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Objective To investigate the value of 18F-fluorodeoxyglucose (FDG) PET/CT imaging and cardiac MRI (CMR) in the diagnosis of radiation-induced heart disease (RIHD) in Beagle models.Methods Twenty-four normal male Beagle dogs (1-year old) were randomly divided into control group and irradiated groups (3-month,6-month and 12-month after radiation).The left anterior myocardium of Beagle dogs in irradiated groups was irradiated locally with a single dose of 20 Gy X-ray.Cardiac 18F-FDG PET/CT imaging and CMR were performed on all dogs,and the mean standardized uptake value (SUVmax) and the area of lesions with increased 18F-FDG uptake were obtained.After imaging examinations were finished,dogs were sacrificed and their hearts were taken out to perform Masson staining and electron microcopy.Oneway analysis of variance was used for data analysis.Results There was basically no uptake in myocardium in control group.The myocardium showed increased uptake of 18F-FDG in the irradiated groups.The SUV of myocardium in 3-month,6-month and 12-month after radiation groups and control group were 5.90± 1.31,4.66±2.21,3.21±0.82 and 1.13±0.21,respectively (F=11.81,P＜0.05).The area with increased 18F-FDG uptake in the irradiated groups decreased progressively with the prolongation of irradiation time (F =195.74,P＜0.01).The reduction in myocardial perfusion and myocardial fibrosis were observed by CMR early at 6-month after irradiation.Compared with the control group,the 6-month and 12-month after radiation groups had increased end diastolic volume (EDV) and end systolic volume (ESV;F =15.479 and 16.908,both P＜0.01),and decreased left ventricular ejection fraction (LVEF;F=63.715,P＜0.01).The progressive aggravation of myocardial fibrosis was displayed in irradiated groups by Masson staining.The mitochondria degeneration,swelling and the count reduction in irradiated groups were observed by electron microscopy.Conclusions The increased 18F-FDG uptake in the irradiated myocardium may predict the risk of RIHD.18F-FDG PET/CT imaging can detect RIHD earlier than CMR.
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Objective@#To investigate the value of 18F-fluorodeoxyglucose (FDG) PET/CT imaging and cardiac MRI (CMR) in the diagnosis of radiation-induced heart disease (RIHD) in Beagle models.@*Methods@#Twenty-four normal male Beagle dogs (1-year old) were randomly divided into control group and irradiated groups (3-month, 6-month and 12-month after radiation). The left anterior myocardium of Beagle dogs in irradiated groups was irradiated locally with a single dose of 20 Gy X-ray. Cardiac 18F-FDG PET/CT imaging and CMR were performed on all dogs, and the mean standardized uptake value (SUVmean) and the area of lesions with increased 18F-FDG uptake were obtained. After imaging examinations were finished, dogs were sacrificed and their hearts were taken out to perform Masson staining and electron microcopy. One-way analysis of variance was used for data analysis.@*Results@#There was basically no uptake in myocardium in control group. The myocardium showed increased uptake of 18F-FDG in the irradiated groups. The SUVmean of myocardium in 3-month, 6-month and 12-month after radiation groups and control group were 5.90±1.31, 4.66±2.21, 3.21±0.82 and 1.13±0.21, respectively (F=11.81, P<0.05). The area with increased 18F-FDG uptake in the irradiated groups decreased progressively with the prolongation of irradiation time (F=195.74, P<0.01). The reduction in myocardial perfusion and myocardial fibrosis were observed by CMR early at 6-month after irradiation. Compared with the control group, the 6-month and 12-month after radiation groups had increased end diastolic volume (EDV) and end systolic volume (ESV; F=15.479 and 16.908, both P<0.01), and decreased left ventricular ejection fraction (LVEF; F=63.715, P<0.01). The progressive aggravation of myocardial fibrosis was displayed in irradiated groups by Masson staining. The mitochondria degeneration, swelling and the count reduction in irradiated groups were observed by electron microscopy.@*Conclusions@#The increased 18F-FDG uptake in the irradiated myocardium may predict the risk of RIHD. 18F-FDG PET/CT imaging can detect RIHD earlier than CMR.
