血小板因子4对环磷酰胺诱导化学损伤小鼠骨髓细胞的保护作用_医学论文.docVIP

血小板因子4对环磷酰胺诱导化学损伤小鼠骨髓细胞的保护作用_医学论文 血小板因子4对环磷酰胺诱导化学损伤小鼠骨髓细胞的保护作用_医学论文 作者：宋俊玲　杨岚　田琼　袁诚君 【关键词】 血小板因子 关键词: 血小板因子环磷酰胺造血干细胞 摘 要:目的 探讨血小板因子4（PF4）对环磷酰胺（CTX）诱导化学损伤小鼠骨髓的保护作用及机制. 方法 环磷酰胺200mg#12539kg-1 ，腹腔一次性注射，造成药物损伤模型.给CTX前给予PF4预处理，给药后动态观察小鼠外周血白细胞数的变化，并于第5和第8日，分别用流式细胞仪（FCM）测定骨髓有核细胞DNA的含量及细胞周期变化. 结果 注射CTX后4d，外周血白细胞降至最低点，然后逐渐回升，但PF4处理组与单独CTX处理组比较无差异（Pgt0.05）.第5日PF4处理组的骨髓有核细胞中，G0 /G1 期细胞的百分率较CTX组明显提高，细胞的坏死、凋亡率下降（0.01），而与PBS对照组基本相同（Pgt0.05）.第8日PF4处理组的骨髓有核细胞数较单独CTX处理组增加明显（0.01）. 结论 PF4对CTX损伤的小鼠骨髓细胞有保护作用，可作为肿瘤患者使用烷化剂化疗时的骨髓防护剂. 　　Keywords:platelet factorcyclophosphamidehematopoietic stem cell Abstract:AIM To provide evidence for studying the chemo-protective effect of PF4and its machanism on murine hematopoietic cells treated with CTX.METHODS The mice were intraperitoneal（IP）injected with PF4（40μg#12539kg-1 ）twice at6h intervals.20h after the second injection they were given one injection of CTX（200mg#12539kg-1 ）to make the models of chemical lesions.Then the numbers of their peripheral WBC were observed.5d，8d later the DNA contents in bone marrow cells were detected by flow cyteme-try（FCM）.RESULTS There were no difference between the peripheral WBC counts of PF4treatment groups and the one of CTX groups（Pgt0.05）.On day5，bone marrow cells in G0 /G1 phase in PF4treatment groups were significantly higher than that in CTX groups，and the necrotic and apop-totic percentage were significantly lower，but there was no difference between the PF4groups and the PBS control groups.On day8after CTX treatment，bone marrow cellu-larity in PF4treatment groups were significantly higher than that in CTX groups.CONCLUSION PF4can protect murine bone marrow from the cytotoxic effects of CTX.PF4should be a potent protective agent during chemotherapy. 　　0 引言 　　骨髓造血系统是对化疗非常敏感的组织，在造血系统恶性肿瘤的治疗过程中，常因骨髓造血抑制而限制化疗药物的剂量，直接影响肿瘤的治疗效果.环磷酰胺（CTX）是肿瘤化疗中最常用的烷化剂，但其对正常骨髓细胞也有很强的抑制作用.此外，作为免疫抑制剂的化疗药物，CTX还是干细胞移植前预处理最常用的药物之一.已有研究表明，血小板因子4（PF4）对5-FU处理的小鼠骨髓有明显的保护作用［1］ .但Han等［2］ 体外实验证明，PF4对HL-60，HEL，SMMC7721及MKN-4