酵母β-葡聚糖加锌复合配方对免疫抑制幼龄小鼠的免疫调节作用

目的:探究酵母β-葡聚糖加锌复合配方对环磷酰胺诱导免疫抑制幼龄小鼠的免疫调节作用。方法:48只3周龄BALB/c小鼠,随机分成空白组、模型组和复合物组。复合物组灌以由酵母β-葡聚糖和锌组成的复合物(相当于酵母β-葡聚糖:90 mg/kg/d、锌:2.8 mg/kg/d),空白组、模型组灌以等体积蒸馏水,模型组、复合物组在试验的第14、15 d以腹腔注射40 mg/kg环磷酰胺构建免疫低下模型,28 d后,再将小鼠分为两组,第Ⅰ组用于测定免疫器官指数、免疫细胞数目和活性以及细胞因子。第Ⅱ组用于血清溶血素实验和溶血空斑实验。结果:与模型组相比,酵母β-葡聚糖和柠檬酸锌复合配方能显著（P<0.05）提高小鼠免疫器官系数,促使脾淋巴细胞增殖和增加杯状细胞数量,极显著（P<0.01）提高半数溶血值（serum half hemolysis value, HC₅₀）、溶血空斑数、NK细胞活性,增加外周血中α肿瘤坏死因子（Tumor necrosis factor-α, TNF-α）、γ干扰素（interferon-γ, IFN-γ）浓度、白细胞数量,增加派氏结。结论:酵母β-葡聚糖加锌复合配方具有提高体液免疫、NK细胞活性,并增强肠黏膜免疫的作用。     

同胞相合异基因造血干细胞移植治疗恶性血液病的疗效

目的探讨同胞相合异基因造血干细胞移植治疗恶性血液病的临床疗效。方法将26例恶性血液病患者按移植前疾病状态分为2组：高危组11例和标危组15例。2组患者均采用外周血同胞相合异基因造血干细胞移植。预处理方案：高危组采用全身照射＋环磷酰胺,标危组采用白消安＋环磷酰胺;移植物抗宿主病的预防：2组均采用环孢素A＋短程甲氨蝶呤,或加霉酚酸脂。观察2组患者造血重建和急、慢性移植物抗宿主病、巨细胞病毒活动性感染/巨细胞病毒病、移植复发及移植相关死亡及无病生存等情况。结果 2组患者移植后均获得造血重建,均为完全供体嵌合型。2组患者移植后14例发生急性移植物抗宿主病（aGVHD）,累积发病率为53.8%（14/26）。9例发生慢性移植物抗宿主病（cGVHD）,累积发病率为45.0%（9/20）。2组患者移植后有20例（76.9%）出现巨细胞病毒血症,无一例患者发生巨细胞病毒病。标危组复发率与高危组比较差异无统计学意义（6.7%vs 18.2%,P〉0.05）。标危组移植相关病死率与高危组比较差异有统计学意义（13.3%vs 54.5%,P〈0.05）。高危组和标危组患者1、3年累积无病生存率分别为30.3%、85.1%和15.2%、68.1%（均P〈0.05）。结论移植前疾病状态是影响移植疗效的重要因素,移植物抗宿主病的发生对移植后疾病的复发及生活质量有重要的影响。     

螺旋藻多糖对环磷酰胺所致小鼠骨髓抑制的实验研究

目的 研究螺旋藻多糖对小鼠骨髓造血功能的增强作用。方法 将小鼠分成4 组:对照组、环磷酰胺模型组、螺旋藻多糖30 mg·kg^-1、螺旋藻多糖60mg·kg^-1。模型组、螺旋藻多糖组腹腔注射环磷酰胺造模。同时螺旋藻多糖组灌胃螺旋藻多糖, 对照组、模型组灌胃生理盐水。结果 螺旋藻多糖在30、60mg·kg^-1剂量下, 对环磷酰胺所致小鼠外周血象、骨髓有核细胞均有改善(P <0.01) 。对骨髓细胞微核增加有明显的拮抗作用(P <0.05) 。螺旋藻多糖组小鼠骨髓细胞染色体畸变率较模型组显著降低,其抑制率分别为51.2%、61.5 %。结论 螺旋藻多糖可抑制环磷酰胺诱发的小鼠造血功能损伤。     

