细胞因子联合对4.5 Gy γ射线照射 比格犬的实验治疗作用

目的 观察细胞因子新的组合(rhG-CSF+rhIL-11+rhIL-2)对骨髓型急性放射病(ARS)比格犬的治疗作用。方法 以4.5 Gy  ⁶⁰Co γ射线照射比格犬制备骨髓型ARS动物模型,动物分为照射对照(5只)、综合对症(5只)和综合对症加细胞因子治疗3组(6只),通过观察动物体征、存活时间、存活数以及动物造血及胃肠道等脏器的恢复情况,分析细胞因子联合治疗效果。结果 4.5 Gy  ⁶⁰Co γ射线照射后,比格犬出现食欲下降、发热、精神状态差和柏油便等症状,照射对照组动物于照射后2周内全部死亡,平均存活(12.7±1.4)d;综合对症组呈现明显的急性放射病症状,并于照射后第33天死亡1只;而综合对症加细胞因子组动物在45 d观察期内不仅全部存活,临床症状明显改善,且其造血功能及胃、肠道等受损组织基本恢复。结论 在综合对症基础上给予rhG-CSF+rhIL-11+rhIL-2组合治疗可以有效地促进4.5 Gy ⁶⁰Co γ射线照射比格犬造血系统功能和胃肠道等重要脏器的恢复,提高受照动物存活数,并改善动物生存质量。     

肺癌常规放疗所致急性放射性肺炎与放射剂量及照射面积的关系及其防治

目的探讨常规放疗剂量和照射面积与急性放射性肺炎发病率的关系及其治疗效果.方法回顾性分析1996年12月～2001年12月183例肺癌于我科常规放射治疗情况,放射剂量均为每次2 Gy,1 /d,每周5次,总剂量为50～70 Gy.结果 19例发生急性放射性肺炎,发病率为10.4%;其中照射55 Gy以下、55～65 Gy、65 Gy以上的急性放射性肺炎的发病率分别为6%、8.7%、15.6%;平均照射面积120 cm^2以下、120 cm^2以上的急性放射性肺炎的发病率分别为8.54%、11.88%.本组肺炎经治疗的缓解率为84.21%（16/19）.结论急性放射肺炎的发病率随常规照射剂量和照射面积的增大而增加.经合理治疗可获得明显的症状及体征缓解,但应以预防为主.     

两种皮肤防护剂防治头颈部恶性肿瘤患者放射性皮肤损伤疗效对比

目的对比观察两种皮肤防护剂对头颈部恶性肿瘤患者放射性皮肤损伤的防治效果。方法回顾性分析2016年8月至2018年8月大连市中心医院放疗科收治的57例采用放射治疗皮肤防护剂(利肤宁,设为试验组)与53例采用三乙醇胺乳膏(设为对照组)预防放射性皮肤损伤的行放射治疗的头颈部恶性肿瘤患者的病历资料,两组患者除外用药不同外,其他治疗方法均相同,对比两组患者放射治疗期间放射性皮肤损伤程度及不同放射剂量时放射性皮肤损伤发生情况。结果 (1)放射治疗1周后,试验组患者中皮肤出现1级损伤者18例、2级损伤者37例、3级损伤者2例,对照组患者中皮肤出现1级损伤者10例、2级损伤者29例、3级损伤者13例、4级损伤者1例,两组对比,P0.05,差异具有统计学意义。(2)试验组患者在放射剂量为20 Gy以下时均未出现皮肤损伤;在放射剂量为20～40 Gy时,有18例患者出现皮肤损伤;在放射剂量为40 Gy以上时,有39例患者出现皮肤损伤。对照组患者在放射剂量为20 Gy以下时,有1例患者出现皮肤损伤;在放射剂量为20～40Gy时,有29例患者出现皮肤损伤;在放射剂量为40 Gy以上时,有23例患者出现皮肤损伤。两组患者接受不同放射剂量时皮肤损伤发生情况对比,P 0.05,差异具有统计学意义。结论利肤宁可有效延长头颈部恶性肿瘤患者放射治疗期间放射性皮肤损伤的发生时间,降低皮肤损伤程度,疗效显著,临床应用价值较高。     

