摘要
目的分析EZH2在慢性髓细胞性白血病大鼠中调控机制。方法选取SPF级Wistar雌性大鼠60只,制备慢性髓细胞性白血病(CML)模型,shEZH2(EZH2敲低)组和shEZH2+IM组大鼠行EZH2敲低实验,移植第2天,IM组、shEZH2+IM组灌胃剂量为100 mg/kg的伊马替尼(IM)药液,shEZH2组、溶剂组灌胃20%磺丁基-β-环糊精(Captisol)。末次给药后解剖观察各组大鼠脾脏肿大和结节情况,检测大鼠髓系细胞与白血病细胞比例、白血病祖细胞比例、白血病干细胞比例情况和骨髓内mTOR、Akt及PI3K蛋白表达量。结果 shEZH2组及shEZH2+IM组大鼠脾脏和骨髓内髓系细胞与白血病细胞比例较溶剂组显著降低,差异有统计学意义(P<0.05);shEZH2组及shEZH2+IM组大鼠脾脏和骨髓内中粒细胞巨噬细胞祖细胞、共同淋巴系祖细胞比例较溶剂组显著降低,差异有统计学意义(P<0.05);shEZH2组及shEZH2+IM组大鼠骨髓内mTOR、Akt及PI3K蛋白表达较溶剂组升高,差异有统计学意义(P<0.05)。结论敲低CML大鼠移植细胞内EZH2,可有效降低骨髓和脾脏内CML细胞不同亚群细胞比例,其作用机制可能和上调PI3K/AKT/mTOR信号通路内各蛋白表达有关。
Objective To analyze the regulation mechanism of EZH2 in chronic myeloid leukemia rats. Methods 60 SPF-derived Wistar female rats were selected to prepare chronic myeloid leukemia(CML) model. The shEZH2(EZH2 knockdown) group and the shEZH2+IM group were subjected to EZH2 knockdown test. On the second day of transplantation, IM group and shEZH2+IM group received 100 mg/kg imatinib(IM) solution, shEZH2 group and solvent group received 20% sulfobutyl-β-cyclodextrin(Captisol). After the last administration, the spleen enlargement and nodules of the rats in each group were observed by anatomy. The ratio of myeloid cells to leukemia cells, the proportion of leukemia progenitor cells, the proportion of leukemia stem cells and the expression of mTOR, Akt and PI3 K protein in bone marrow were detected. Results The ratio of spleen and bone marrow mesangial cells to leukemia cells in shEZH2 group and shEZH2+IM group was significantly lower than that in the solvent group(P<0.05). The proportion of neutrophil macrophage progenitor cells and common lymphoid progenitor cells in spleen and bone marrow of shEZH2 group and shEZH2+IM group was significantly lower than that in the solvent group(P<0.05). The protein expression of mTOR, Akt and PI3 K proteins in rat bone marrow of shEZH2 group and shEZH2 +IM group was higher than that in the solvent group, and the difference was statistically significant(P<0.05). Conclusion The knockdown of EZH2 in the transplanted cells of CML rats can effectively reduce the proportion of different subpopulations of CML cells in bone marrow and spleen. The mechanism may be related to the up-regulation of the expression of various proteins in PI3 K/AKT/mTOR signaling pathway.
作者
章宝繁
吴圣豪
ZHANG Baofan;WU Shenghao(Department of Chemotherapy,Wenzhou Central Hospital in Zhejiang Province,Wenzhou 325000,China)
出处
《中国现代医生》
2019年第31期34-37,共4页
China Modern Doctor
基金
浙江省基础公益研究计划项目（LGD19H080001）