顺铂与环磷酰胺联合应用剂量优化的实验研究

目的: 观察低剂量顺铂(DDP)和环磷酰胺(DTX)联合用药治疗恶性肿瘤疗效及其对免疫器官的毒性。方法: 采用小鼠肉瘤S180进行体内实验,观察两药单独及联合使用对小鼠S180 及胸腺和脾脏的影响。结果: DDP组和不同剂量的DTX 配伍应用与DDP组相比抑瘤率分别提高13.6%~29.6%,与相应剂量DTX 组相比抑瘤率分别提高33.5 % ~34.3 %,其中DDP+DTX 0.75 +7.5mg·kg^-1组与DDP及相应剂量DTX 组相比较有显著意义(P<0.01~0.001);DDP组及两药联合应用各剂量组使小鼠胸腺指数和脾指数明显低于对照组。结论: 低剂量DDP与DTX 联合使用加强了对肿瘤生长的抑制作用,与DDP组相比,联合应用引起的免疫器官的萎缩与DDP组无差别。     

河鲀Ⅰ型胶原蛋白提取物防治环磷酰胺、顺铂或阿糖胞苷诱发小鼠骨髓抑制的研究

目的:观察河Ⅰ 型胶原蛋白提取物(Pufferfish type Ⅰ collagen extract, PTICE) 对环磷酰胺(CTX) 、顺铂(DDP) 或阿糖胞苷(Ara-c) 诱发的小鼠骨髓抑制的影响。方法:分别用CTX 、DDP 、Arac腹腔注射(i.p.) 诱发小鼠骨髓抑制、免疫抑制等毒副反应, PTICE 灌胃(i.g.) 预防治疗, 观察小鼠的一般状况, 测定外周血细胞分类、脾脏指数和骨髓DNA 含量。结果:PTICE 可改善应用上述化疗药物小鼠的一般状况, 保护小鼠毛发, 升高外周血中的白细胞、血小板、中性粒细胞、淋巴细胞数,增加脾脏指数和骨髓DNA 含量;PTICE 显著降低DDP 导致的小鼠死亡率。结论:PTICE 可降低化疗药物引起的小鼠骨髓抑制等毒副作用。     

丁磺氨酸增强氮芥和环磷酰胺对肿瘤细胞的杀伤作用

目的 的研究谷胱甘肽合成抑制剂丁磺氨酸(BSO)对氮芥及环磷酰胺体内外细胞毒作用的影响。方法 利用改良MTT 法及瘤体称重法检测化疗药对肿瘤细胞生长的抑制作用。结果 在体外BSO明显降低人HL-60白血病细胞中谷胱甘肽的含量, 并显著增强氮芥的细胞毒作用, 剂量修饰因子为9.19 。在体内BSO能增强环磷酰胺对小鼠Hepa A肝癌及Lewis肺癌的生长抑制作用, 抑制率分别由26.1%升至51.5%, 和由22.6%升至32.3%。结论 BSO 可增强氮芥和环磷酰胺对肿瘤细胞的体内外杀伤作用。     

Processed Aloe vera Gel Ameliorates Cyclophosphamide-Induced Immunotoxicity

The effects of processed Aloe vera gel (PAG) on cyclophosphamide (CP)-induced immunotoxicity were examined in mice. Intraperitoneal injection of CP significantly reduced the total number of lymphocytes and erythrocytes in the blood. Oral administration of PAG quickly restored CP-induced lymphopenia and erythropenia in a dose-dependent manner. The reversal of CP-induced hematotoxicity by PAG was mediated by the functional preservation of Peyer’s patch cells. Peyer’s patch cells isolated from CP-treated mice, which were administered PAG, produced higher levels of T helper 1 cytokines and colony-stimulating factors (CSF) in response to concanavalin A stimulation as compared with those isolated from CP-treated control mice. PAG-derived polysaccharides directly activated Peyer’s patch cells isolated from normal mice to produce cytokines including interleukin (IL)-6, IL-12, interferon-γ, granulocyte-CSF, and granulocyte-macrophage-CSF. The cytokines produced by polysaccharide-stimulated Peyer’s patch cells had potent proliferation-inducing activity on mouse bone marrow cells. In addition, oral administration of PAG restored IgA secretion in the intestine after CP treatment. These results indicated that PAG could be an effective immunomodulator and that it could prevent CP-induced immunotoxic side effects.     

Preparation and release profiles of cyclophosphamide from segmented polyurethanes

Supermolecular structure of drug delivery system on the basis of segmented polyurethane (SPU) has been determined to control the release of anticancer drug, cyclophosphamide (CPh). It has been established that the phase separation in SPU is essentially intensified by means of both the increase of molecular weight for SPU's soft segments and CPh incorporation in the monolithic systems of polyethylene glycol‐based polyurethane. Infrared and proton NMR data indicate that CPh is hydrogenicly associated with a urethane group of hard segments. It has been determined that the drug‐concentrated domains of hard segments are microheterogeneously dispersed in the amorphous soft segments. These results indicate that a supermolecular structure design of SPU allows for control of the CPh release from the polymer matrix. Medical‐biological tests of the prepared polyurethane device have shown reduced toxic action of the cytostatic drug compared with injections. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 75: 35–43, 2000