Proteomic analysis of acute radiation-induced rectal injury in rats

Objective:To comprehensively elucidate overall protein alterations associated with acute radiation-induced rectal injury in rats.Methods:A rat model of acute radiation-induced rectal injury was established by irradiating rectal segments with a single dose of 17.5 Gy X-rays.These segments were then collected at 7 d and 10 d post-irradiation.Tandem mass tag-based quantitative proteomic analysis was then performed.Results:65,526 peptides were identified,corresponding to 8,088 proteins.Hematoxylin-eosin staining revealed characteristic epithelial cell degeneration and necrosis,intestinal gland atrophy and dilatation,and interstitial inflammatory cell infiltration.Inflammation was more pronounced in the 10 d irradiation group than in the 7 d irradiation group.Overall,127 up-and 108 downregulated proteins were identified at 7 d post-irradiation,and 122 up-and 44 downregulated proteins were identified at 10 d post-irradiation.Notably,17 up-and 6 downregulated proteins were consistently co-expressed at both time points.The expression of three of these proteins was validated via real-time quantitative PCR:polypeptide YY(Pyy),thymidylate synthase(Tyms),and tetraspanin(CD9).Tyms transcript levels were significantly higher in irradiated rectal tissues(P<0.05).Pyy transcript levels were significantly higher at both time points(P<0.05).Finally,CD9 mRNA expression was significantly lower in both the 7 d and 10 d irradiation groups(P<0.05).Conclusions:The potential targets were found to prevent and treat acute radiation-induced rectal injury in clinical practice.

Treatment of radiation-induced brain injury with bisdemethoxycurcumin

Radiation therapy is considered the most effective non-surgical treatment for brain tumors.However,there are no available treatments for radiation-induced brain injury.Bisdemethoxycurcumin(BDMC)is a demethoxy derivative of curcumin that has anti-proliferative,anti-inflammatory,and anti-oxidant properties.To determine whether BDMC has the potential to treat radiation-induced brain injury,in this study,we established a rat model of radiation-induced brain injury by administe ring a single 30-Gy vertical dose of irradiation to the whole brain,followed by intraperitoneal injection of 500μL of a 100 mg/kg BDMC solution every day for 5 successive weeks.Our res ults showed that BDMC increased the body weight of rats with radiation-induced brain injury,improved lea rning and memory,attenuated brain edema,inhibited astrocyte activation,and reduced oxidative stress.These findings suggest that BDMC protects against radiationinduced brain injury.

TLD calibration and absorbed dose measurement in a radiation-induced liver injury model under a linear accelerator

The application of a thermoluminescent detector(TLD) for dose detection at the liver irradiation site in mice under linear accelerator precision radiotherapy and the use of a single high dose to irradiate the mouse liver to construct a biological model of a radiation-induced liver injury(RILD) in mice were to determine the feasibility of constructing a precision radiotherapy model in small animals under a linear accelerator. A 360° arc volumetric rotational intensity-modulated radiotherapy(VMAT) plan with a prescribed dose of 2 Gy was developed for the planned target volume(PTV) at the location of the TLD within solid water to compare the difference between the measured dose of TLD and the assessed parameters in the TPS system. The TLD was implanted in the livers of mice, and VMAT was planned based on TLD to compare the measured and prescribed doses. C57BL/6 J mice were randomly divided into control and 25-Gy radiation groups and were examined daily for changes in body weight. They were euthanized at 3 and 10 weeks after radiation, and the levels of liver serum enzymes such as alanine aminotransferase(ALT), aspartate aminotransferase(AST), and alkaline phosphatase(ALP) were measured to observe any pathological histological changes in the irradiated areas of the mouse liver. The measured values of solid underwater TLD were within ± 3% of the Dmean value of the evaluation parameter in the TPS system. The mice in the 25-Gy radiation group demonstrated pathological signs of radiation-induced liver injury at the site of liver irradiation. The deviation in the measured and prescribed doses of TLD in the mouse liver ranged from-1.5 to 6%;construction of an accurate model of RILD using the VMAT technique under a linear accelerator is feasible.

