BL/6 J mice were randomly divided into healthy control group, 12 Gy abdominal irradiation group (simple irradiation group) and rhADAMTS13 combined with 12 Gy irradiation group (combined group) with 6, 12 and 12 mice per group. The combined group was given 2.5 μg/kg rhADAMTS13 via tail vein injection 3 d before irradiation. 12 Gy X-ray abdominal irradiation was given to the simple irradiation group.The mice were executed at 1 and 3 d after irradiation, and plasma vWF, ADAMTS13 and CRP concentrations were measured by enzyme-linked immunosorbent assay (ELISA).Intestinal histopathological changes were observed by hematoxylin-eosin (HE) staining.Intestinal Ki67, TNF- α and MPO expression levels were detected by immunohistochemical staining.Plasma malondialdehyde (MDA), superoxide dismutase (SOD) activity and total antioxidant capacity (T-AOC) were measured by biochemical kits.Results Compared with the healthy control group, the plasma vWF level was increased(t=6.20、12.29, P < 0.05) and ADAMTS13 level was decreased(t=9.82、22.83, P < 0.05)in mice at 1(1.38±0.11)and 3 (1.70±0.10)after irradiation.Compared with the simple irradiation group, the plasma vWF level was reduced (t=2.93, 3.96, P < 0.05) and ADAMTS13 level was increased (t=5.09, 9.82, P < 0.05) in mice at 1 (1.23±0.12) and 3d(1.48±0.09) after irradiation in the combined group. Immunohistochemical staining showed that the number of Ki67+ cells in the crypt of the combined group increased significantly (t=9.82, P < 0.05) and the degree of TNF-α and MPO infiltration decreased significantly (t=15.44, 14.33, P < 0.05) compared with the simple irradiation group.In addition, rhADAMTS13 intervention significantly reduced plasma CRP (t=5.02, 2.96, P < 0.05) and MDA (t=2.47, 2.55, P < 0.05), but increased SOD activity (t=2.64, 5.64, P < 0.05) and T-AOC (t=3.05, 5.07, P < 0.05).Conclusions rhADAMTS13 attenuates radiation-induced intestinal injury in mice by reducing the levels of inflammation and oxidative stress, providing a new strategy for the protection of radiation-induced intestinal injury. |
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