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Objective To investigate the value of local myocardial blood flow and myocardial function parameters in monitoring the dynamic changes of radiation induced heart disease (RIHD) using 13NNH3 PET gated myocardial perfusion imaging(GMPI).Methods Six healthy male Beagle dogs underwent 13N-NH3 PET GMPI 1 week before irradiation and 3,6 and 12 months after irradiation in the anterior wall of the left ventricle with a single dose of 20 Gy.Global myocardial function parameters including left ventricular ejection fraction (LVEF),end-diastolic volume (EDV),end-systolic volume (ESV),and regional myocardial function parameters including wall motion (WM),wall thickening (WT),end-diastolic perfusion (EDP),end-systolic perfusion (ESP) before and after irradiation were compared by repeated measures analysis of variance and paired t test.Results There were no significant changes between EDV,ESV and LVEF at baseline and those at 3 months after irradiation.EDV at 6 months after irradiation still had no change,compared with baseline value and EDV at 3 months after irradiation,but ESV was increased and LVEF was decreased.Twelve months after irradiation,ESV was further expanded,LVEF was further reduced,and EDV began to increase (F values:20.974-177.846,all P＜0.05).Compared with the baseline,WM,WT,EDP and ESP were increased in 10％(2/20),20％(4/20),10％(2/20) and 15％(3/20) of myocardial segments at 3 months after irradiation (t values:14.446-672.315,all P＜0.05);those parameters were decreased in 15％(3/20),20％(4/20),15％(3/20) and 25％(5/20) of myocardial segments at 6 months after irradiation (t values:18.171-723.156,all P＜0.05),and were decreased in 35％(7/20),45％(9/20),40％(8/20) and 60％ (12/20) of myocardial segments at 12 months after irradiation (t values:14.783-711.259,all P＜0.05).Conclusions 13N-NH3 PET GMPI could be used to detect RIHD early and monitor the dynamic development of RIHD.Compared with the global left ventricular function parameters,regional myocardial function parameters (WM,WT,EDP and ESP) are more sensitive,which may be served as the early monitoring indicators for RIHD.
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Objective To explore the dynamic changes of endothelial barrier antigen (EBA) and vascular endothelial growth factor (VEGF) expressions in cerebral cortex under the condition of blood-brain barrier damage in rats following radi?ation-induced brain injury, which provided clinical references. Methods Forty-eight clean grade male SD rats were divid?ed into the control group and 7 d, 14 d, 28 d after brain irradiation group (n=12 for each group) by using stochastic indicator method. The radiation-induced brain injury model was established by using electronic computer X-ray tomography tech?nique. The 3%Evans blue (EB) was injected into rats according to the dose of 3 mL/kg via the tail vein, then the blood ves?sels of cerebral cortex were exposed after having a craniotomy. EB extravasation was detected by microcirculation micro?scope. The permeability of blood-brain barrier was evaluated by using microscope vascular camera device. The expressions of EBA and VEGF in the cerebral cortex were measured by immunohistochemistry staining in each group. Results Both of EB extravasation and VEGF expression in rat cerebral cortex were significantly increased in injury group at day 7, 14 and 28 after brain irradiation compared with those of control group (P<0.05), and which were gradually decreased from day 7 to day 28 after brain irradiation. There were significant differences in EB extravasation and VEGF expression between the injury subgroups (P<0.05). There was a positive correlation between EB extravasation and VEGF expression (r=0.898, P<0.001). The expression levels of EBA were decreased at different time points in injury groups compared with those of control group (P<0.05), and gradually increased from day 7 to 28 after injury. There were significant differences in expression levels of EBA between injury subgroups (P<0.05). The expression of EBA was negatively correlated with EB extravasation (r=-0.866, P<0.001). Conclusion The increases of blood-brain barrier permeability have important relation to the decreases of EBA expression and the increases of VEGF expression after radiation-induced brain injury.
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Objective To investigate the changes in cathepsin B (CatB) expression in acutely photodamaged human dermal fibroblasts (HDFs) and their significance.Methods HDFs were isolated from the foreskin of children,and subjected to primary culture and subculture.The fourth-to eighth-passage HDFs were used in the following experiment.HDFs were divided into two groups to receive irradiation with different doses of ultraviolet A (UVA) for different durations (acutely photodamaged group) or remain unirradiated (control group).Cell counting kit-8 (CCK8) assay was conducted to evaluate the proliferative activity of HDFs after irradiation with UVA at 5,10,15,20 and 25 J/cm2 respectively.Western blot and quantitative real-time reverse transcription PCR were performed to measure the protein and mRNA expressions of CatB respectively in HDFs at 24,48 and 72 hours after exposure to UVA at 10 J/cm2,and at 48 hours after exposure to UVA at 10,15,20 and 25 J/cm2.Statistical analysis was carried out by analysis of variance and least significant difference (LSD) test using the SPSS 13.0 software.Results UVA radiation induced a decrease in the proliferative activity of HDFs.When the dose of UVA was ≤ 10 J/cm2,the survival rate of HDFs maintained higher than 85％,and significant differences were observed in cell survival rate between unirradiated and irradiated HDFs at 24,48 and 72 hours (all P ＜ 0.05).Western blot showed that the gray value of CatB protein in the acutely photodamaged group irradiated with 10 J/cm2 UVA was significantly higher than that in the control group at 24 hours (0.76 ± 0.14 vs.0.35 ± 0.01,P ＜ 0.05),48 hours (1.34 ± 0.38 vs.0.45 ± 0.12,P＜ 0.05) and 72 hours (0.82 ± 0.09 vs.0.61 ± 0.06,P＜ 0.05).Increased mRNA expressions of CatB were also observed in the acutely photodamaged group compared with the control group at 24 hours (0.149 ± 0.009 vs.0.089 ± 0.015,P ＜ 0.05),48 hous (0.173 ± 0.009 vs.0.091 ± 0.010,P ＜ 0.05) and 72 hours (0.185 ± 0.158 vs.0.111 ± 0.017,P ＜ 0.05) after UVA radiation at 10 J/cm2.The gray value of CatB protein was 0.99 ± 0.07,1.49 ± 0.14,1.89 ± 0.08,2.07 ± 0.06 in HDFs at 48 hours after exposure to UVA of 10,15,20 and 25 J/cm2,respectively,significantly higher than that in the control group (0.60 ± 0.05,all P ＜ 0.05).Similarly,the mRNA expression of CatB was up-regulated in HDFs at 48 hours after UVA radiation at 10,15,20 and 25 J/cm2 compared with the unirradiated HDFs.Conclusion The protein and mRNA expressions of CatB are up-regulated in acutely photodamaged HDFs induced by UVA radiation.
