供受体混合骨髓移植GVHD反应的动物实验研究

目的 观察混合骨髓移植的GVHD反应。方法 以急性放射病BALB/C小鼠(H-2d)为受鼠,C57BL/6(H-2b)小鼠为供鼠。供体鼠骨髓和脾细胞中混合一定比例的受体鼠脾脏细胞,进行混合骨髓移植。观察移植后小鼠死亡率、白细胞系造血重建、脾结节、体内混合淋巴细胞培养、嵌合体及病理学改变,观察混合骨髓移植方式的GVHD反应。结果 异基因骨髓移植组发生明显的GVHD反应。供受鼠脾脏3:1混合骨髓移植不能明显降低GVHD反应,供受鼠脾细胞比例1:1和2:1移植组可以明显减轻GVHD反应。表现为外周血白细胞及骨髓造血恢复快,体内混合淋巴细胞反应降低及嵌合体百分率升高。结论 混合骨髓移植方式可以降低GVHD反应,并与同基因和异基因脾细胞比例有关。     

不同方式骨髓移植对辐射小鼠GVHD反应影响的研究

目的 探讨不同方式骨髓移植的移植物抗宿主反应。方法 受体C₅₇BL/6小鼠以⁶⁰Co辐射,经由尾静脉注入供体细胞。观察GVHD一般反应及病理学改变;通过解剖镜下计数脾结节、半固体琼脂法检测CFU-GM及常规计数外周WBC变化进行造血功能测定。G显带技术测定不同移植方式的嵌合体。结果 同基因与混合半相合组30 d存活率高于其他两组,异基因组GVHD反应较强,半相合组次之,混合半相合组最弱,移植13 d时同基因组与混合半相合组脾结节无明显差别,但均高于异基因或半相合组,第18天时混合半相合嵌合体与半相合组无明显差异,第30天时混合半相合组嵌合体较高。异基因、半相合、混合半相合及同基因组的体内混合淋巴细胞反应程度,依次从强到弱。除异基因组的外周血WBC及骨髓CFU-GM较低外,其余各组无明显差别。结论 半相合与混合半相和骨髓移植可以减少GVHD反应。     

咖啡酸对辐射损伤小鼠造血恢复作用的初步研究

目的 观察咖啡酸对辐射损伤小鼠造血恢复的影响。方法 建立接受4.5 Gy X射线照射的辐射损伤小鼠模型,BALB/c小鼠随机分为空白对照组,单纯照射组,CFA组,观察小鼠30天存活率、体重、外周血白细胞(WBC)、血红蛋白(HGB)、血小板(PLT)、骨髓有核细胞(BMNC)、粒细胞巨噬细胞集落形成单位(CFU-GM)、巨核细胞形成单位(CFU-MK)及脾集落形成单位(CFU-S)和脾脏指数(SI)等指标。结果 CFA组小鼠的30天存活率、体重、WBC、BMNC、CFU-GM、CFU-MK、CFU-S和SI数均明显高于单纯照射组,差异有统计学意义(P < 0.05或P < 0.01)。结论 CFA能促进辐射损伤小鼠的造血恢复。     

电离辐射对不同品系小鼠造血功能的影响

目的 探讨电离辐射对不同品系小鼠造血功能损伤的影响。方法 用¹³⁷Csγ射线对IRM-2小鼠、ICR小鼠、615小鼠进行一次性全身4.0Gy照射,建立辐射损伤模型,检测小鼠不同时间外周血白细胞(WBC)、骨髓有核细胞(BMC)及DNA的损伤情况。结果 照射后第2d,三品系小鼠的WBC、BMC及DNA降至最低值,照射后第9d,是一快速恢复期,第21d时,呈现较大幅度升高,IRM-2小鼠的WBC、BMC、DNA分别恢复到正常值的52.0%、90.8%、87.3%,ICR小鼠分别恢复到正常值的60.7%、82.1%、80.1%,615小鼠WBC、BMC恢复到正常值的50.8%、75.4%。IRM-2小鼠与ICR、615小鼠比较,差异有统计学意义(P<0.01)。结论 IRM-2小鼠经4.0Gyγ射线照射后,造血功能比ICR、615小鼠恢复的要快。     

