重组人粒细胞集落刺激因子融合蛋白对急性放射病小鼠的治疗作用

目的研究重组人血清白蛋白-粒细胞集落刺激因子融合蛋白（GW003）对急性辐射损伤小鼠的治疗作用。方法 80只BALB/c小鼠用60Coγ射线一次全身照射5.0 Gy后随机分为照射对照,GW003 1、3和9 mg/kg 4组,照射后1 h和7 d分别皮下注射生理盐水,GW003 1、3和9 mg/kg。照前1 d和照后30 d内隔日一次检测外周血细胞,照射后30 d处死小鼠取胸骨行组织病理学观察。结果 60Coγ射线5.0 Gy照射后小鼠外周血白细胞、中性粒细胞、淋巴细胞和单核细胞数急剧下降,其中1和3 mg/kg GW003组白细胞和中性粒细胞减少持续时间较照射对照组显著缩短,开始恢复时间提前,白细胞最低值明显升高。GW003 9 mg/kg组上述指标与照射对照组相比有所改善,但无显著差异。3 mg/kg GW003组小鼠单核细胞数于照射后9～13 d明显高于照射对照组。各组间外周血淋巴细胞、血小板及红细胞数无明显差异。胸骨病理组织切片显示照射后30 d各组活存小鼠骨髓造血均十分活跃。结论 GW003对60Coγ射线5.0 Gy照射所致急性放射病小鼠有明显的治疗作用。     

大剂量重组人粒细胞集落刺激因子对8.0Gy ^60Co γ射线照射小鼠长期存活率及远后效应的影响

目的探索重组人粒细胞集落刺激因子（rhG-CSF）对8.0Gy60Coγ射线照射小鼠长期存活率及远后效应的影响。方法 70只雄性C57BL/6小鼠,随机分为正常对照、照射对照及rhG-CSF大、中、小剂量治疗共5组,除正常对照组外,其他4组均接受8.0Gy60Coγ射线照射。治疗组小鼠于照射后0.5和24h两次分别皮下注射rhG-CSF1000、500和250μg/kg,随时记录各组动物存活率,照射后70、160和300d进行外周血细胞计数分析,300d时检测各组存活小鼠造血和免疫相关指标。结果照射对照组动物照后19d内全部死亡,平均存活时间（12.1±3.0）d;rhG-CSF1000μg/kg治疗组照射后30、100和300d存活率分别为86.7%、86.7%和80.0%,死亡小鼠平均存活时间较照射对照组明显延长（P〈0.01）。照后300d时,rhG-CSF1000μg/kg治疗组的外周血红细胞和血小板计数均与正常对照组没有统计学差异,骨髓混合细胞集落形成单位数量显著低于正常对照组（P〈0.01）;rhG-CSF治疗组的CD4＋/CD8＋比值倒置且250μg/kg剂量组明显低于正常对照组（P〈0.05）;rhG-CSF治疗组造血和免疫器官的组织病理切片结果显示仍然存在不同程度的病变。结论 rhG-CSF1000μg/kg治疗可以显著提高8.0Gy60Coγ射线照射小鼠存活率,但照射后300d造血和免疫系统相关指标尚未完全恢复正常。     

X射线照射对RAW264·7细胞TNF-α和NF-κB表达的影响

目的探讨X射线照射诱发小鼠巨噬细胞分泌TNF-α和NF-κB的规律。方法以8Gy X射线单次照射小鼠巨噬细胞系RAW264.7细胞,并于照后不同时间收集细胞培养上清液,采用ELISA法检测RAW264.7细胞TNF-α分泌水平;以8Gy X射线单次照射小鼠巨噬细胞系RAW264.7细胞,并于照后不同时间收集细胞并进行裂解,采用Western blot实验检测NF-кB（p65）的表达。结果 X射线照射能使小鼠巨噬细胞分泌TNF-α增加,在照射后34h达到一次分泌峰值;细胞核中NF-κB（p65）分布增多,并且随着时间的延长其核移位明显增多,照射后4h达到一次最高值。结论 X射线照射能诱发小鼠巨噬细胞TNF-α和NF-κB表达增强。     

安多霖的抗辐射损伤实验研究

目的探讨安多霖能明显提高受^60Coγ射线7Gy照射所致急性放射损伤小鼠的保护作用及与。^60Coγ射线联合给药对S180荷瘤小鼠疗效的影响。方法分别用7Gy,7．5Gy,4Gy ^60Coγ射线一次性全身照射小鼠．观察不同照射剂量对小鼠存活率,外周血WBC及抑瘤率的影响。结果安多霖明显提高受照射小鼠30d的存活率,保护系数大于1．2;明显提高小鼠外周血WBC;与^60Coγ射线7．5Gy联合给药能明显提高S180荷瘤小瘤的抑瘤率,疗效指数均大于0．85,有相加作用。     