Rabbit model of radiation-induced lung injury

Objective:To explore the feasibility of establishing an animal model of chronic radiationinduced lung injury.Methods:Twenty-eight New Zealand white rabbits were randomly divided into 3 groups(the right lung irradiation group,the whole lung irradiation group and the control group).Animal model of radiation-induced lung injury was established b) highdoes radiotherapy in the irradiation groups,then all rabbits underwent CT and pathological examinations at 1.2.4.8.12.16 weeks,respectively after radiation.Results:Within 4 weeks of irradiation,some rabbits in the right lung irradiation group and whole lung irradiation group died. CT and pathological examinations all showed acute radiation pneumonitis.At 8-12 weeks after irradiation,CT scanning showed ground glass samples signs,patchy shadows and fibrotic stripes. Pathological examination showed the fibrosis pulmonary alveolar wall thickened obviously. Conclusions:The clinical animal model of chronic radiation-induced lung injury which corresponds to practical conditions in clinic can be successfully established.

Correlation between miR-564, TGF-β1, and radiation-induced lung injury

Objective Our study aimed to analyze the expression of miR-564 and TGF-β1 in cancer tissues and the serum of patients with radiation-induced lung injury,and to investigate the relationship between them and radiation-induced lung injury.Methods In situ hybridization and real-time fluorescence quantitative method were used to detect the expression of miR-564.Additionally,immunohistochemistry and enzyme-linked immunosorbent assay(ELISA)were performed to detect the expression of TGF-β1.Results The overall incidence of acute radiation pneumonia was 55.9%(100/179).The incidence of≥grade 2 radioactive pneumonia was 24.0%(43/179)and that of grade 1 was 31.8%(57/179).The expression of miR-564 in grade≥2 was slightly higher than that in patients without or with grade 1,but there was no statistical difference(P=0.86).The serum level and ratio of miR-564 in patients with grade≥2 were significantly higher than those without or with grade 1(P=0.005,P=0.025,respectively).The expression of TGF-β1 in grade≥2 was significantly higher than that of patients without or with grade 1(P=0.017).The serum levels of TGF-β1 in grade≥2 were significantly higher than those in patients without or with grade 1(P=0.038).Although the ratio of TGF-β1 in radiation pneumonia of grade≥2 was significantly higher than that of without or with grade 1,there was no significant difference(P=0.24).Moreover,patients with higher expression of miR-564 and lower expression of TGF-β1 had better prognosis.Conclusion MiR-564 and TGF-β1 are predictors of radiation-induced lung injury.Monitoring its changing trend can improve the accuracy of predicting radiation-induced lung injury.The levels and ratio of serum miR-564 and TGF-β1 in patients with radiation-induced lung injury are related to the severity of radiationinduced lung injury.

Neuron-specific enolase expression in a rat model of radiation-induced brain injury following vascular endothelial growth factor-modified neural stem cell transplantation

BACKGROUND： Previous studies have shown that transplantation of vascular endothelial growth factor （VEGF）-modified neural stem cells （NSC） provides better outcomes, compared with neural stem cells, in the treatment of brain damage. OBJECTIVE： To compare the effects of VEGF-modified NSC transplantation and NSC transplantation on radiation-induced brain injury, and to determine neuron-specific enolase （NSE） expression in the brain. DESIGN, TIME, AND SETTING： The randomized, controlled study was performed at the Linbaixin Experimental Center, Second Affiliated Hospital, Sun Yat-sen University, China from November 2007 to October 2008. MATERIALS： VEGF-modified C17.2 NSCs were supplied by Harvard Medical School, USA. Streptavidin-biotin-peroxidase-complex kit （Boster, China） and 5, 6-carboxyfluorescein diacetate succinimidyl ester （Fluka, USA） were used in this study. METHODS： A total of 84 Sprague Dawley rats were randomly assigned to a blank control group （n = 20）, model group （n = 20）, NSC group （n = 20）, and a VEGF-modified NSC group （n = 24）. Rat models of radiation-induced brain injury were established in the model, NSC, and VEGF-modified NSC groups. At 1 week following model induction, 10 pL （5 ×10^4 cells/μL） VEGF-modified NSCs or NSCs were respectively infused into the striatum and cerebral cortex of rats from the VEGF-modified NSC and NSC groups. A total of 10μL saline was injected into rats from the blank control and model groups. MAIN OUTCOME MEASURES： NSE expression in the brain was detected by immunohistochemistry following VEGF-modified NSC transplantation. RESULTS： NSE expression was significantly decreased in the brains of radiation-induced brain injury rats （P 〈 0.05）. The number of NSE-positive neurons significantly increased in the NSC and VEGF-modified NSC groups, compared with the model group （P 〈 0.05）. NSE expression significantly increased in the VEGF-modified NSC group, compared with the NSC group, at 6 weeks following transplantation （P 〈 0.05）. CONCLUSION： VEGF-modified NSC transplantation increased NSE expression in rats with radiation-induced brain injury, and the outcomes were superior to NSC transplantation.