137Cs γ射线辐照对小鼠造血及免疫功能的影响

目的 观察射线辐照对IRM-2、ICR、615、C57BL/6J四种小鼠造血及免疫功能的影响。方法 用¹³⁷Cs γ射线对四种小鼠进行4.0 Gy照射后,分别对四种小鼠的外周血分类、骨髓有核细胞及脏器指数进行测定,并检测小鼠腹腔巨噬细胞吞噬鸡红细胞的功能。结果 IRM-2小鼠白细胞总数、骨髓有核细胞及巨噬细胞吞噬率均高于615、ICR、C57BL/6J小鼠,IRM-2小鼠与615、ICR、C57BL/6J小鼠比较,差异具有统计学意义(P < 0.01)。四种小鼠的白细胞分类基本一致。照射后第4周,IRM-2小鼠的WBC、BMNC数量与ICR、615、C57BL/6J小鼠比较差异有统计学意义(P < 0.01)。结论 IRM-2小鼠免疫及造血功能较强,是较好的应用于实验研究的动物模型。     

淫羊藿甙对受照小鼠免疫与造血功能的影响

目的 探讨淫羊藿甙(ICA)对受照小鼠免疫与造血功能的恢复促进作用。方法 小鼠外周血白细胞按常规计数。骨髓CFU-GM以半固体琼脂法培养。小鼠吞噬功能以腹腔巨噬细胞吞噬百分率和吞噬指数表示。结果 与对照组比较,ICA灌喂后可明显促进外周血白细胞恢复,第6天后表现为促进骨髓CFU-GM集落形成作用,第9天后ICA表现为提高小鼠腹腔巨噬细胞吞噬百分率和吞噬指数作用。结论 ICA具有明显抗辐射作用。     

复方生白饮合剂对小鼠免疫和造血功能影响的实验研究

目的 观察中药复方生白饮合剂对小鼠免疫和造血功能的影响。方法 用⁶⁰Coγ照射和注射给予环磷酰胺的方法形成骨髓抑制和免疫低下小鼠模型,中药生白饮合剂给予口服,以外周血白细胞、骨髓有核细胞、淋转指数以及细胞肿瘤因子(TNF)、白细胞介素-6(IL-6)活性为观察指标。结果 该药对⁶⁰Coγ照射和环磷酰胺致小鼠外周血白细胞减少有明显提升作用;能促进小鼠骨髓有核细胞增殖及升高淋转指数;并能明显改善环磷酰胺和⁶⁰Coγ照射所致小鼠的TNF、IL-6活性的降低。结论 生白饮合剂有显著改善机体免疫功能和刺激骨髓造血功能的作用。     

骨髓间充质干细胞促进异基因骨髓移植后造血恢复

目的探讨骨髓间充质干细胞(BMMSC)对异基因骨髓移植小鼠造血功能恢复的影响。方法将供鼠C57BL/6(H-2b)的骨髓细胞和体外培养的BMMSC联合输给致死量照射的受鼠BalB/c(H-2d)。在移植后第1、7、14天检测受鼠外周血红细胞(RBC)、白细胞(WBC)、血小板(BPC);移植后第7、14天检测受鼠骨髓中的脾集落形成单位(CFU-S)。结果联合移植组小鼠第7、14天的外周血红细胞、白细胞、血小板、CFU-S数均显著高于单纯移植组(P<0.01)。结论BMMSC能促进异基因骨髓移植后造血功能重建。     