大剂量全身照射比格狗生物效应观察

目的 :为极重度骨髓型急性放射病实验治疗提供依据 ,观察了不同剂量照射比格狗的生物效应。方法 :60 Coγ辐射源分别照射 6 .5 ,5 .5 ,5 .0 ,4.5 ,3.5 ,2 .5Gy ,照射剂量率为 7.2 2 4× 10 _2 C/(kg·min)。观察照射动物的一般临床表现、外周血细胞计数、骨髓细胞培养。结果 :所有比格狗于照射后 0 .5～ 2h均有呕吐。 6 .5Gy照射组动物于照射后第 2天出现腹泻 ,并伴有白色黏液 ,其中 3只动物出现血水样便或咖啡样便。 5 .5Gy组有个别动物出现水样便 ,而 4.5Gy以下剂量照射组动物出现一般稀便。比格狗除 2 .5Gy组有一只动物活存外 ,其余均死亡 ,各组死亡动物平均活存时间依剂量的大小分别为 5 .0 ,8.0 ,9.3,9.5 ,10 .5和 14.1d。照射后 1d骨髓造血祖细胞集落数随照射剂量的增加而明显减少。照射后外周血白细胞和血小板数最低值出现时间随照射剂量的增大而提前 ,且剂量效应关系显著。结论 :对临床症状、外周血白细胞及活存时间的分析结果表明 ,比格狗的极重度骨髓型急性放射病 (偏轻 )模型的全身照射剂量为 4.5～ 5 .0Gy。     

不同剂量水平椎体IMRT对比格犬椎体骨细胞的损伤作用

目的 通过比较不同剂量水平椎体适形调强放疗(IMRT)对成年比格犬椎体骨细胞的损伤作用,初步探讨一次全椎体IMRT的安全剂量范围。方法 选取纯种比格犬30只按随机数字表法平均分为5组,以全椎体IMRT的治疗方式分别对5组比格犬胸9~10椎体给予0、40、50、60和70 Gy剂量的照射,于照后3个月处死,取相同部位的胸9~10节段椎体骨进行HE染色、电镜观察后,免疫组织化学法定量检测椎体中血管内皮细胞生长因子(VEGF)蛋白的表达,TUNEL法定量检测椎体骨中凋亡骨细胞。结果 HE染色结果提示随着IMRT剂量的增大,比格犬椎体骨空骨陷窝率增加明显(F=2.57,P<0.05),骨小梁断裂程度增加,但面积未见明显下降(P> 0.05);电镜结果提示40 Gy IMRT组部分骨细胞出现凋亡,而50 Gy及以上剂量IMRT组绝大多数骨细胞凋亡。TUNEL表达结果提示40 Gy IMRT组骨细胞凋亡率低于50 Gy及以上剂量组骨细胞凋亡率(F=3.52,P<0.05),50 Gy及以上剂量组骨细胞凋亡率差异无统计学意义(P>0.05)。50 Gy以上组的VEGF蛋白表达高于40 Gy组(F=3.64,P<0.05),但50、60、70 Gy组之间差异无统计学意义(P>0.05)。结论 50 Gy可作为临床选择治疗总剂量界限的参考标准。     

单倍体外周血造血干细胞移植治疗肠型急性放射病

目的 探讨单倍体外周血造血干细胞移植在救治肠型急性放射病中的作用.方法 山东"10·21"辐射事故患者"A"受到60Co γ射线全身相对均匀照射达20～25Gy,诊断肠型急性放射病.照射后3天全环境保护、抗感染、刺激因子、HLA配型等,给予"环磷酰胺(CTX) ATG 氟达拉滨"预处理,7天行同胞间单倍体外周血造血干细胞移植,采用"环孢霉素A(CsA)/FK506 骁悉(MMF) CD25 间充质干细胞(MSC)"预防移植物抗宿主病(GVHD),并给予对症支持治疗.结果 17天白细胞开始上升,19天重建造血:白细胞数＞5×109/L,中性粒细胞绝对值＞4×109/L,血小板＞30×109/L,网织红细胞恢复正常.多种检测证明稳定完全植入,未发生GVHD.19天发生肺部细菌及真菌混合感染,放射损伤及肺部感染逐渐加重,33天死于多脏器功能衰竭(MOF).结论 本例是国内肠型急性放射病造血干细胞移植首次成功报告,延长了存活时间,对类似病例的救治有重要指导意义.     