Radiation-induced brain injury after a conventional dose of intensity-modulated radiotherapy for nasopharyngeal carcinoma:a case report and literature review

A 61-year-old female nasopharyngeal carcinoma patient was admitted to the hospital with sudden cognitive dysfunction one month after Volumetric Intensity Modulated Arc Therapy(VMAT)conventional dose radiotherapy,and the initial diagnosis was radiation-induced brain injury(RBI).After comprehensive treatment with steroid hormones,the patient’s condition rapidly improved.Typically,in nasopharyngeal carcinoma patients treated with VMAT,the incidence of RBI is extremely low when the temporal lobe dose is less than 65 Gy or 1%of the volume is less than 65 Gy.When this limit is exceeded,RBI may occur in varying degrees.However,in this case,even though the temporal lobe dose was under the prescribed limit,the patient still experienced RBI.The rare observations in this case can be used as a reference,and clinicians should seriously consider the possibility of RBI in similar cases.

Treatment of benign rectal stricture caused by repeated anal insertion by endoscopy and balloon dilation:A case report

BACKGROUND Benign rectal strictures can be categorized as primary(disease-related)and secondary(surgical anastomosis-related).Secondary strictures arise from surgical complications,whereas primary strictures have diverse etiologies,including various inflammatory conditions.Benign strictures are usually managed by surgery and endoscopy.We present an unusual etiology of benign rectal stricture caused by the repeated insertion of foreign objects into the rectum for sexual purposes,resulting in rectal injury and subsequent chronic inflammation.CASE SUMMARY A 53-year-old man presented to the outpatient clinic of the Colorectal Surgery Department with symptoms of chronic constipation and bloody stools.The patient previously experienced rectal injury due to foreign object insertion for sexual purposes.Colonoscopy revealed benign circumferential narrowing of the rectum.He underwent treatment by endoscopic argon plasma coagulation and balloon dilation and follow-up as an outpatient for 4 months.A colonoscopy at the end of the follow-up period revealed no evidence of rectal stricture relapse.CONCLUSION A history of rectal injury,followed by chronic inflammation,should be considered in patients with benign rectal strictures.Management with endoscopic argon plasma coagulation and balloon dilation can prevent the need for surgical resection of benign rectal strictures.

Time-dependent Changes in CT of Radiation-induced Liver Injury:A Preliminary Study in Gastric Cancer Patients

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.

Prevention and treatment of radiation-induced lung injury by hydroxypiperquin phosphate: a clinical and experimental study

Objective: To evaluate the hydroxypiperquin phosphate (HPQP) as a modifier of radiation-induced injury in human and rat lungs. Methods: Sixty-five patients with lung cancer treated with conventional radiotherapy were divided into 2 groups randomly: Thirty cases were treated with HPQP and the others were in a control group. The changes of X - ray manifestation before, after and during taking drug were compared. An animal model of radiation-induced fibrosis of lungs was also established. Hydroxyproling (HP) content in lung tissue and the pathological changes in rat lungs were checked with microscope and electron microscope after 4 months and 6 months respectively. Results: The changes of lung X-ray manifestation in treatment group were much lighter than that in control group. The HP content and the change of pathology in the lungs of those rats with HPQP treatment were obviously less than that in control group. Conclusion: HPQP plays an important role in prevention and treatment of radiation-induced injury in lungs.

