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Polysaccharides from the root of Angelica sinensis protect bone marrow and gastrointestinal tissues against the cytotoxicity of cyclophosphamide in mice

机译:当归根中的多糖可保护骨髓和胃肠道组织免受环磷酰胺对小鼠的细胞毒性作用

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Cyclophosphamide (CY) is a cytostatic agent that produces systemic toxicity especially on cells with high proliferative capacity, while polysaccharides from Angelica sinensis (AP) have been shown to increase the turnover of gastrointestinal mucosal and hemopoietic stem cells. It is not known whether AP has an effect on CY-induced cytotoxicity on bone marrow and gastrointestinal tract. In this study, we assessed the protective actions of AP on CY-induced leukopenia and proliferative arrest in the gastroduodenal mucosa in mice. Subcutaneous injection of CY (200 mg/kg) provoked dramatic decrease in white blood cell (WBC) count and number of blood vessels and proliferating cells in both the gastric and duodenal mucosae. Subcutaneous injection of AP significantly promoted the recovery from leukopenia and increased number of blood vessels and proliferating cells in both the gastric and duodenal tissues. Western blotting revealed that CY significantly down-regulated the protein expression of vascular endothelial growth factor (VEGF), c-Myc and ornithine decarboxylase (ODC) in gastric mucosae but had no effect on epidermal growth factor (EGF) expression. AP also reversed the dampening effect of CY on VEGF expression in the gastric mucosa. These data suggest that AP is a cytoprotective agent which can protect against the cytotoxicity of CY on hematopoietic and gastrointestinal tissues when the polysaccharide is co-administered with CY in cancer patients during treatment regimen.
机译:环磷酰胺(CY)是一种细胞抑制剂,特别是对具有高增殖能力的细胞产生全身毒性,而来自当归(AP)的多糖已显示可增加胃肠道粘膜和造血干细胞的周转率。尚不清楚AP是否对CY诱导的对骨髓和胃肠道的细胞毒性有影响。在这项研究中,我们评估了AP对CY引起的白细胞减少症和小鼠十二指肠粘膜增殖停滞的保护作用。 CY(200 mg / kg)的皮下注射引起胃黏膜和十二指肠黏膜中白细胞(WBC)的数量以及血管和增殖细胞的数量急剧减少。皮下注射AP显着促进白细胞减少症的恢复,并增加胃和十二指肠组织中血管和增殖细胞的数量。 Western印迹显示,CY显着下调了胃粘膜中血管内皮生长因子(VEGF),c-Myc和鸟氨酸脱羧酶(ODC)的蛋白表达,但对表皮生长因子(EGF)的表达没有影响。 AP还逆转了CY对胃黏膜中VEGF表达的抑制作用。这些数据表明,AP是一种细胞保护剂,当在治疗方案中将多糖与CY一起在癌症患者中联合使用时,可以保护CY对造血和胃肠组织的细胞毒性。

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