骨髓间充质干细胞对大鼠急性放射性肝损伤修复的研究

目的 探讨骨髓间充质干细胞(BMSCs)对大鼠急性放射性肝损伤的修复作用。方法 雌性SD大鼠12只,肝右叶接受单次6MVX射线20Gy照射,建立急性放射性肝损伤模型;随机分成2组,干预组注射雄性大鼠BMSCs悬液,对照组注射等量生理盐水。4周后观察大鼠肝组织的病理形态学改变,采用原位杂交技术检测肝脏中性别决定基因Y(SRY)及免疫组织化学技术检测ɑ-平滑肌肌动蛋白(ɑ-SMA)的阳性表达。结果 两组大鼠肝右叶组织中均可见汇管区炎性反应及肝实质细胞的损伤,但干预组的损伤程度比对照组轻。干预组大鼠肝右叶中检测到的SRY阳性细胞多于肝左叶(t=3.77,P＜0.05),ɑ-SMA的阳性表达率低于对照组(t=2.25,P＜0.05)。结论 单次20Gy照射可以造成大鼠肝右叶急性放射性损伤;SRY阳性细胞可以被征募到大鼠的放射性肝损伤部位,在一定程度上可能减轻放射性肝纤维化的发生。     

异基因外周血造血干细胞移植治疗极重度骨髓型和肠型急性放射病的临床报告

目的 探讨异基因外周血造血干细胞移植在肠型和极重度骨髓型放射病救治中的作用和地位.方法 山东"10·21" 60Co 辐射事故中2例病人受到意外照射,病例A受照射剂量20～25Gy,诊断为"肠型放射病",病例B受照射剂量9～15Gy,诊断为"极重度骨髓型放射病".经联合环磷酰胺、抗淋巴细胞球蛋白和氟达拉滨预处理,2例分别行HLA半相合及全相合外周血造血干细胞移植.采用环孢霉素A和骁悉方案(病例A加用CD25单抗和供者间充质干细胞)预防移植物抗宿主病(GVHD).结果 2例均移植成功,供体完全存活,移植后9～11天白细胞开始恢复,2周后白细胞恢复正常、骨髓造血重建成功.2例均未发生移植排斥和GVHD.病例A照射后33天死于败血症和多器官功能衰竭.病例B照射后75天死于心衰为主的多器官功能衰竭.结论 HLA相合及半相合外周血造血干细胞移植救治极重度骨髓型和肠型急性放射病是完全可能和可行的,联合免疫抑制剂预处理对促进供体稳定植入是必要的,环孢霉素A、骁悉和CD25单抗及供者间充质干细胞对预防GVHD有重要作用.     

细胞因子联合对4.5Gyγ射线照射比格犬造血损伤的治疗作用

目的 观察细胞因子组合对4.5 Gy γ射线照射比格犬造血系统损伤的治疗效果,为极重度骨髓型急性放射病的临床救治提供实验依据。方法 16只比格犬均给予4.5 Gy ⁶⁰Co γ射线全身照射,随机分为照射对照、综合对症和细胞因子3组。细胞因子组动物在综合对症支持治疗的基础上应用rhG-CSF、rhIL-11和rhIL-2联合治疗。2 d检测1次外周血象,分别于照射前4 d,照射后1和45 d收集骨髓和外周血进行造血细胞集落培养,制备胸骨病理切片观察组织形态学改变。结果 照射后各组动物外周血各类细胞数急剧下降,细胞因子联合治疗可提高白细胞最低值(1.04×10⁹/L,而照射对照组和综合对症组分别为0.28×10⁹/L和0.68×10⁹/L),缩短血小板减少持续时间(细胞因子组24 d,综合对症组33 d),使红细胞维持在正常值范围;照射后1 d骨髓及外周血中造血干细胞集落形成率明显下降,照射后45 d 2个治疗组造血干细胞集落数均恢复为照射前水平;照射对照组动物骨髓造血细胞完全消失,细胞因子治疗使得骨髓造血功能完全恢复,与照射前水平比较差异无统计学意义。结论 rhG-CSF、rhIL-11和rhIL-2联合应用可提高极期时外周血白细胞最低值,加速白细胞、血小板和红细胞恢复,促进4.5 Gy γ射线照射犬体内残留造血干/祖细胞的增殖、分化和成熟,从而加速造血功能的重建。rhG-CSF、 rhIL-11和rhIL-2不失为治疗极重度骨髓型急性放射病的有效措施。     

