Xu Jie,Zhou Yali,Wang Wen,et al.Recombinant human ADAMTS13 ameliorates radiation-induced intestinal injury by regulating inflammation and oxidative stress[J].Chinese Journal of Radiological Medicine and Protection,2022,42(6):416-421
Recombinant human ADAMTS13 ameliorates radiation-induced intestinal injury by regulating inflammation and oxidative stress
Received:January 25, 2022  
DOI:10.3760/cma.j.cn112271-20220125-00033
KeyWords:rhADAMTS13  Radiation  Intestinal injury  Inflammation  Oxidative stress
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Author NameAffiliationE-mail
Xu Jie MOH Key Lab of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China  
Zhou Yali MOH Key Lab of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China  
Wang Wen MOH Key Lab of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China  
He Yang MOH Key Lab of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China heyang1963@163.com 
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Abstract::
      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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