低聚壳聚糖对小鼠造血系统的辐射损伤防护作用研究

目的 研究低聚壳聚糖对辐射损伤小鼠造血系统的防护作用研究。方法 研究照射损伤小鼠的30d存活率及小鼠造血系统辐射损伤防护试验,指标有骨髓有核细胞数、骨髓有丝分裂指数、内源性脾结节法、脾指数测定。结果 小鼠灌服低聚壳聚糖,可以提高30 d存活率,提高平均生存天数,减轻受照小鼠骨髓有核细胞辐射损伤,促进造血干细胞的恢复。结论 低聚壳聚糖对辐照小鼠的造血系统起到一定的保护作用,从而减轻辐射对机体的损伤,达到辐射损伤防护的效果。     

三种小鼠免疫细胞对辐射敏感性差异的比较

目的 对IRM-2、ICR、615三种小鼠胸腺(Th)、脾(SP)细胞照射后辐射敏感性的差异进行比较,探讨IRM-2小鼠的辐射抗性及免疫学机制。方法 用流式细胞仪检测外周血细胞分型,PA法(FITC-Annexin V和PI标记法)检测Th、SP细胞照射后凋亡率。结果 IRM-2小鼠CD4/CD8比值低于ICR、615小鼠;CD25/CD4高于615小鼠(P<0.05),低于ICR小鼠;SP细胞凋亡率0、1、4Gy低于ICR和615小鼠,差异有统计学意义(P<0.05);Th细胞凋亡率低于ICR和615小鼠,在4Gy照射组低于615小鼠(P<0.01)。结论 IRM-2小鼠的胸腺和脾细胞对辐射不敏感,辐照后Th、SP细胞凋亡率低于ICR和615小鼠。     

Radioprotective effects of Sipunculus nudus L. polysaccharide combined with WR-2721, rhIL-11 and rhG-CSF on radiation-injured mice

This study investigated the radioprotective effect of Sipunculus nudus L. polysaccharide (SNP) in combination with WR-2721, rhIL-11 and rhG-CSF on irradiated mice. A total of 70 Imprinting Control Region (ICR) mice were divided into seven groups: the control group, the model group and five administration groups. All groups, except the control group, were exposed to a 5 Gy ⁶⁰Co γ-ray beam. Blood parameters [including white blood cell (WBC), red blood cell (RBC) and platelet counts and hemoglobin level] were assessed three days before irradiation, and the on the 3rd, 7th and 14th days after irradiation. Spleen, thymus and testicular indices, DNA contents of bone marrow cells, bone marrow nucleated cells, sperm counts, superoxide dismutase (SOD), malondialdehyde (MDA), testosterone and estradiol levels in the serum were assessed on the 14th day after irradiation. The combined administration of SNP, WR-2721, rhIL-11 and rhG-CSF exerted synergistic recovery effects on peripheral blood WBC, RBC and platelet counts and hemoglobin levels in irradiated mice, and synergistic promotion effects on spleen, thymus, testicle, bone marrow nucleated cells and sperm counts in irradiated mice. The synergistic administration increased the serum SOD activities and serum testosterone content of irradiated mice, but synergy decreased the content of serum MDA and estradiol in irradiated mice. These results suggest that the combined administration of SNP, WR-2721, rhIL-11 and rhG-CSF should increase the efficacy of these drugs for acute radiation sickness, protect immunity, hematopoiesis and the reproductive organs of irradiated-damaged mice, and improve oxidation resistance in the body.     

Amelioration of radiation-induced hematopoietic and gastrointestinal damage by Ex-RAD(R) in mice

The aim of the present study was to assess recovery from hematopoietic and gastrointestinal damage by Ex-RAD^®, also known as ON01210.Na (4-carboxystyryl-4-chlorobenzylsulfone, sodium salt), after total body radiation. In our previous study, we reported that Ex-RAD, a small-molecule radioprotectant, enhances survival of mice exposed to gamma radiation, and prevents radiation-induced apoptosis as measured by the inhibition of radiation-induced protein 53 (p53) expression in cultured cells. We have expanded this study to determine best effective dose, dose-reduction factor (DRF), hematological and gastrointestinal protection, and in vivo inhibition of p53 signaling. A total of 500 mg/kg of Ex-RAD administered at 24 h and 15 min before radiation resulted in a DRF of 1.16. Ex-RAD ameliorated radiation-induced hematopoietic damage as monitored by the accelerated recovery of peripheral blood cells, and protection of granulocyte macrophage colony-forming units (GM-CFU) in bone marrow. Western blot analysis on spleen indicated that Ex-RAD treatment inhibited p53 phosphorylation. Ex-RAD treatment reduces terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assay (TUNEL)-positive cells in jejunum compared with vehicle-treated mice after radiation injury. Finally, Ex-RAD preserved intestinal crypt cells compared with the vehicle control at 13 and 14 Gy. The results demonstrated that Ex-RAD ameliorates radiation-induced peripheral blood cell depletion, promotes bone marrow recovery, reduces p53 signaling in spleen and protects intestine from radiation injury.     