异基因骨髓源间充质干细胞对极重度放射损伤小鼠造血功能重建的影响

目的 探讨异基因骨髓源间充质干细胞(MSC)输注对极重度放射损伤小鼠造血功能重建的影响.方法 以C57BL/6(H-2b)雄性小鼠为供体制备MSC单细胞悬液.取雌性BALB/c(H-2d)小鼠120只作为受体,随机分为MSC-A组、MSC-B组、MSC-C组和PBS组(n=30).均接受60Co γ射线致死剂量(8Gy)照射,前3组小鼠于照射后2h分别经尾静脉输注MSC 1×106、1×105、5×104/R,PBS组在相同时间点经尾静脉输注等体积(0.4ml)PBS.观察小鼠的生存情况及外周血白细胞(WBC)、血红蛋白(HGB)、血小板(PLT)的变化,进行骨髓单个核细胞、粒-单系祖细胞(CFU-GM)及脾集落形成单位(CFU-S)计数,对Y染色体进行检测,并观察小鼠股骨骨髓的病理学变化.结果 各组小鼠经致死剂量照射后,WDC、HGB和PLT均迅速下降,PBS组小鼠于照射后17d内全部死亡.MSC-A、MSC-B、MSC-C组小鼠的外周血WBC、HGB、PLT在2周左右开始逐渐恢复,观察至56d,各组小鼠的生存率分别为61.9%、47.6%、38.0%.MSC各治疗组小鼠的生存率、骨髓单个核细胞、CFU-GM、CFU-S均明显高于PBS组(P<0.05),前述各项指标均随MSC输注数量的增加而增加.移植后10d,MSC各治疗组小鼠骨髓中均可检测到Y染色体,但仅在移植后初期短暂植入.MSC输注后42d,MSC各治疗组骨髓增生活跃.结论 异基因来源的骨髓源MSC单独输注可促进极重度放射损伤小鼠造血功能重建;随着MSC输注数量的增加,其促造血重建功能增强.     

The influence of changing dose rate patterns from inhaled beta-gamma emitting radionuclide on lung cancer

Purpose: Dose and dose rate are both appropriate for estimating risk from internally deposited radioactive materials. We investigated the role of dose rate on lung cancer induction in Beagle dogs following a single inhalation of strontium-90 (⁹⁰Sr), cerium-144 (¹⁴⁴Ce), yttrium-91 (⁹¹Y), or yttrium-90 (⁹⁰Y). As retention of the radionuclide is dependent on biological clearance and physical half-life a representative quantity to describe this complex changing dose rate is needed.

Materials and methods: Data were obtained from Beagle dog experiments from the Inhalation Toxicology Research Institute. The authors selected the dose rate at the effective half-life of each radionuclide (DR_ef).

Results: Dogs exposed to DRef (1–100?Gy/day) died within the first year after exposure from acute lung disease. Dogs exposed at lower DRef (0.1–10?Gy/day) died of lung cancer. As DR_ef decreased further (<0.1?Gy/day ⁹⁰Sr, <0.5?Gy/day ¹⁴⁴Ce, <0.9?Gy/day ⁹¹Y, <8?Gy/day ⁹⁰Y), survival and lung cancer frequency were not significantly different from control dogs.

Conclusion: Radiation exposures resulting from inhalation of beta-gamma emitting radionuclides that decay at different rates based on their effective half-life, leading to different rates of decrease in dose rate and cumulative dose, is less effective in causing cancer than acute low linear energy transfer exposures of the lung.     

