【摘要】 目的:探讨当归多糖(ASP)与阿糖胞苷(Ara-C)联合注射对移植性人白血病模型小鼠脾脏结构与功能的影响及其相关机制。方法:每只小鼠尾静脉移植2×107个K562细胞建立移植性人白血病NOD/SCID小鼠模型,模型建立后随机分为模型组和当归多糖组、阿糖胞苷组、当归多糖+阿糖胞苷组。从移植K562细胞第31d开始腹腔分别注射当归多糖(200 mg/kg、阿糖胞苷(2.5mg/kg)和当归多糖(200 mg/kg)+阿糖胞苷(2.5 mg/kg),共14d,模型组注射等时等量的生理盐水。药物注射完成第2d,取眼球血检测外周血白细胞总数与分类计数,取股骨测定每只股骨有核细胞(BMMCs)数,取脾脏测定脾指数并将新鲜小块脾制作成10μm冷冻切片,HE和TUNEL染色观察脾脏病理形态学与细胞凋亡情况。取0.04 g脾脏制备10%的组织匀浆,提取各组上清液并检测抗氧化酶谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD),氧化产物谷胱甘肽(GSH)、丙二醛(MDA)的蛋白浓度与炎症因子IL-1β、IL-6水平。结果:与模型组比较,无论是当归多糖、阿糖胞苷单独注射或当归多糖和阿糖胞苷联合用药均能有效降低外周血白细胞总数,降低中性粒细胞百分率,提高淋巴细胞百分率;降低股骨BMMCs数;减少脾指数;白血病细胞对脾浸润减少且凋亡率增加;脾脏抗氧化能力下降得以抑制,表现为GSH-Px与SOD活性升高,氧化产物GSH与MDA降低;炎症因子IL-1β、IL-6水平降低,且联合用药组效果更为明显。结论:当归多糖与阿糖胞苷能减少白血病细胞在脾脏内聚集,促进白血病细胞衰老凋亡,降低白血病细胞对脾结构与功能损伤,减轻脾脏炎症反应,提高脾组织抗氧化能力。更多还原

【Abstract】 Objective: To investigate the splenic structure and function of human leukemia model NOD /SCID mouse treated with combining injection of Angelica sinensis polysaccharides( ASP) and cytosine arabinoside( Ara-C) and its related mechanism. Methods: The human leukemia mouse model was established by transplanting 2 × 107K562 cells into the caudal vein of NOD /SCID mouse. They model mouse were randomly divided into 4 groups,such as ASP,Ara-C,ASP + Ara-C and control. After 31 days of transplanting K562 cells,leukemia model mouse were respectively injected with ASP( 200 mg /kgod),Ara-C( 2. 5mg /kgod) or ASP( 200 mg /kgod) + Ara-C( 2. 5mg /kgod) by way of peritoneal for 14 days. All control mouse were given saline in the same volume and time. After 2 days of finishing injections,the number and classification of peripheral white blood cells,femur bone marrow monneucleared cells( BMMCs) were counted,the splenic index was calculated,the 10μm fresh spleen frozen sections were perpareed and stained with HE and TUNEL to observe splenic pathological structure and cell apoptosis. By preparation and collection of the supernatants of splenic tissue homogenates,the levels of GSH-Px,GSH,SOD,MDA and pro-inflammatory cytokines IL-1β,IL-6 in supernatants were for assayed by chemical colorimetric analysis and ELISA. Results: The results indicated that after injected leukemia mouse model with ASP or ASP + Ara-C,the number of white blood cells and percentages of neutrophil were reduced and lymphocyte was enhanced significantly in the peripheral blood,the number of BMMCs and splenic index were decreased,the leukemia cells infiltrated into the spleen were reduced and apoptotic positive cell were increased remarkably,the antioxidant enzyme glutathione peroxidase( GSH-Px) and superoxide dismutase( SOD) were significantly increased and the oxidation products of glutathione( GSH) and malonaldehyde( MDA) were raised,the inflammatory cytokines level of IL-1βand IL-6 were decreased significantly. The combined injection of Ara-C with ASP showed much better effects than other groups. Conclusion: Combining Ara-C with ASP may reduce leukemia cells accumulate in the spleen,promote senescence or apoptosis of leukemia cells,decrease the splenic structure and function damage from leukemia cells and the levels of inflammatory factors,improve antioxidant capacity of the splenic tissue.更多还原