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Objective To discuss the importance of regulatory role of panaxoside Rg1 in Cdk5 in the process of hippocampal neuron radioactive damage protection.Methods Radioactive brain damage in vivo 40 models were built,and divided into 4 groups,including 0 Gy group (short for blank group),pure panaxoside Rg1 preconditioning group (short for control group),30 Gy group (short for model group),and 30Gy + panaxoside Rg1 preconditioning group (short for traditional Chinese medicine group).Hippocampal neurons were separated and trained.Hippocampal neuron apoptosis condition was tested in every group by 4′,6-diamidino2-phenylindole (DAPI) staining method.The p35 and p25 protein expressions were tested with Western blot.Cdk5 was restrained by Cdk5 restrainer roscovitine.Hippocampal neuron damage after Cdk5 blocking-up was observed with changes of X ray in every group.Results Compared with blank group,no significant difference was found in nuclear shrinkage percentage,the number of neuron survival,and the protein expression levels of p35 and p25 in control group ; nuclear shrinkage percentage and the protein expression levels of p35 and p25 were significantly increased and the number of neuron survival was significantly decreased in the model group and traditional Chinese medicine group (P ＜ 0.05).Compared with model group,nuclear shrinkage percentage and the protein expression levels of p35 and p25 were significantly decreased and the number of neuron survival was significantly increased in the traditional Chinese medicine group (P ＜ 0.05).For the addition of dimethyl sulfoxide (DMSO) in every group,the nuclear shrinkage percentage was not significantly changed in control group compared with blank group,was significantly increased in model group and traditional Chinese medicine group compared with blank group (P ＜ 0.05),and was significantly decreased in traditional Chinese medicine group compared with model group (P ＜ 0.05).Conclusions Panaxoside Rg1 can reduce neuron apoptosis by controlling Cdk5,and plays a protective role in hippocampal neuron radioactive damage.
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Objective To evaluate the effect of fractional Er:YAG laser therapy on collagen and elastic fibers in photoaged skin of ultraviolet-irradiated Guinea pigs.Methods Sixty Guinea pigs were randomly divided into the non-intervention group (n =10) and model group (n =50) by a random number table.To establish a model of photoaging,the 50 Guinea pigs were irradiated by ultraviolet A (UVA) and ultraviolet B (UVB) on the back every other day for two months.Subsequently,the 50 mice were equally classified into five groups:photoaging group receiving no laser therapy,as well as 2-week,4-week,8-week and 12-week group receiving one,one,two and three sessions of successive multi-pulsed fractional Er:YAG laser therapy,respectively,on the left side (treatment side) of the back,with the right side as the control side.The interval of laser therapy was four weeks.Skin biopsies were obtained from the right and left side of the back of Guinea pigs after the laser therapy,and subjected to haematoxylin and eosin (HE) staining,Masson staining and Weigert-van Gieson staining.The content of hydroxyproline was measured by using an alkaline-hydrolysis method.Results The minimal erythema dose for UVA and UVB was 4224 mJ/cm2 and 504 mJ/cm2 respectively on Guinea pig skin.The model for photoaging was successfully established in 50 Guinea pigs after two months of irradiation with the cumulative dose of UVA and UVB being 459.36 J/cm2 and 54.81 J/cm2 respectively.HE staining revealed an obvious increase in newly-growing collagen and elastic fibers,which were arranged densely,in the treatment side compared with the control side of the back of Guinea pigs after laser therapy.The area ratio of collagen fibers stained positive for Masson's trichrome and content of hydroxyproline were significantly higher in the treatment side than in the control side of the 12-week group (0.70 ± 0.12 vs.0.63 ± 0.08,t =1.18,P ＜ 0.05;(4.73 ± 0.39) mg/g vs.(3.66 ± 0.85) mg/g,t =3.40,P ＜ 0.05).Conclusion Successive multi-pulsed fractional Er:YAG laser irradiation can result in an increase in collagen fibers and renewal of elastic fibers in superficial dermis of photoaged skin of Guinea pigs.