迷迭香酸对γ射线致小鼠骨髓嗜多染红细胞微核的保护作用

目的研究迷迭香酸对γ射线致小鼠骨髓嗜多染红细胞微核的保护作用。方法以骨髓嗜多染红细胞微核形成率为观测指标,C57BL/6J小鼠经60Coγ射线1～3 Gy照射24 h后观察骨髓嗜多染红细胞微核发生率的变化以选择合适的照射剂量;C57BL/6J小鼠经60Coγ射线2Gy照射后不同时间观察骨髓嗜多染红细胞微核发生率的变化以选择照射后取骨髓的时间;2 Gy照射前经迷迭香酸处理的C57BL/6J小鼠照后24 h观察骨髓嗜多染红细胞微核发生率的变化,以确定迷迭香酸对小鼠微核保护作用的剂量效应与时间效应。结果 2 Gy照射24 h后小鼠骨髓嗜多染红细胞微核发生率增加比较明显,适合作为小剂量照射条件;照射后24 h或48 h骨髓嗜多染红细胞微核发生率增加比其他时间明显;经迷迭香酸100 mg/kg连续7次处理后的受照射小鼠骨髓细胞中,微核发生率（6.50‰）明显低于单纯照射组（23.65‰）。结论迷迭香酸对γ射线致骨髓嗜多染红细胞微核具有保护作用。     

p38抑制剂对辐射损伤小鼠中免疫细胞的作用

目的:探讨利用p38抑制剂SB203580(SB)抑制p38通路对6Gy受照小鼠免疫细胞辐射损伤的作用。方法:取雄性C57BL/6小鼠30只,随机分为对照组、照射组和SB组,每组10只。SB组和照射组小鼠接受以6Gy137Csγ射线的全身照射。SB组小鼠照射24h后腹腔注射SB(15mg/kg),每2d1次,共给药5次,其余2组小鼠腹腔注射对照溶液。小鼠受照10d后处死,取外周血计数,流式细胞仪检测CD4、CD8、B220表达,取骨髓细胞测定ROS水平。结果:照射组外周血白细胞(WBC)、CD8、B220细胞比例较对照组明显下降,骨髓ROS水平升高(P<0.01)。SB组外周血CD8比例较照射组上升,骨髓ROS水平下降(P<0.01)。结论:SB对小鼠6Gy照射后造血免疫损伤有一定的缓解作用,其机制可能与其降低照射后骨髓细胞ROS水平有关。     

五麦党黄口服液对辐射损伤小鼠防护作用的初步研究

目的研究抗辐射复方中药五麦党黄口服液(WMDH)的辐射防护作用。方法将小鼠分为5组,即正常对照组、模型组、3个给药剂量组,连续给药14 d,末次给药后3 h采用60Coγ射线一次性全身照射(7.5 Gy),于照射后记录各给药组存活时间及30 d存活率;另分组及给药剂量同前,连续给药14 d,采用60Coγ射线一次性全身照射(3.0 Gy),测定各给药组动物外周血白细胞数、胸腺、脾脏指数。结果WMDH口服液可显著延长受照射小鼠的存活时间,升高外周血白细胞数、胸腺指数、脾脏指数。结论WMDH口服液对试验小鼠核辐射损伤具有明显的保护作用,值得进一步研究和开发。     

不同剂量137Csγ-射线辐射后造血干/祖细胞辐射敏感性差异研究

摘要：目的 探讨不同剂量137Csγ-射线照射后不同时间点C57 BL/6小鼠造血细胞放射敏感性的差异。方法 选取6~8周龄雄性C57BL/6小鼠72只,完全随机法分为对照组和照射组。照射组小鼠分别接受2、4、6 Gy137Csγ射线一次性全身照射,对照组小鼠接受假照射。小鼠分别于受照后14 d、35d和56d断颈处死,取外周血进行血象测定,取骨髓细胞测定有核细胞数目和造血干/祖细胞数目。结果 不同剂量照射后小鼠的外周血常规指标有明显变化,白细胞数目明显下降,其次是血小板数目,且具有剂量效应关系;在照射后14d,2Gy、4Gy和6Gy照射组小鼠骨髓有核细胞数目与对照组比较分别下降21.9%、39.9%和54.4%（t=4.311、6.401、8.007,P<0.05）;照射后35d和56d,6Gy照射组小鼠骨髓有核细胞和造血祖细胞数目显著低于对照组（t=4.185、3.596,P<0.05）。照射后14d、35d和56d,2Gy、4Gy和6Gy照射组小鼠骨髓造血干细胞数目持续低于对照组（t=9.706、3.427~7.465,P<0.05）。结论 不同剂量137Csγ-射线照射对小鼠造血系统造成不同程度的损伤,造血祖细胞较造血干细胞辐射敏感,且辐射对造血干细胞造成的损伤是持久性的。     