针灸结合三氧直肠灌注对不完全性脊髓损伤小便障碍的疗效研究

目的:观察针灸结合三氧直肠灌注对不完全性脊髓损伤小便障碍患者逼尿肌损伤修复及膀胱功能、应激状态和尿动力学的影响。方法:选择2022年7月—2023年7月于广西壮族自治区江滨医院治疗的86例不完全性脊髓损伤小便障碍患者,按照随机数字表法分为两组,三氧直肠灌注组43例,基础治疗的同时给予患者三氧直肠灌注治疗;针灸联合组43例,三氧直肠灌注组治疗基础上给予患者针灸治疗。比较两组临床疗效,治疗前、后评价中医证候,记录两组患者每次排尿量、膀胱安全容量,给予患者国际下尿路功能症状(LUTS)、尿失禁生活质量问卷(I-QOL)评价,测定膀胱顺应性、充盈期膀胱压力、最大尿流速时逼尿肌压力,检测热休克蛋白70(HSP70)、活性氧(ROS)、超氧化物歧化酶(SOD)水平。结果:针灸联合组总有效率较三氧直肠灌注组高(P<0.05);中医证候评分较三氧直肠灌注组降低(P<0.01);膀胱安全容量、每次排尿量大于三氧直肠灌注组(P<0.01),I-QOL评分高于三氧直肠灌注组(P<0.01),LUTS评分少于三氧直肠灌注组(P<0.01);最大尿流速时逼尿肌压力、充盈期膀胱压力低于三氧直肠灌注组(P<0.05),膀胱顺应性高于三氧直肠灌注组(P<0.01);HSP70、ROS水平低于三氧直肠灌注组(P<0.05),SOD水平高于三氧直肠灌注组(P<0.01)。结论:针灸结合三氧直肠灌注治疗不完全性脊髓损伤小便障碍患者,可抑制氧化应激,促进修复受损逼尿肌,改善尿动力学,提升膀胱功能、排尿功能、临床疗效及生活质量。

子宫内膜癌相关放射性直肠损伤的多因素分析与风险预测模型构建

目的分析子宫内膜癌放疗致放射性直肠损伤(RRI)的影响因素,并进行风险预测模型构建及验证。方法选取2020年2月—2023年2月于南通大学附属肿瘤医院收治的子宫内膜癌行盆腔放疗的老年患者86例,根据RTOG/EORTC分级,将0~1级患者划归为<2级RRI组(n=36),而2~4级患者划归为≥2级RRI组(n=50)。采用单因素、Logistic多因素回归分析法对≥2级RRI发生的高危因素进行分析。结果Logistic回归分析显示,年龄>75岁、肿瘤直径≥4 cm、临床分期Ⅲ~Ⅳ期、HAD评分高(11~21分)、SSRS评分低(分值<20分)、直肠平均受照剂量(mean)≥40 Gy、浸润程度≥1/2及放疗时间≥4周均为导致子宫内膜癌放疗患者发生≥2级RRI的独立危险因素(P<0.05)。构建子宫内膜癌放疗后≥2级RRI的风险预测模型,其Hosmer-Lemeshow检验(χ^(2)=5.138,P>0.05),预测模型的AUC为0.912,95%CI为0.856~0.962,表明子宫内膜癌放疗致≥2级RRI的预测模型有较好的拟合度和预测效能(P<0.05)。结论子宫内膜癌放疗易发生≥2级RRI,这可能与患者的年龄、肿瘤直径、临床分期、HAD评分、SSRS评分、直肠mean≥40 Gy、浸润程度及放疗时间等因素相关,根据各危险因素构建模型可以较好地预测子宫内膜癌放疗后≥2级RRI概率。