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Objective To observe the effects of gypenosides (GP) on nuclear factor κB (NF-κB) and p38 mitogen activated protein kinase (p38MAPK) signaling pathways in photodamaged skin of mice,and to explore the mechanisms underlying the protective effects of GP against photodamage.Methods Eighty Balb/C female mice were randomly divided into 8 groups: blank control group receiving no treatment,ultraviolet B (UVB) model group receiving UVB irradiation for 60 seconds,GP group Ⅰ receiving topical GP treatment followed by UVB irradiation,GP group Ⅱ receiving UVB irradiation followed by topical GP treatment,VitE group Ⅰ receiving topical VitE treatment followed by UVB irradiation,VitE group Ⅱ receiving UVB irradiation followed by topical VitE treatment,matrix group Ⅰ receiving topical matrix treatment followed by UVB irradiation,matrix group Ⅱ receiving UVB irradiation followed by topical matrix treatment.UVB irradiation lasted 60 seconds at one time,and was given once every other day for 7 times to establish a skin model of photodamage.The interval between irradiation and topical treatment was 30 minutes in all the groups except the control group and UVB model group.After the last treatment,mice were sacrificed.Western blot was performed to measure the protein expressions of inhibitor of NF-κB(IκB),inhibitor of NF-κB kinase (IKK),p38MAPK as well as phosphorylated p38MAPK (pp38) in skin tissue from the mice.Results No expressions of IκB or IKK were observed in the blank control group.The expression level of IκB was 0.40 ± 0.07 in UVB model group,significantly lower than that in GP group Ⅰ (1.63 ± 0.85,P ＜ 0.05) and GP group Ⅱ (0.90 ± 0.40,P ＜ 0.05),whereas the level of IKK protein was higher in UVB model group than in the GP group Ⅰ and Ⅱ (2.01 ± 1.75vs.0.23 ± 0.12 and 0.45 ± 0.29,both P ＜ 0.05).No significant difference was observed in the expression of IκB or IKK proteins between the GP group Ⅰ,Ⅱ,VitE group Ⅰ and Ⅱ or in the expression of p38MAPK between the 8 groups.The phosphorylated p38MAPK expression in UVB model group was significantly higher than that in GP group Ⅰ and Ⅱ (0.835 ± 0.049 vs.0.425 ± 0.054 and 0.571 ± 0.090,both P＜ 0.05),but similar to that in VitE groups.Conclusions UVB can activate NF-κB and phosphorylated p38MAPK signaling pathways; GP 1.5％ cream can inhibit UVB-induced activation of NF-κB and p38MAPK pathways,which may be one of the mechanisms underlying its protective effects against inflammation and photodamage.
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The extracellular matrix metalloproteinase inducer (EMMPRIN) has been known to play a key regulatory role in pathological angiogenesis. A elevated activation of vascular endothelial growth factor (VEGF) following radiation injury has been shown to mediate blood-brain barrier (BBB) breakdown. However, the roles of EMMPRIN and VEGF in radiation-induced brain injury after gamma knife surgery (GKS) are not clearly understood. In this study, we investigated EMMPRIN changes in a rat model of radiation injury following GKS and examined potential associations between EMMPRIN and VEGF expression. Adult male rats were subjected to cerebral radiation injury by GKS under anesthesia. We found that EMMPRIN and VEGF expression were markedly upregulated in the target area at 8-12 weeks after GKS compared with the control group by western blot, immunohistochemistry, and RT-PCR analysis. Immunofluorescent double staining demonstrated that EMMPRIN signals colocalized with caspase-3 and VEGF-positive cells. Our data also demonstrated that increased EMMPRIN expression was correlated with increased VEGF levels in a temporal manner. This is the first study to show that EMMPRIN and VEGF may play a role in radiation injuries of the central nervous system after GKS.