硼替佐米对骨髓移植清髓照射小鼠肝及小肠内NF-κB表达的影响

目的研究硼替佐米对骨髓移植照射预处理小鼠肝及小肠内NF-κB表达的影响,进一步探讨硼替佐米防治小鼠急性移植物抗宿主病(aGVHD)的作用机制。方法骨髓移植预处理方法为BALB/c小鼠接受7.0 Gy X射线全身照射。实验分为:A组为空白对照组:未作任何处理;B组:单纯全身照射组;C组:全身照射加用硼替佐米组。观察各组小鼠的外周血白细胞计数及生存时间,Western blot法检测肝及小肠组织总蛋白及细胞核内NF-κB的表达。结果 B、C组中用于白细胞计数及生存时间观察的8只小鼠均在10 d内全部死于骨髓衰竭。照射后+1、+3、+5 d,B组肝及小肠组织总蛋白及细胞核蛋白中NF-κBp65表达均高于A组(P0.05),而C组均明显低于B组(P0.05)。结论硼替佐米可能通过一定程度上抑制照射预处理损伤所致肝脏及小肠组织中NF-κB的表达与激活,起到减轻aGVHD的作用。     

抗辐射复方中药对辐射损伤小鼠的防护作用研究

目的 对抗辐射复方中药(RFT)的辐射防护作用进行初步研究.方法 将小鼠分为5个组,分别为正常对照组、模型组、3个给药剂量组,连续给药21d,末次给药后3h采用(60)Coγ射线一次性全身照射(7.5Gy),于照射后记录各给药组存活时间、30d存活率;另,分组及给药剂量同前,连续给药14d,(60)C0γ射线一次性全身...     

Intraoral manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) radioprotective gene therapy decreases ionizing irradiation-induced murine mucosal cell cycling and apoptosis

BACKGROUND: Single or multiple intraoral administrations of manganese superoxide dismutase-plasmid/liposomes (MnSOD-PL) to C3H/HeNHsd mice receiving single fraction or fractionated ionizing irradiation to the head and neck region have been shown to significantly decrease mucosal ulceration, weight loss and to improve survival. MATERIALS AND METHODS: To elucidate the mechanism of irradiation protection by MnSOD-PL and explore possible additive or synergistic protective effects with Amifostine (WR2721), mice received a single fraction of 19, 22.5, 25 or 30 Gy, or 24 fractions of 3 Gy irradiation to the oral cavity and oropharynx. Multiple parameters of irradiation-induced toxicity were quantitated in subgroups of each irradiated group of mice treated with single or multiple administrations of intraoral MnSOD-PL and/or intravenous WR2721. RESULTS: In 19 Gy single fraction irradiated mice, MnSOD-PL treatment the day before irradiation alone or in combination with intravenous WR2721 significantly decreased the irradiation induction of mucosal cell cycling as measured by 5-bromo-2-deoxyuridine (BuDR) uptake in oral cavity mucosal cells at 48 hours and decreased ulceration of the tongue at nine days after irradiation compared to control, irradiated or irradiated, WR2721-treated mice. Mice treated in single fractions of 22.5, 25 or 30 Gy showed MnSOD-PL protection against irradiation-induced oral mucosal apoptosis and xerostomia measured in decreased saliva output. In fractionated irradiated mice, twice weekly hemagglutinin (HA) epitope-tagged MnSOD uptake in oral cavity and tongue mucosal cells was not detectably altered by daily WR2721 intravenous administration. Mice treated with both radioprotective agents (MnSOD-PL and WR2721) demonstrated a significant decrease in irradiation-induced xerostomia (measured as reduced salivary gland output volume), mucosal ulceration and improved survival. CONCLUSION: Enhanced salivary gland function in WR2721-treated mice in the absence of detectable mucosal protection, coupled with relatively low uptake of HA-MnSOD in the salivary glands of intraorally-treated mice, suggests that a combination of both radioprotective agents may prove optimally effective for the prevention of the acute and late normal tissue toxicities of fractionated radiotherapy for head and neck cancer.     