E838对环磷酰胺所致小鼠白细胞减少症的防治研究

目的 观察E838对环磷酰胺(Cy)所致IRM-2小鼠白细胞(WBC)减少症和造血功能的影响。方法 实验设对照组、E838低、中、高三个剂量组、阳性对照茜草双酯组,连续5d给药,从第3d注射给予Cy,连续3d,观察外周血白细胞、骨髓有核细胞数、内源性脾结节形成(CFU-S)、脾脏指数及胸腺指数的变化。结果 E838各组的外周血白细胞、骨髓有核细胞数与对照组相比有明显的增高,中、高剂量组与对照组比较,经统计学处理差异有显著性(P<0.01)。CFU-S与对照组比较差异有显著性(P<0.01)。脾脏指数及胸腺指数均高于对照组,高剂量组脾脏指数与对照组比较差异有显著性(P<0.05)。结论 E838有显著改善机体免疫功能和刺激骨髓造血功能的作用,能明显增加小鼠WBC的数量。     

抗VLA-4单克隆抗体动员的外周血干细胞重建辐射损伤小鼠造血的初步研究

目的 观察抗VLA-4单克隆抗体动员的外周血干细胞对辐射损伤小鼠造血重建的效果。方法 8.5 Gy~(60)Co γ射线照射的BALB/c小鼠,分别接受经生理盐水(实验1组)及抗VLA-4单克隆抗体(实验2组)动员的外周血干细胞移植,观察受体小鼠的4周存活率、外周血白细胞(WBC)、骨髓有核细胞(BMN),粒细胞巨噬细胞集落形成单位(CFU-GM)及脾集落形成单位(CFU-S)等指标。结果 实验2组小鼠的4周存活率、WBC、BMNC,CFU-GM、CFU-S数均明显高于对照组、实验1组,差异具有显著性(P<0.05或P<0.01)。结论 抗VLA-4单克隆抗体能有效动员小鼠外周血干细胞,并能成功重建辐射损伤小鼠的造血功能。     

Effects of Z-100 on mice exposed to gamma-irradiation: a preliminary report

Subcutaneous administration of Z-100 twice a week starting immediately after supralethal whole-body irradiation of mice produced a prolongation of survival time. The effect of Z-100 on the hematopoietic system was thought to have contributed to the prolongation and was thus investigated. A single subcutaneous dose of Z-100 immediately after irradiation inhibited reduction of the total number of nucleated cells in the femoral bone marrow of the treated mice, although the inhibition was not by promotion of the proliferation of specific cells but by promotion of the recovery of multiple cell lines. Treatment with Z-100 promoted colony formation in the spleen of the treated mice and CFU-S formation in the femoral bone marrow, indicating that the drug accelerated the recovery of hematopoietic stem cells. The recovery of CFU-C count was also promoted by Z-100, which suggested that the drug has a restoring effect on the recovery of granulocytic and macrophagic precursor cells. Furthermore, Z-100 produced a greater increase in the CSF activity in the serum of irradiated mice, leading to the presumption that CSF induced by Z-100 was greatly involved in promoting the recovery of the above-mentioned hematopoietic stem cells. We conclude that Z-100 prolonged survival time of irradiated mice by promoting recovery of hematopoiesis of the mice.