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Objective To evaluate the protective effect and the underlying mechanism of mesenchymal stem cell-derived extracellular vesicle (MSC-EV) on radiation-induced liver injury and liver cell line injury in mouse models. Methods C57BL/6 mice were randomly divided into the blank group, model group and MSC-EV treatment group (treatment group), with 9 mice in each group. AML12 cells were randomly divided into the control group, irradiation group and MSC-EV intervention group (intervention group). Animal and cell models with radiation-induced injury were established by one-time 15 Gy and 6 Gy X-ray irradiation, respectively. At 48 h after irradiation, liver tissues and serum samples of mice were collected and prepared for subsequent experiments. At 15 h post-irradiation, cell experiment was carried out. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and content of malondialdehyde (MDA) in liver tissues and cells were measured. The relative expression levels of interleukin (IL)-1β, IL-6, transforming growth factor (TGF)-β and CXC chemokine ligand (CXCL)10 messenger RNA (mRNA) were detected by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). Liver tissues were prepared for hematoxylin-eosin (HE) staining to calculate liver pathological injury score. The apoptosis of liver tissues and cells was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and propidiumiodide (PI) staining, respectively. The expression levels of glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1) proteins were detected by Western blot. The production level of reactive oxygen species (ROS) was detected by dihydroethidine (DHE) staining. The fluorescence intensity of mitochondrial permeability transition pore (mPTP) was determined. Results Compared with the blank group, serum levels of AST and ALT were up-regulated, and the relative expression levels of IL-1β, TGF-β and CXCL10 mRNA in the mouse liver tissues were up-regulated, and MDA content was increased, liver injury score was elevated, cell apoptosis rate was increased, intracellular ROS level was elevated, and the relative expression levels of GPX4 and FSP1 proteins in the mouse liver tissues were down-regulated in the model group, and the differences were statistically significant (all P<0.05). Compared with the model group, serum levels of AST and ALT were decreased, and the relative expression levels of IL-1β, TGF-β and CXCL10 mRNA in the liver tissues of mice were down-regulated, MDA content was declined, liver injury score was declined, cell apoptosis rate was decreased, intracellular ROS level was decreased, and the relative expression levels of GPX4 and FSP1 proteins in the liver tissues of mice were up-regulated in the treatment group, and the differences were statistically significant (all P<0.05). Compared with the control group, cell apoptosis rate was increased, intracellular ROS level was elevated, the fluorescence intensity of mPTP was weakened, the relative expression levels of IL-1β, TGF-β and IL-6 mRNA were up-regulated, MDA content was increased, and the relative expression levels of GPX4 and FSP1 proteins were down-regulated in the irradiation group, and the differences were statistically significant (all P<0.05). Compared with the irradiation group, cell apoptosis rate was declined, intracellular ROS level was decreased, the fluorescence intensity of mPTP was strengthened, the relative expression levels of IL-1β, TGF-β and IL-6 mRNA were down-regulated, MDA content was decreased and the relative expression levels of GPX4 and FSP1 proteins were up-regulated in the intervention group, and the differences were statistically significant (all P<0.05). Conclusions MSC-EV may effectively alleviate radiation-induced liver injury by reducing ferroptosis of liver cells, enhancing antioxidant level and decreasing the production of lipid peroxide, thereby effectively alleviating radiation-induced liver injury.
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Objective To evaluate early diagnostic value of quantitative analysis of contrast-enhanced ultrasound (CEUS) in acute radiation-induced liver injury.Methods Sixty female rats were divided into two groups:50 rats in an experimental group (model group) and 10 rats in a negative control group.The rats in model group were radiated with stereotactic single dose of 20Gy on their liver to establish acute radiationinduced liver injury models.Each 10 rats from model groups and 2 rats from control group were randomly selected and underwent CEUS and histopathological examination on the 3,7,14,21,28 days after radiation.The degree of injury was classified into four groups according to pathological grading:non-injured group,mild injured group,moderated injured group and severe injured group.The dynamic images of CEUS were off-line analysis and the parameters of arrival time of contrast agent to hepatic artery (HAAT),the arrival time of contrast agent to hepatic vein (HVAT),and the transit time of hepatic artery-hepatic vein (HAHVTT) were recorded.Time intensity curve (TIC) of liver parenchyma drawn by the software of quantitative analysis was used to obtain quantitative parameters including time to peak (TTP) and peak intensity (PI).Results Along with the severity degree of radiation-induced liver injury,the quantitative parameters,PI decreased while TTP extended.PI of mild injured group,moderated injured group and severe injured group were lower than that of non-injured group (P ＜0.05).TTP of the three liver injuried groups was higher than non-injured group (P ＜0.05).The quantitative parameters HA-HVTT of moderated injured group and severe injured group were decreased than the non-injured group (P ＜0.05),whereas the difference between mild injured group and non-injured group was not significant.Conclusions Quantitative analysis of CEUS can provide a certain value for early diagnosis in acute radiation-induced liver injury.