唐古特大黄多糖组分1对电离辐射损伤小鼠造血系统的影响

目的:探讨唐古特大黄多糖组分1(RTP1)对电离辐射损伤小鼠造血功能的影响。方法:采用雄性6周龄昆明种小鼠,随机分为5组:正常对照组(Normal Control,NC)、辐射对照组(Irradia-tion Control,IC)以及RTP1低剂量组(200mg/kg)、中剂量组(400mg/kg)和高剂量组(800mg/kg),采用灌胃给药方式,连续14d,NC组和IC组则给予等量的生理盐水,第14d除NC组外,各组小鼠均接受6.5Gy/只60Coγ射线照射1次,照射后继续灌胃给药,观察照射后30d小鼠生存情况,并对小鼠骨髓有核细胞数(bonemarrow cell,BMC)、骨髓DNA含量、内源性脾集落形成单位(spleen colony forming unit,CFU-S)及外周血中白细胞(white blood cell,WBC)计数进行检测。结果:与IC组比较,RTP1可提高小鼠30d存活率,并剂量依赖性地升高外周血中WBC计数、骨髓有核细胞数、DNA含量以及脾结节数。结论:RTP1对辐射小鼠的造血系统起到一定保护作用。     

Long-term effects of radioprotector WR-2721 on locomotor activity and body weight of mice following exposure to ionizing radiation

The effects of 13 Gy gamma-radiation alone and in combination with 200 mg/kg of the radioprotector S-2-(3-aminopropylamino)ethylphosphorothioic acid (WR-2721) on locomotor activity and body weight were examined in CD2F1 mice over a 10-month period. The results confirmed that WR-2721 is an excellent radioprotector against lethality. All mice receiving 13 Gy without WR-2721 died in 5-7 days. For mice that received WR-2721 alone or WR-2721 + radiation, survival at 30 days was 100% and 70%, respectively. Body weights of mice receiving WR-2721 without radiation were comparable to control animals. Body weights of animals given WR-2721 + radiation fell on days 1-5 and then increased until day 11, but remained below control values throughout the experiment. Animals in the radiation-only group did not exhibit any significant reductions in behavior until day 2 post-irradiation. Mice administered WR-2721 alone showed significantly reduced locomotor activity levels on day 0 then completely recovered within 24 h and exhibited normal body weights. Animals given WR-2721 before irradiation showed greater reductions in locomotor activity on day 0 than either the WR-2721 or radiation-only groups and recovered to control level by day 3. Beginning on day 5, they showed significant reductions in activity. Mice pretreated with WR-2721 that survived a normally lethal dose of radiation showed a 20-40% reduction in locomotor performance that recovered in 2-5 months.     

Protection by Hydrogen Against Gamma Ray‐Induced Testicular Damage in Rats

The aim of this study was to investigate the possible protective role of hydrogen‐rich saline solution (HRSS) and WR‐2721 on the testicular damage induced by irradiation. Sprague‐Dawley rats were randomly divided into four groups. Group I served as control group. Rats in group II were exposed to the irradiation. The animals in group III and IV were injected intraperitoneally with HRSS (5 ml/kg) and WR‐2721 (200 mg/kg), respectively, 15 min. before the start of gamma irradiation. Testis weight, testis dimensions, sperm count, sperm motility, apoptosis index and biochemical assays were assessed after a 4‐day initiation of irradiation. Testis weight, testis dimensions, sperm count, sperm motility in group II were significantly lower compared with those in the control group, whereas they were higher in the HRSS and WR‐2721 group. Apoptosis index was significantly increased in group II. Treatment of rats with HRSS and WR‐2721 significantly reduced the apoptosis index. On the other hand, irradiation markedly decreased activities of SOD. Activities of SOD were significantly improved when treated with HRSS and WR‐2721. Significant increase in the MDA level was observed in group II. MDA levels of group III and IV were significantly lowered when compared with group II. HRSS also played a significant role in the recovery of serum testosterone levels. The results from this experimental study suggest that hydrogen has a possible protective effect against radiation‐induced testicular damage.     