Effect of subsequent acute-dose irradiation on cell survival in vitro following low dose-rate exposures

PURPOSE: Following acute irradiation, excess radiosensitivity is generally seen at doses <1 Gy, a phenomenon termed "low-dose hyper-radiosensitivity" (HRS). A very strong, HRS-like inverse dose-rate effect has also been described following continuous low dose-rate (LDR) irradiation at <30 cGy h(-1). We report on the sequential irradiation of a cell line by such LDR exposures followed by low acute doses, where either treatment individually would elicit a hypersensitive response. The aim was to determine if a prior LDR exposure would remove the HRS normally seen in response to very small acute radiation doses. MATERIALS AND METHODS: T98G human glioma cells were given single continuous LDR exposures of 5-60 cGy h(-1) using a (60)Co gamma-source. At intervals of 0 or 4 h following LDR irradiation, cells were further irradiated with a range of acute doses using 240-kVp X-rays. The response to the combined treatment was assessed using high-precision clonogenic cell survival assays, and the amount of HRS at acute doses <1 Gy was determined. RESULTS: LDR at > or = 60 cGy h(-1) to total doses up to 5 Gy in asynchronously growing cells did not remove HRS in the subsequent acute-dose survival curve. In confluent cultures, subsequent acute-dose HRS was not present after an LDR dose of 5 Gy at either 60 or 30 cGy h(-1), but returned if a 4-h interval was left between LDR and acute-dose irradiation. In confluent cultures, acute-dose HRS remained for LDR treatments at 5 or 10 cGy h(-1) or if the total dose was 2 Gy. Taking all cultures and dose-rates together, the "degree" of acute-dose HRS, as measured by alpha(s), was significantly greater in cells irradiated at LDR to a total dose of 2 than of 5Gy. CONCLUSIONS: Initial LDR exposure can affect a subsequent HRS response. HRS is reduced after LDR exposures at greater dose intensity, but can recover again within 4 h of completion of LDR exposure. This suggests that processes determining increased resistance to small acute doses (removal of HRS) might be governed by the level of repairable DNA lesions.     

GM—CSF和rhBM—2m对小鼠急性放射损伤治疗作用的对？…

目的　研究和比较重组人骨形成蛋白 (rhBMP 2m)、GM CSF对照射后小鼠造血损伤的修复作用。方法　rhBMP 2m用分子生物学方法由大肠杆菌中获得 ;该实验中rhBMP 2m对照射后动物的影响 ,通过观察动物的 30天活存率表示。结果　照射对照组小鼠的 30天活存率为 0 ,平均活存天数为 (9 1± 2 2 )d ;GM SCF治疗组小鼠的 30天活存率为 2 0 0 % ,平均活存天数为 (1 1 5±1 9)d ,rhBMP 2m治疗组小鼠的 30天活存数为 4 ,活存率为 40 % ,平均活存天数为 (1 3 2± 6 1 )d。结果显示GM CSF和rhBMP 2m均能提高受照小鼠的活存率 ,并延长活存时间 ,而且后者优于前者(P <0 0 5)。结论　rhBMP 2m对小鼠急性放射损伤具有治疗作用 ,初步观察其优于GM CSF     

Evaluation of the radioprotective effect of bael leaf (Aegle marmelos) extract in mice

PURPOSE: To investigate the radioprotective activity of a leaf extract of bael leaf (Aegle marmelos) (AME) in mice exposed to different doses of gamma-radiation. MATERIALS AND METHODS: The acute toxicity of AME was evaluated in Swiss albino male mice administered various intraperitoneal single doses of AME. For radioprotection studies, mice were administered different doses, 0, 5, 10, 15, 20 or 40 mg kg(-1), of AME or sterile physiological saline intraperitoneally once daily consecutively for 5 days before exposure to 10 Gy 60Co gamma-radiation or five doses of 15 mg kg(-1) AME before exposure to 6, 7, 8, 9, 10 or 11 Gy. The animals were monitored for symptoms of radiation sickness and mortality up to 30 days post-irradiation. Glutathione and lipid peroxidation were estimated in the surviving animals of both groups on day 31 post-irradiation. RESULTS: AME was non-toxic up to a single dose of 1750 mg kg(-1). The optimum radioprotective dose was five consecutive doses of 15 mg kg(-1) AME, where the highest survival to 10 Gy radiation was observed. The irradiation caused a dose-dependent decline in survival, while treatment of mice with AME enhanced survival. The dose reduction factor was 1.15. Irradiation caused a dose-dependent decline in the level of glutathione accompanied by an elevation in lipid peroxidation. AME pretreatment arrested glutathione decline and lipid peroxidation significantly. CONCLUSION: AME treatment reduced the symptoms of radiation-induced sickness and increased survival. The radioprotective action might be due to free-radical scavenging and arrest of lipid peroxidation accompanied by an elevation in glutathione.     