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@#Objective To explore the establishment of a rat model of acute radiation-induced liver injury and sig-nificance of the dynamic changes of TGF-β1 expression.Methods Forty healthy 6-week old male SD rats were randomly divided into model group (n=30) and control group (n=10).The right liver of rats in the model group was given a single dose of 25 Gy 6 MV X-ray irradiation.Histopathological examination using HE staining and transmission electron microsco-py were conducted to observe the liver pathological changes in rats at 3, 5, and 10 days after irradiation, serum TGF-β1 was detected, and relevant indicators of liver function ( ALT, AST, ALP) were determined.Statistical analysis was per-formed using SPSS 17.0 software.Results At 3, 5 and 10 days after irradiation, early pathological changes in the liver cells were observed by electron microscopy, the expression of TGF-β1 was gradually increased with the time prolongation, and significant differences were found between the model group and the control group at different time points (P<0.05). The light microscopic observation of liver tissues did not show significant differences between the control group and model group.The liver ALT, AST, ALP at different time points did not show significant differences between the two groups ( P>0.05).Conclusion Electron microscopy can be used to evaluate the early changes of radiation-induced liver injury, pri-or to the alterations visible by routine light microscopy.TGF-β1 can be used to predict the degree of radiation-induced liver injury, and may be used as a sensitive serum cytokine in predicting the degree of radiation-induced acute liver injury.
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Objective Investigate the Protective effect of paeoniflorin in rats with acute liver injury. Methods Male SD rats were randomly divided into normal group, model group, paeoniflorin in small, middle and high dose group (20 mg/kg, 40 mg/kg, 80 mg/kg), paeony glycoside group (50 mg/kg). Except normal group, the rest of groups were irradiated fractionally by VARIN 21-EX linear accelerator at right liver, The paeoniflorin group and paeony glycoside group were lavaged everyday after irradiation for corresponding drugs and doses. Normal group and model group give equal volume normal saline everyday. All rats were killed on 2nd and 4th weekend. Measure rats serum AST, ALT, hepatic tissue GSH, SOD, and HE staining score. Results The rats in model group liver tissue HE staining scores increased to(2.25±0.53)on 2nd weekend, The serum levels of AST, ALT increased to(112.83±19.20)U/L, (80±21.97)U/L, it significantly increased Compared with the normal group(63.06±7.15)U/L, (42.30±4.45)U/L, P<0.01. The liver GSH contents of paeoniflorin in each dosage groups rats were(60.89±8.43)U/mg, (67.84±9.05)U/mg, (71.92±8.11)U/mg on 2 nd weekend, Compared with the model group(37.32±11.25)U/mg, (90.54±12.12)U/mg, P<0.05或<0.01. Conclusions The irradiated rats go into acute liver injury on 2nd weekend, paeoniflorin has protective effect on acute liver injury in rats.
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In this study, the time-dependent changes on dynamic computed tomograph (CT) of radiation-induced liver injury in gastric cancer patients was examined. The CT images of 52 gastric cancer patients who had received chemoradiotherapies were reviewed on the PACS system. Dynamic CT scan was performed in all the subjects. Our results showed that 18 patients were found to have radiation-induced liver injury. The CT findings of radiation-induced liver injury in gastric cancer patients tend to show up one month after radiation treatment. The damaged area was of low density on all three phases, and then it was enhanced on portal vein phase or delay phase. The focal radiation reaction of liver without basic disease vanished 9-11 months later after treatment. We are led to conclude that dynamic CT is of help in the diagnosis of CRT-induced liver injury, and it may be the method of choice for following up the whole course of the CRT-induced liver injury, i.e., form hepatic damage to healing. The classification of CT findings we recommend can avoid the influence of technological factors, and thereby serve as a better guide for treatment of CRT-induced liver injury.
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Objective To investigate the role of mesenchymal stem cells in the repair of radiation induced liver injury.Methods 12 female SD rats were irradiated with 20 Gy 6 MV X-rays on the right lobe of the liver,to establish the model of radiation induced liver injury.The rats were divided randomly into two groups as invention group and control group,and transplanted with 1 ml male mesenchymal suspension or 1 ml normal saline in 4 hours after radiotherapy.The morphological changes of liver were observed.The existence of sex determining gene Y(SRY)and the level of alpha-smooth muscle actin (a-SMA) were detected.Results Some injury of right lobe liver in two groups were observed,and the injury degree of right lobe liver in intervention group were lower than that of control group.The amount of SRY positive cells in the right lobe liver of intervention group was higher than that in the left lobe liver(t ＝ 3.77,P ＜0.05).The positive expression rate of a-SMA in right lobe liver of intervention group was lower than that of control group.Conclusions Acute radiation induced liver injury could lead BMSCs＇ homing in order to decrease the degree of liver fibrosis.