经会阴穿刺注射玻璃酸钠扩张狄氏间隙改良前列腺根治性切除术安全性的动物实验

目的通过动物实验组织学观察,探讨经直肠超声引导下经会阴穿刺注射玻璃酸钠扩张狄氏间隙在提升腹腔镜下前列腺根治性切除术安全性方面的价值。方法选用健康雄性纯种比格犬14只,随机分为两组,每组7只。对照组采用常规腹腔镜行根治性前列腺切除,实验组经直肠超声引导下穿刺狄氏间隙注射玻璃酸钠2.5 mL后行腹腔镜根治性前列腺切除。观察两组比格犬总手术时间、分离前列腺时间、术中出血量、直肠状态。结果经前列腺与直肠之间的狄氏间隙注射玻璃酸钠操作后,切下的前列腺中未见直肠组织,且两组后方直肠未见明显损伤。术后对照组血红蛋白(HGB)为(118.70±2.56)g/L低于实验组的(122.10±2.19)g/L(P=0.02);对照组总手术时间为(141.40±9.80)min长于实验组的(119.10±9.16)min(P<0.05);对照组分离前列腺时间为(24.99±1.75)min长于实验组的(16.64±2.34)min(P<0.05);实验组术中出血量为(34.86±5.18)mL明显低于对照组的(47.43±4.32)mL(P<0.05)。结论在动物实验中,经直肠超声引导下穿刺狄氏间隙注射玻璃酸钠2.5 mL后行腹腔镜根治性前列腺切除可缩短总手术时间、分离前列腺时间,减少出血量,可能降低了直肠损伤这一严重并发症的发生率。本研究初步确立了这一方法用于临床前列腺癌根治术的可行性。

Evaluating a novel protective agent against radiation-induced acute intestinal injury

Objective:To develop and synthesize a novel derivative of ethyl pyruvate,named TZC02,and investigate its radioprotective effects against ionizing radiation(IR)-induced intestinal injury in mice.Methods:Male C57BL/6J mice weighing(20±2)g in the survival experiment were randomly divided into five groups(n=10 in each):control group,IR group,IR+TZC02(50 mg/kg)group,IR+TZC02(100 mg/kg)group,and IR+TZC02(200 mg/kg)group.Mice's survival rates were monitored for 7 d.In other experiments,the male mice were randomly divided into three groups(n=5 per group):control group,IR group,and IR+TZC02(100 mg/kg)group.TZC02 was intragastrically administered 1 h before 12 Gy abdominalγ-ray irradiation(ABI)and 24 h,48 h after irradiation,respectively.Three days after IR exposure,small intestinal tissues were collected and the number of small intestinal crypts was determined using hematoxylin&eosin(H&E)staining.Immunohistochemical analysis was used to assess the regenerative capacity of the small intestine(SI)and radiation-induced damage,stemness markers or DNA repair surrogates,including Ki67,lysozyme,and villus.The expressions of histone H2AX phosphorylation(γH2AX)and caspase-3 were evaluated through immunofluorescence analyses.Additionally,in vitro cultured small intestinal organoids were employed to investigate the effects of TZC02 on SI regeneration after irradiation.Results:The administration of TZC02 significantly improved the 7 d-survival rate of mice exposed to 12 Gy ABI(P<0.05).Compared to the IR group,TZC02 treatment attenuated the decrease of SI Ki67-positive cells[(59.60±6.33)vs.(37.70±7.82),t=11.89,P<0.0001]and Paneth cells[(9.90±1.37)vs.(5.50±1.71),t=6.02,P<0.001]in five crypts,and reduced structural damage to the SI[villus height,(349.49±60.17)μm vs.(294.72±40.09)μm;t=3.39;P<0.05].TZC02 also significantly decreased the crypt apoptosis detected by caspase-3[(10.75±1.26)vs.(29.83±2.56),t=13.39,P<0.0001]and DNA damage detected by gH2AX[(10.40±1.14)vs.(29.60±2.70),t=10.13,P<0.0001].The organoid survival 7 d post-irradiation further confirmed the protective effects of TZC02(area of organoids,(0.119±0.081)mm^(2)vs.(0.080±0.037)mm^(2);t=2.30;P<0.05).Conclusions:This study demonstrate that TZC02 can offer effective protection against IR-induced intestinal injury,suggesting its potential as a promising protective compound for patients treated with radiotherapy.