间充质干细胞促进半相合骨髓移植治疗急性放射病小鼠的实验研究

目的 探讨骨髓间充质干细胞(MSCs)促进半相合造血干细胞移植(haploid-SCT)治疗急性放射病小鼠的作用及机制。方法 ⁶⁰Co γ射线照射BALB/C(H-2^d)雌性小鼠8Gy,单独输注半相合CB6F1(H-2 bd) 雄性小鼠骨髓细胞1×10⁹/kg(I组),或联合CB6F1 雌性小鼠MSCs不同数量级1.5×10⁸/kg (a组)、5×10⁷/kg (b组)和2.5×10⁷/kg (c组)治疗,比较放射病小鼠的生存分析。同时,MSCs组小鼠尾静脉输注经cm-DiI膜染剂标记的CB6F1雌性小鼠MSCs和CB6F1雄性小鼠的骨髓细胞,与只输注CB6F1骨髓细胞的对照组比较,观察移植后不同时间供者细胞在受者骨髓的植入率、供者MSCs在受者体内发布、外周血象、T淋巴细胞亚群、胸骨骨髓病理和慢性移植物抗宿主病(GVHD)发生情况。结果 a组小鼠早期死亡率增加;b和c组存活率高于I组(P<0.05),但二组之间差异无统计学意义。移植后30 d,MSCs组受者骨髓的sry基因高于对照组。移植后MSCs主要集中在胸腺、骨髓、肝和小肠中,有形态改变。MSCs组的白细胞、血小板恢复较快。照射后15和30 d,MSCs组小鼠骨髓腔中的巨核细胞明显高于对照组。移植后7、14和30 d,MSCs组CD3高于对照组(P<0.05);移植后14和30 d,MSCs组CD4阳性细胞率和CD4/CD8值高于对照组(P<0.05)。MSC组慢性GVHD症状出现较对照组晚30 d。结论 MSCs通过促进干细胞植入,改善造血微环境,促进造血恢复,加快T淋巴细胞的恢复,延缓GVHD的发生时间和促进放射损伤的组织器官的修复,加强了半相合骨髓移植对急性放射病的治疗作用。     

Effect of subsequent acute-dose irradiation on cell survival in vitro following low dose-rate exposures

Purpose : Following acute irradiation, excess radiosensitivity is generally seen at doses <1 Gy, a phenomenon termed 'low-dose hyper-radiosensitivity' (HRS). A very strong, HRS-like inverse dose-rate effect has also been described following continuous low dose-rate (LDR) irradiation at <30 cGy h -1. We report on the sequential irradiation of a cell line by such LDR exposures followed by low acute doses, where either treatment individually would elicit a hypersensitive response. The aim was to determine if a prior LDR exposure would remove the HRS normally seen in response to very small acute radiation doses. Materials and methods : T98G human glioma cells were given single continuous LDR exposures of 5-60 cGy h -1 using a 60 Co γ-source. At intervals of 0 or 4 h following LDR irradiation, cells were further irradiated with a range of acute doses using 240-kVp X-rays. The response to the combined treatment was assessed using high-precision clonogenic cell survival assays, and the amount of HRS at acute doses <1 Gy was determined. Results : LDR at ≥60 cGy h -1 to total doses up to 5 Gy in asynchronously growing cells did not remove HRS in the subsequent acute-dose survival curve. In confluent cultures, subsequent acute-dose HRS was not present after an LDR dose of 5 Gy at either 60 or 30 cGy h -1, but returned if a 4-h interval was left between LDR and acute-dose irradiation. In confluent cultures, acute-dose HRS remained for LDR treatments at 5 or 10 cGy h -1 or if the total dose was 2 Gy. Taking all cultures and dose-rates together, the 'degree' of acute-dose HRS, as measured by α s, was significantly greater in cells irradiated at LDR to a total dose of 2 than of 5Gy. Conclusions : Initial LDR exposure can affect a subsequent HRS response. HRS is reduced after LDR exposures at greater dose intensity, but can recover again within 4 h of completion of LDR exposure. This suggests that processes determining increased resistance to small acute doses (removal of HRS) might be governed by the level of repairable DNA lesions.     