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Animals , Male , Rats , Basigin/metabolism , Brain/blood supply , Brain Injuries/metabolism , Caspase 3/metabolism , Gamma Rays/adverse effects , Immunohistochemistry , Microscopy, Electron, Transmission , Parietal Lobe/metabolism , Radiation Injuries, Experimental/metabolism , Radiosurgery/adverse effects , Rats, Wistar , Time Factors , Vascular Endothelial Growth Factor A/metabolismABSTRACT
Objective To study the inductive effect of targeted UVB phototherapy on skin hyperpigmentation and its mechanism.Methods Ten brownish guinea pigs were used to develop experimental models.After depilation,four adjacent areas were selected on the back of each guinea pigs and served as the control,low-dose,moderate-dose and high-dose group to receive targeted UVB irradiation with a cumulative dose of O,2500,3500,4500 mJ/cm2,respectively.After 6-week irradiation,the guinea pigs were sacrificed and skin sampies were obtained.The hyperpigmentation induced by UVB irradiation was estimated by naked eyes,staining for melanocytes(Imokawa method)and melanin granules(Masson-Fontana staining),respectively.Immunohistochemistry was carried out to determine the level of nitric oxide synthase and HE staining to observe epidermal histological changes.Results A statistical difference was observed in the pigmentation score,quantity of melanin granules and dopa-positive melanocyte number among the four groups (P<0.05),and the moderatedose group was higher than the high-dose group in terms of these parameters.The expression of inducible nitric oxide synthase increased in a radiation dose-dependent manner,and the median value for inducible nitric oxide synthase expression level was 0.50,1.25,1.75,2.00 in the control,low-dose,moderate-dose and highdose group,respectively(P<0.05).Conclusions Targeted UVB phototherapy can induce hyperpigmentation of the skin in brownish guinea pigs in a dose-dependent manner,but higher dose may not work better.To irradiate with an initial dose close to or slightly higher than the minimum erythema dose may result in a satisfactory effect with reduced cumulative dose and potential risk for cancer.
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Objective To investigate the expression of intestinal epithelial stem cell markers Msil and Hesl in mouse acute radiation enteritis (RE) model. Methods Forty female BALB/c mice were undergone one-time whole abdominal irradiation by 300 cGy/min β-ray. Thirty mice were selected before irradiation (Day 0) and every six mice were euthanized at day 3,5,7 and 14 after irradiation. The small intestinal were detached and the expression of Msil and Hesl were detected in middle part of small intestinal by quantitative RT-PCR, Western blots, and immunohistochemistry. Subsequently,the difference of Msil and Hesl expression was compared. Results The mouse acute RE model was successfully established. At the 5th day after radiation, the results of quantitative RT-PCR indicated that the relative ΔCt value of Msil and Hesl expression were 15. 17 ± 0. 47 and 15. 83 ± 0. 24respectively, the results of Western blot showed that the integrated intensity were 0. 443±0. 055 and 0. 301 + 0. 047 for Msil and Hesl. The expressions were significantly higher than other time points at RNA and protein levels (P<0. 05). The results of immunohistochemistry revealed that Msil and Hesl were highly expressed in intestinal crypts at 5th day and 7th day. Conclusions The expression of Msil and Hesl, upregulated before wound repair in RE model, indicates that intestinal epithelial repair is related to intestinal stem cell proliferation.
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Objective To investigate the expression changes of microRNA 146a (miRNA146a) in UVBdamaged mouse skin. Methods C57/BL6 mice were divided into dose groups to be irradiated on the back with UVB of 30, 60, 90, 180, 270 mJ/cm2 respectively for 24 hours, and time groups irradiated with UVB of 180 mJ/cm2 for 1, 12, 24 and 48 hours respectively. The mice received no irradiation served as the control. Skin samples were subsequently obtained from the irradiated sites of mice and subjected to real-time fluorescent PCR for the detection of miRNA146a expression as well as immunohistochemical staining (IHC) for the detection of STAT3. Results The expression levels of miRNA146a were 0.01158 ± 0.00098, 0.01083 ± 0.00104,0.00872 ± 0.00031, 0.00851 ± 0.00033, 0.00810 ± 0.00057 and 0.00770 ± 0.00031 in the unirradiated control mice and mice irradiated with UVB of 30, 60, 90, 180, 270 mJ/cm2 for 24 hours, respectively, 0.00730 ±0.00036, 0.00805 ± 0.00035, 0.00810 ± 0.00057 and 0.00837 ± 0.00039 in mice irradiated with UVB of 180mJ/cm2 for 1, 12, 24 and 48 hours, respectively. IHC suggested an intensive expression of phosphorylated STAT3 in mice irradiated with a high dose UVB. Conclusions miRNA146a may play an essential role in the mechanism of UVB-induced photodamge, which is mainly correlated with the negative regulation of inflammatory reaction likely mediated by the JAK/STAT3 signal transduction pathway.
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PURPOSE: To evaluate the influence of PRP addition on bone repair of circular defects created in irradiated tibiae of rats by histometric analysis. METHODS: Sixty male Wistar rats had the right tibiae irradiated with 30 Gy. After 30 days monocortical defects were created and platelet-rich plasma was applied in 30 rats. In the control group defects were created but not filled. The animals were desanguinated after 4, 7, 14, 21, 56 and 84 days and the tibiae removed for histological processing. RESULTS: There was a tendency in the PRP group to increased bone neoformation from 14-days to 84-days; in the control group increased bone neoformation was not seen after 21 days or later. CONCLUSION: The addition of platelet-rich plasma had a beneficial effect in the initial cellular regeneration period and enhanced bone formation in later periods when compared to control.