A rare rhabdomyolysis appears after transrectal ultrasound guided prostate biopsy

Dear Editor,Rhabdomyolysis(RM)is a pathophysiological process in which creatine kinase and myoglobin from skeletal muscle cells are released into circulation,leading to lethal acute kidney injury(AKI),hypovolemic shock,electrolyte disturbances and disseminated intravascular coagulation.Although injuries were the first reported and best-known reason for RM,infection currently contributes to approximately 5%of RM[1,2].

Liver injury after aluminum potassium sulfate and tannic acid treatment of hemorrhoids

We are reporting a rare case of acute liver injury that developed after an internal hemorrhoid treatment with the aluminum potassium sulfate and tannic acid(ALTA) regimen. A 41-year-old man developed a fever and liver injury after undergoing internal hemorrhoid treatment with a submucosal injection of ALTA with lidocaine. The acute liver injury was classified clinically as hepatocellular and pathologically as cholestastic. We could not classify the mechanism of injury. High eosinophil and immunoglobulin E levels characterized the injury,and a drug lymphocyte stimulation test was negative on postoperative day 25. Fluid replacement for two weeks after hospitalization improved the liver injury. ALTA therapy involves injecting chemicals into the submucosa,from the rectum to the anus,and this is the first description of a case that developed a severe liver disorder after this treatment; hence,an analysis of future cases as they accumulate is desirable.

精细化护理联合中药保留灌肠在宫颈癌放疗病人放射性直肠损伤中的应用研究

目的:探讨精细化护理联合中药保留灌肠在防治宫颈癌放疗病人放射性直肠损伤中的应用效果。方法:选取2021年10月—2022年12月在我院放疗中发生放射性直肠损伤的60例宫颈癌病人为研究对象,采用随机数字表法将其随机分为对照组和观察组,每组30例。对照组采用常规护理,观察组实施精细化护理联合中药保留灌肠。比较两组治疗效果、放射性直肠损伤严重程度及护理满意度。结果:观察组治疗效果和护理满意度均高于对照组(P<0.05),观察组放射性直肠损伤程度较对照组低,放疗第5周病人发生Ⅱ级放射性直肠损伤例数低于对照组,差异有统计学意义(P<0.05)。结论:精细化护理联合中药灌肠可改善病人放射性直肠损伤症状、提高治疗效果、提升护理满意度。

盆腔放疗发生放射性直肠损伤的关联因素分析

背景盆腹腔放疗是目前恶性肿瘤治疗中不可缺少的方法之一,放疗引起的放射性肠损伤是临床常见的并发症。目的探究妇科肿瘤患者放疗后发生放射性直肠损伤的影响因素。方法回顾分析2012年1月-2022年1月因妇科肿瘤在解放军总医院第一医学中心接受放射治疗的324例患者发生放射性直肠损伤的情况,并对放射性直肠损伤的相关因素进行分析。结果324例患者平均年龄(51.7±10.0)岁,233例(71.9%)发生放射性直肠损伤,其中急性放射性直肠损伤142例(60.9%),慢性放射性直肠损伤91例(39.1%)。放疗总剂量高(OR=1.038,95%CI:1.015~1.062,P<0.001)的患者放射性直肠损伤发生概率高;血压偏高(OR=0.384,95%CI:0.163~0.906,P=0.029)、放疗前化疗(OR=0.433,95%CI:0.237~0.790,P=0.006)的患者放射性直肠损伤发生概率低。放疗总剂量高(OR=1.041,95%CI:1.020~1.062,P<0.001)、同步近距离放疗(OR=3.768,95%CI:1.974~7.162,P<0.001)的患者急性放射性直肠损伤发生概率高;放疗前手术(OR=0.522,95%CI:0.282~0.968,P<0.001)的患者急性放射性直肠损伤发生概率低。放疗前化疗(OR=0.459,95%CI:0.265~0.794,P=0.005)的患者慢性放射性直肠损伤发生概率低;肥胖(OR=2.405,95%CI:1.081~5.347,P=0.031)患者发生慢性放射性直肠损伤的概率高。结论放疗总剂量高、同步近距离放疗的患者发生急性放射性直肠损伤的概率高,放疗前手术、放疗前化疗的患者发生急、慢性放射性直肠损伤的概率低,肥胖患者发生慢性放射性直肠损伤的概率高。