^18F-FDG PET/CT显像与心脏磁共振成像对Beagle犬局部辐射后心脏损伤的诊断

目的探讨^18F-脱氧葡萄糖(FDG)PET/CT显像与心脏磁共振成像(CMR)对Beagle犬局部放射性心脏损伤(RIHD)的诊断价值。方法将24只1岁龄健康雄性Beagle犬按照随机数字表法分为对照组及照射后3、6和12个月组,每组各6只;其中各照射组左心室前壁行单次20 Gy调强放疗。对全部犬行^18F-FDG PET/CT心肌代谢显像和CMR检查,计算^18F-FDG摄取增高区平均标准摄取值(SUVmean)及面积。全部检查结束后1周处死实验犬,取心脏进行Masson染色及电子显微镜检查。采用单因素方差分析比较组间差异。结果对照组心肌^18F-FDG几乎不摄取,照射后3个月即可见犬心肌^18F-FDG摄取增加,照射后3、6和12个月组的心肌SUVmean分别为5.90±1.31、4.66±2.21和3.21±0.82,与对照组(1.13±0.21)的差异有统计学意义(F=11.81,P<0.05);照射组^18F-FDG摄取增高面积随着照射后时间延长逐渐下降(F=195.74,P<0.01)。CMR示照射后6和12个月组的心肌灌注降低、进行性纤维化加重;与对照组相比,照射后6和12个月组的舒张末期容积(EDV)和收缩末期容积(ESV)增加(F=15.479和16.908,均P<0.01),而左心室射血分数(LVEF)下降(F=63.715,P<0.01)。Masson染色发现照射后心肌纤维化进行性加重;电子显微镜检查示照射后心肌线粒体变性肿胀,线粒体数量进行性减少。结论照射后局部心肌^18F-FDG摄取增高对于RIHD的危险性有预测价值,^18F-FDG PET/CT显像能早于CMR发现RIHD。     

局部屏蔽对裂变中子照射狗的防护作用——Ⅱ.照射剂量对防护效果的影响

在使狗产生轻度肠型(3Gy 照射)、极重度骨髓型(3和2.65Gy 照射)和重度骨髓型(2Gy 照射)中子急性放射病的全身照射剂量条件下,使用含硼橡胶屏蔽狗的下腹+骨盆部,均可使病情减轻。3Gy 和2.65Gy 时减轻为重度骨髓型放射病,2Gy 时减轻为中度骨髓型放射病。从屏蔽狗的活存率、临床症状及外周血白细胞数看,剂量低时比剂量高时的屏蔽效果明显。     

慢性镉染毒及联合辐射对大鼠的基因毒性作用

目的 探讨慢性镉染毒及联合辐射对大鼠的基因毒性.方法 雄性SD大鼠分设空白对照组、0.1 mg CdCl2·kg-1·d-1低剂量镉染毒组、0.5 mg CdCl2·kg-1·d-1高剂量镉染毒组、单纯照射组、低剂量镉染毒+照射组和高剂量镉染毒+照射组.腹腔注射镉染毒连续8周,1次/d,然后给予2 Gy γ照射.于照射后第10天或受照即日后继续染镉4周,心脏取血,采用多核细胞法检测外周血淋巴细胞微核率和hprt基因突变率,同时检测外周血白细胞数量变化和血镉含量.结果 大鼠低剂量镉染毒8周和12周组未观察到外周血细胞损伤,而辐射诱导的微核率(F=26.74,P<0.01和F=14.13,P＜0.05)和hprt基因突变率(F=6.60,P＜0.05)显著降低;高剂量镉染毒8周和12周组与空白对照组比较,外周血白细胞数显著增高(F=8.74,P＜0.01和F=13.11,P=0.000),淋巴细胞微核率(F=26.74,P＜0.05和F=14.13,P=0.000)和hprt基因突变率(F=6.60,P＜0.05和F=12.83,P＜0.05)明显增加,而高剂量镉染毒+照射组的基因毒性又显著高于单纯高剂量镉染毒组或单纯照射组,表现出联合毒性效应.结论 慢性、低剂量镉染毒诱导外周血淋巴细胞对辐射产生适应性效应,血镉浓度增加到613～678 μg/L时能刺激白细胞显著增加并与辐射联合作用加重对淋巴细胞的基因毒性.