不同结构粒细胞集落刺激因子对3.0Gy ~（60）Coγ射线照射恒河猴的治疗作用

目的本研究旨在观察不同结构重组人粒细胞集落刺激因子（rhG-CSF）吉粒芬和GW003对急性放射病猴的治疗作用。方法 18只成年恒河猴用60Coγ射线全身双侧一次均匀照射3.0 Gy,实验分为照射对照、吉粒芬（rhG-CSF）和GW003治疗共3组,每组6只动物。吉粒芬治疗组动物于照射后0～13 d给予吉粒芬5μg/kg,每天一次皮下注射。GW003治疗组动物分别于照射后0和7d共两次给予GW003150μg/kg皮下注射。观察照射后动物一般体征、外周血细胞计数、骨髓细胞集落形成能力,照射后60d胸骨、脾脏、淋巴结等造血免疫组织的组织病理学改变。结果与照射对照组相比,GW003150μg/kg 1次/周连续两周给药方案可以明显升高照射动物外周血白细胞、中性粒细胞数最低值,促进骨髓造血功能恢复,缩短对症治疗中抗生素和止血药应用时间,减少输血次数,从而简化综合对症治疗措施。吉粒芬治疗组上述指标较照射对照组有明显改善,但外周血细胞和中性粒细胞数最低持续时间明显长于GW003治疗组（P〈0.05）。结论 GW003150μg/kg对3.0 Gy 60Coγ射线照射恒河猴有明显的治疗作用,该给药方案比吉粒芬5μg/kg每天一次连续14 d皮下注射给药方案更具优势。     

Relationship between radioprotective and neuromotor effects of S-2(3-aminopropyl-amino)ethylphosphorothioate (WR-2721) in mice

The radioprotective and neuromotor effects of WR-2721 were studied in male albino ICR strain mice. The protective activity was evaluated by graded doses of WR-2721 (50-400 mg/kg, IP) against whole body 60Co gamma irradiation at a single maximal lethal threshold dose rad (i.e., 1250 rad). The neuromotor effects of the drug were assayed by its action, at the same dose range as used in the protection assay, on spontaneous motor activity (SMA) and wire hanging performance (WHP). Drug doses were administered 30 min before radiation exposure and neurobehavioral testings. The results showed a dose-dependent increase in radioprotection and an inhibition in the neuromotor tasks. The radioprotective efficacy was seen at doses at which intrinsic neuromotor deficits were detected (100-400 mg/kg). A dose-related parallelism of protective efficacy and neurobehavioral toxicity (i.e., SMA inhibition and WHP disruption) was also observed. The present findings suggest that WR-2721 induces neuromotor dysfunctions along with its radioprotectivity.     

黄芪多糖与黄芪甲苷配伍对辐射损伤模型小鼠的保护作用

目的:研究黄芪多糖与黄芪甲苷配伍对辐射损伤模型小鼠的保护作用。方法:100只雌性ICR小鼠随机分为正常对照(等容生理盐水)组、黄芪多糖对照(80 mg/kg)组、黄芪甲苷对照(80 mg/kg)组、模型(等容生理盐水)组、黄芪多糖(80 mg/kg)组、黄芪甲苷(80 mg/kg)组与联合用药①、②、③、④(黄芪多糖80、40、20、80 mg/kg+黄芪甲苷20、40、80、80 mg/kg)组。灌胃给药,每天1次,连续14 d。末次给药后小鼠接受60Coγ射线(剂量:5 cy)一次性全身辐射以复制辐射损伤模型。测定小鼠30 d存活率和死亡小鼠平均存活时间;肝脏HE染色光镜下观察小鼠肝组织形态学;测定小鼠外周血白细胞数、骨髓细胞DNA含量、血清超氧化物歧化酶(SOD)活性。结果:与正常对照组比较,模型组小鼠30 d存活率降低,死亡小鼠平均存活时间缩短;小鼠肝细胞广泛肿胀,出现大滴性脂肪变、气球样变,肝脏细胞点状坏死严重,炎性因子大面积浸润组织;外周白细胞计数减少;骨髓细胞DNA含量减少;血清SOD活性减弱,差异具有统计学意义(P<0.01)。与模型组比较,联合用药①、②、③、④组小鼠30 d存活率升高,死亡小鼠平均存活时间延长,外周白细胞计数增加,骨髓细胞DNA含量增加,小鼠肝细胞形态学明显改善;联合用药①、②、③组小鼠血清中SOD活性增强,差异具有统计学意义(P<0.01)。结论:黄芪多糖与黄芪甲苷配伍是通过多靶点发挥作用,其中黄芪多糖与黄芪甲苷质量比为4∶1时配伍效果最佳。