OBJETIVO: Avaliar histometricamente a influência do PRP na reparação óssea de defeitos circulares criados em tíbia irradiada de ratos Wistar. MÉTODOS: Sessenta ratos machos tiveram a tíbia direita irradiada com 30Gy. Após 30 dias, defeitos ósseos monocorticais foram criados e PRP foi adicionado em 30 ratos. No grupo controle os defeitos foram criados, mas não preenchidos. Os animais foram sacrificados em 4, 7, 14, 21, 56 e 84 dias e a tíbia removida para processamento histológico. RESULTADOS: Houve uma tendência do grupo PRP mostrar uma neoformação óssea significativamente maior nos períodos de 14 a 84 dias; no grupo controle o aumento da reparação óssea não se manteve após 21 dias. CONCLUSÃO: A adição de PRP mostrou-se benéfica no período inicial de reparação celular e em períodos seqüentes foi estímulo à quantidade neoformação óssea, quando comparado ao controle.
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Animals , Male , Rats , Bone Regeneration/physiology , Intercellular Signaling Peptides and Proteins/physiology , Platelet-Rich Plasma , Tibia/radiation effects , Bone Regeneration/radiation effects , Platelet Count , Radiation Injuries, Experimental , Rats, Wistar , Time FactorsABSTRACT
Objective To study the relationship between ATP level changes detected by hepatic 31P MRS with the pathologic changes of liver in rabbits and to investigate the diagnostic value of ATP level changes in acute hepatic radiation injury. Methods A total of 30 rabbits received different radiation doses ( ranging from 5,10,20 Gy) to establish acute hepatic injury models. Blood hepatic function tests, 31P MRS and pathological examinations were carried out 24 h after irradiation The degree of injury was evaluated according to hepatocyte pathology. Ten healthy rabbits served as controls. The MR examination was performed on a 1.5 T imager using a 1H-31P surface coil with 2D chemical shift imaging technique. The relative quantities of phosphomonoesters (PME), phosphodiesters (PDE), inorganic phosphate (Pi) and adenosine triphosphate (ATP) were measured. Analysis of variance was used to compare the results of 31P MRS and histopathology under various acute hepatic radiation injuries, and SNK was used further to conduct comparison between each other if there was significant difference. Results The ATP relative quantification in control( n= 10), mild ( n = 12), moderate ( n = 11 ), and severe ( n = 7 ) injury groups according to pathological grading were 1.83 ± 0. 33, 1.58 ± 0. 25, 1.32 ± 0. 07 and 1.02 ± 0. 18, with significant differences among them (F =22. 878 ,P ＜0. 01 ), and it decreased progressively with the increased degree of injury. The PDE index showed no significant trend for the evaluation of hepatic radiation injury. The area under the peak of β-ATP decreased with the increased severity of radiation injury. Conclusions The relative quantification of hepatic ATP levels can reflect the pathological severity of acute hepatic radiation injury. The decreasing hepatic ATP levels may be used as biomarker of acute liver injury following radiation.
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Objective To study the effect of 125Iodine seed on the rabbit ischiadic nerve at different time point after implantation. Methods Thirty healthy New-Zealand rabbits were randomly assigned into 3 groups( 2-week group, 2-month group and 4-month group) using envelope method. During operation, 10 radioactive 125I seeds were implanted randomly near one of the ischiadic nerve, while 10 non-radioactive seeds were implanted into the contralateral ischiadie nerve. According to treatment plan system(TPS),90% of the prescription dose (PD)was centered in the specific place, where the nerves were chosen to be studied. After 2 weeks, 2 months and 4 months respectively, nerve electro-physiolngy experiment was used to evaluate the bilateral ischiadic nerves, at the same time the morphology of the ischiadic nerve was examined by general observation, light microscope and electron microscope. The electron microscope photo with the same ×4000 amplification was divided into 100( 10 × 10) cages and non-specific changes in one cage account for 1%. The t test and sum rank test were used for statistics. Results Potential leaking point of experimental ischiadic nerves near heart in 2-week group ,2-month group and 4-month group were (0.52± 0.26), (0.60±0.19), (0.48±0.17)V, while that of the control sides were (0.59±0.19), (0.60± 0.15), (0.53±0.13 ) V, there was no statistical significance in the same group respectively (t=0.91, 0.03,0.67,P>0.05). Potential leak point of experimental ischiadic nerves far from heart in 2-week group, 2-month group and 4-month group were (0.51±0.15), (0.52 s0. 