Abstract：

objective To investigate the effects of chronic cadmium exposure and cadmium exposure combined with γ-ray irradiation on the peripheral lymphocytes and their genotoxicity on hprt gene.Methods Ninety-six SD rats were randomly divided into 6 equal groups:①normal control group,②lowdose cadmium exposure group undergoing intraperitoneal injection of 0.1 mg CdCl2·kg-1·d-1 for 8 weeks,③high-dose cadmium exposure group undergoing intraperitoneal injection of 0.5 mg CdCl2·kg-1·d-1 for 8 weeks,④pure irradiation group exposed to whole-body γ-ray irradiation at the dose of 2 Gy for one time,⑤low-dose cadmium exposure combined with irradiation group undergoing intraperitoneal injection of 0.1 mg CdCl2·kg-1·d-1 for 8 weeks and then whole-body 2 Gy γ-ray irradiation,and ⑥high-dose cadmium exposure combined with whole-body 2 Gy γ-ray irradiation group undergoing intraperitoneal injection of 0.5 mg CdCl2·kg-1·d-1 for 8 weeks and then whole-body 2 Gy γ-ray irradiation.Ten days after the irradiation cardiac blood samples were collected from some of the rats to culture the peripheral lymphocytes to detect the micronucleus rate and hprt mutant frequency of lymphocytes bv multinucleated cell assay.The other rats underwent continuous Cd exposure for 4 weeks after γ-ray irradiation and then cardiac blood samples were collected to detect the micronucleus rate and hprt mutant frequencv of lymphocytes.Meanwhile,the amount of white blood cells(WBC)was counted and the blood cadmium concentration was measured by ICP-MS.Results The numbers of WBC in the peripheral blood at different time points of the high dose cadmium group were significantly higher than those of the normal control group(F=8.74.P<0.01 and F=13.11,P=0.000).The micronucleus rate at difierent time points of the pure irradiation group were significantly higher than those of the control group( F = 26. 74 ,P =0. 000 and F = 14. 13, P = 0. 000). The micronucleus rates of the high-dose cadmium group were significantly higher than those of the control group( F = 26. 74 ,P <0. 05 and F = 14. 13 ,P = 0. 000 ). The micronucleus rates of the low-dose cadmium + irradiation group were significantly lower than those of the pure irradiation group( F = 26. 74, P < 0. 01 and F = 14. 13, P < 0. 05 ). The micronucleus rates of the highdose cadmium + irradiation group were significantly higher than those of the pure irradiation group ( F =26.74,P =0. 000 and F = 14. 13 ,P =0. 000). The hprt mutation rates at different time points of the pure irradiation group were significantly higher than those of the normal control group( F = 6.60, P < 0. 01 and F = 12.83 ,P = 0. 001 ). The hprt mutation rates of the high-dose cadmium group were significantly higher than those of the control group ( F = 6. 60, P < 0. 05 and F = 12.83, P < 0.05 ), but not significantly different from those of the pure irradiation group. However, the hprt mutation rates of the high-dose cadmium + irradiation group were significantly higher than those of the pure irradiation ( F = 12. 83, P =0. 000) and high-dose cadmium group( F = 6.60,P < 0.05 and F = 12. 83, P < 0.05 ). The hprt mutation rates of the low-dose cadmium + irradiation group were significantly lower than those of the pure irradiation ( F = 6. 60, P < 0. 05 ) , but not significantly different from those of the control group. Conclusions Chronic exposure to low dose cadmium induces the adaptive response of lymphocytes to radiation. The cadmium in blood at the level of 613-678 μg/L induces leukocytosis and chronic exposure to high dose cadmium combined with irradiation leads to increased genotoxicity of lymphocytes.