白藜芦醇减轻直肠癌放疗大鼠肠道损伤效果及作用机制研究

目的探讨白藜芦醇对直肠癌放疗大鼠肠道损伤的影响及其作用机制。方法研究对象选取健康大鼠18只,均建立直肠癌模型。建立后随机均分为对照组及白藜芦醇组,每组9只,对照组给予安慰剂,白藜芦醇组给予20 mg·kg^(-1)·d^(-1)白藜芦醇,两组均给予单剂量5Gy放疗。连续干预3周后比较两组大鼠氧化应激(ROS)标志物、炎性因子介质表达水平;观察两组大鼠肠道病理组织学变化,使用TUNEL染色观察两组肠道绒毛、隐窝细胞凋亡;使用蛋白印迹检测两组大鼠PI3K、AKT、m TOR蛋白表达。结果白藜芦醇组MDA水平显著低于对照组,HSH、CAT水平显著高于对照组,差异有统计学意义(P<0.05);白藜芦醇组TNF-α、NF-κB、IL-1β水平显著低于对照组,差异有统计学意义(P<0.05);白藜芦醇组绒毛、隐窝细胞凋亡率低于对照组,差异有统计学意义(P<0.05);白藜芦醇组PI3K、Akt和mTOR蛋白相对表达量显著低于对照组,差异有统计学意义(P<0.05);病理组织学检测显示,对照组肠黏膜部分绒毛尖端坏死,固有层白细胞炎症细胞浸润,绒毛高度和宽度杂乱,部分绒毛可见缩短、萎缩,增生和多动杯状细胞出现,出现肠道损伤,白藜芦醇组肠道损伤缓解,肠道组织结构改善。结论白藜芦醇通过抑制PI3K/Akt/mTOR通路,在改善放疗诱导的ROS产生和炎症方面具有潜在的治疗价值,可减轻放疗大鼠肠道炎症并减少大鼠肠道绒毛、隐窝细胞凋亡。白藜芦醇可能可作为一种有前景的放疗辅助剂,通过减少放疗后的肠道并发症来提高治疗效果和安全性。

An Appreciation for the Rabbit Ladderlike Modeling of Radiation-induced Lung Injury with High-energy X-Ray

Background：To evaluate the utility of rabbit ladderlike model of radiation-induced lung injury （RILI） for the future investigation of computed tomography perfusion.Methods：A total of 72 New Zealand rabbits were randomly divided into two groups：36 rabbits in the test group were administered 25 Gy of single fractionated radiation to the whole lung of unilateral lung;36 rabbits in the control group were sham-radiated.All rabbits were subsequently sacrificed at 1,6,12,24,48,72 h,and 1,2,4,8,1 6,24 weeks after radiation,and then six specimens were extracted from the upper,middle and lower fields of the bilateral lungs.The pathological changes in these specimens were observed with light and electron microscopy;the expression of tumor necrosis factor-α （TNF-a） and transforming growth factor-βl （TGF-β1） in local lung tissue was detected by immunohistochemistry.Results：（1） Radiation-induced lung injury occurred in all rabbits in the test group.（2） Expression of TNF-a and TGF-β1 at 1 h and 48 h after radiation,demonstrated a statistically significant difference between the test and control groups （each P 〈 0.05）.（3） Evaluation by light microscopy demonstrated statistically significant differences between the two groups in the following parameters （each P 〈 0.05）：thickness of alveolar wall,density of pulmonary interstitium area （1 h after radiation）,number offibroblasts and fibrocytes in interstitium （24 h after radiation）.The test group metrics also correlated well with the time ofpostradiation.（4） Evaluation by electron microscopy demonstrated statistically significant differences in the relative amounts of collagen fibers at various time points postradiation in the test group （P 〈 0.005）,with no significant differences in the control group （P 〉 0.05）.At greater than 48 h postradiation the relative amount of collagen fibers in the test groups significantly differ from the control groups （each P 〈 0.05）,correlating well with the time postradiation （r =0.99318）.Conclusions：A consistent and reliable rabbit model of RILI can be generated in gradient using 25 Gy of high-energy X-ray,which can simulate the development and evolution of RILI.