11 ), (0. 53±0.15) V,the control sides were (0.52±0.10), (0.56±0.12), (0.54±0.10)V, there was no statistical significance in the same group respectively (t= 0.25,0.74,0.17, P > 0.05 ). Action potential amplitude of experimental ischiadic nerves near heart in 2-week group,2-menth group and 4-month group were (13.18±4.09), (12.78± 4.42), (12.09±1.20) mV, while that of the control sides were (10.55± 4.21 ), ( 10.31±4.22), (12.88±3.54) mV, there was no statistical significance in the same group respectively (t=1.57,1.36, 0.50,P>0.05). Action potential amplitude of experimental ischiadic nerves far from heart in 2-week group,2-month group and 4-month group were (11.18±3.38), (11.68±3.21), ( 12.52±3.09) mV, while that of the control sides were (11.56±4.80), (10.71±3.40), (11.67±2.48) mV ,there was no statistical significance in the same group respectively(t=0.29,1.01,0.55, P>0.05 ). Nerve conduction velocity of experimental ischiadic nerves in 2-week group,2-month group and 4-month group were (40.56± 9.46), (38.79±5.78), (39.44±8.64) m/V, the control sides were (42.56±6.59), (44.64±7.53), (43.33±6.05)m/V, there was no statistical significance in the same group respectively( t = 0.57,1.94, 0.01,P>0.05). There were some changes in general observation and light microscope, in electron microscope, many non-specificity changes were observed. All of these changes included delamination, collapse, disaggregation of the myelinated nerve, mitochondria swelling and vacuolization of neurilemma cell and axon. The ratio of degenerative alterations in nerves was 60% --70% in 2-week group, 50% in 2-month group and 30% in 4-month group, and there was statistical significance among three groups (P<0.05). Conclusion 125I permanent plantation in our test dose has little effect on ischiadic nerve, all these non-specificity changes were observed in electron microscope, and it has no evident impacts on physiological functions.
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Objective To study the correlation between high resolution computed tomography manifestations and expression of transforming growth factor beta,tumor necrosis factor alpha in radiationinduced lung injury of rats,and to investigate the vslues of cytokine detection and HRCT scanning for the prediction and early diagnosis of radiation-induced lung injury.Methods Forty-eight Sprague-Dawley (SD)rats were randomly divided into eight groups,group A was normal control group.and group BH were irradiated with a single dose of 15 Gy to the lungs.HRCT scanning Wag performed before and 1 week,2,4,8,12,16,24 weeks after radiation in group A-H respectively.The expression of TGF-beta and TNF-alpha were detected with ELISA. All the rats were killed to observe pathological changes of their lungs.HRCT signs,levels of cytokine were simultaneously compared and analyzed.The t-test and Spenrman rank correlation were used for the statistics.Results Four HRCT signs were observed during the 24 weeks after radiation,including ground-glass opacity(1 case),patchy consolidation(8 cases),massive consolidation(7 cases)and fibrosis(3 cases).The average levels of TGF-beta in group B-H[(3.33±0.47),(3.20±0.65),(3.12±0.45),(3.54±0.80),(3.30±1.13),(2.49±0.67),(4.19±0.22)μg/L,respectively]were hisher than the control group[(0.45±0.14)μg/L.P＜0.05].At 24 weeks the average level increased to the highest peak[(4.19 4-0.22)μg/L,P＜0.05].At 1 week and 2,4,8,12 weeks after radiation,the average level of TNF-alpha in radiation group[(236.52±29.01),(214.91±34.53),(270.97±42.12),(208.83±86.51),(208.83±82.23)ng/L]was hisher than the control group[(31.78±0.92)ng/L,P＜0.05].The average level increased to the highest peak [(270.97±42.12)ng/L,P＜0.05]at 4 weeks.The average level at 16 and 24 weeks[(60.63±38.49),(32.07±1.05)ng/L]dropped to the level similar to the control group(P＞0.05).There were no rank correlations between HRCT manifestations and expression of TGF-beta and TNF-alpha(rs=0.5570 and 0.1013.P＞0.05).HRCT signs were correlated with pathological changes.Conciusions The monitoring of TGF-beta and TNF.alpha in the serum after irradiation can predict the development of radiation-induced lung injury.There are no rank correlations between HRCT manifestations and expression of TGF-beta and TNF-alpha.
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Objective To study the expression of tumor necrosis factor alpha (TNF-α) in the intestine of mice irradiated by neutron and γ rays.Methods 350 male BALB/c mice were irradiated with neutron and γ rays of different doses, and sacrificed at 6 and 12hours, 1, 2, 3, 4, 5, 7, 10, 14, 21 and 28 days after irradiation.The TNF-α in the mice intestinal tissue was detected by means of immunohistochemistry and image analysis.Results In normal control mice, TNF-α was expressed in the cytoplasm of macrophages in intestinal villus interstitium, submucosa and lymph tissue.After 2.5Gy neutron radiation, TNF-α was decreased progressively within 2 days, increased obviously in macrophages and crypt cells during 3rd～7th day, reached the peak at 5th day and recovered to normal level at 14th day and TNF-α was decreased progressively within 4 days after 4.0 and 5.5Gy neutron and 12Gy ray irradiation.TNF-α was increased obviously in 6～12 hours, decreased at 1st day, increased at 2nd～5th day, peaked at 3rd day and recovered at 10th day after 5.5Gy ray irradiation.Conclusion Neutron and ray radiation induce different expression profile of endogenous TNF-α in small intestine, which may be related with the pathologic courses of irradiation-induced damage and repair of intestine.
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Objective: To investigate the effect of angiotensin-converting enzyme inhibitors (ACEI), captopril (Cap), on the serum levels of transforming growth factor β1 (TGF-β1) and tumor necrosis factor α (TNF-α) in mice after lung irradiation injury. Methods: Male C57/BL mice were divided into three groups: control group, right lung single irradiation group (10 Gy), and right lung single irradiation (10 Gy) plus Cap administration group. The blood samples were collected at 36 h, 7 d, 15 d, and 30 d after irradiation. The levels of TGF-β1 and TNF-α were evaluated with ELISA method. The right lungs were isolated and stained with HE for pathological examination at the same time points. Results: The average serum levels of TGF-β1 and TNF-α in single 10-Gy irradiation group were significantly increased at different time points compared with the control group. But they were significantly decreased at different time points in 10-Gy radiation plus Cap group compared with the control group. The results of analysis of variance showed that there was a significant difference among the factor of time, the factor of treatment, and the factor of interaction (P < 0.05). Pathological examination showed that acute inflammation was aggravated in single 10-Gy irradiation group. But there was no significant difference in lung injury score between 10-Gy irradiation plus Cap group and control group. Conclusions: Cap reduces the serum levels of TGF-β1 and TNF-α and prevents lung against radiation-induced injury.
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The expression of vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF)2 in the irradiated brain was examined to test how a single high dose radiation, similar to that used for intraoperative radiation therapy given to the normal cerebrum, can affect the vascular endothelium. After a burr hole trephination in the rat skull, the cerebral hemisphere was exposed to a single 10 Gy dose of gamma rays, and the radiation effect was assessed at 1, 2, 4, 6, and 8 weeks after irradiation. His-tological changes, such as reactive gliosis, inflammation, vascular proliferation and necrosis, were correlated with the duration after irradiation. Significant VEGF and FGF2 expression in the 2- and 8-week were detected by enzyme-linked immunosorbent assay quantification in the radiation group. Immunohistochemical study for VEGF was done and the number of positive cells gradually increased over time, compared with the sham operation group. In conclusion, the radiation injuries consisted of radiation necrosis associated with the expression of VEGF and FGF2. These findings indicate that VEGF and FGF2 may play a role in the radiation injuries after intraoperative single high-dose irradiation.
Subject(s)
Animals , Rats , Brain/metabolism , Brain Injuries/etiology , Fibroblast Growth Factor 2/metabolism , Necrosis , Radiation Injuries/pathology , Radiosurgery/adverse effects , Rats, Sprague-Dawley , Up-Regulation/radiation effects , Vascular Endothelial Growth Factor A/metabolismABSTRACT
Objective To study comparatively the changes in epi th elial growth factor (EGF) and its receptor (EGFR) in injured intestine induced b y neutron and ?-ray irradiation in mice and their significance. Method s 350 male BALB/C mice were irradiated with neutron and ?-rays, and t hey were sacrificed at 6 and 12 hours and 1, 2, 3, 4, 5, 7, 10, 14, 21 and 28 da ys, respectively, after irradiation. Immunohistochemical method was employed to assess EGF and EGFR in the intestinal tissue of the mice. Results After the neutron radiation with 2.5Gy dosage, the expressions of EGF and E GFR in the cytoplasm of mucosa epithelial cells and crypt cells were obviously u p-regulated within 1 day, decreased after 1~2 days, increased again on 3~7 days , reached the peak value at the 5th day, and returned to normal values in 14 day s. Whereas EGF and EGFR were increased at 6 hours and progressively decreased fr om 12 hours up to 4 days after 4.0 and 5.5Gy neutron and 12Gy g-ray radiation . They were increased progressively within 3 days, reaching peak value on the 3r d day, and returned to normal values 5 days after 5.5Gy g-ray irradiation. Conclusions The expressions of endogenous EGF and EGFR showed diffe rent regularities after neutron and g-ray radiation, and they were involved in the pathologic courses of radiation damage and recovery of the intestine.