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本研究旨在利用大剂量人重组红细胞生长素(rhEPO)诱导骨髓纤维化(M F)小鼠模型。60只昆明小鼠分为正常对照和EPO诱导组,分别用生理盐水和rhEPO进行腹腔注射,在实验第6、30、60、90、120和150天每组分别处死5只鼠。用细胞分析仪测定外周血白细胞数、血红蛋白(Hb)水平、红细胞平均体积(MCV)、红细胞分布宽度(RDW)和血小板量;用流式细胞术检测骨髓CD34阳性细胞率,称重肝、脾,计算肝、脾系数,利用HE和网状纤维染色分析肝、脾、股骨病理变化;应用高清CT测定股骨皮质厚度、髓腔直径和腰椎密度。结果表明,与正常对照组相比,EPO组各阶段白细胞轻度增高,但无统计学差异(p>0.05);Hb和RDW在第6和30天增高显著(p<0.05);MCV在第6天增高显著(p<0.05);各阶段血小板数降低,在第120和150天差异显著(p<0.05)。EPO组第60天肝肿大明显,肝系数差异显著(p<0.05);各阶段脾肿大,脾系数差异显著(p<0.05)。EPO组各阶段骨髓CD43阳性细胞率显著增高(p<0.05),第150天CT显示股骨皮质增厚,髓腔变窄,密度不均,腰椎密度增高。病理检查显示,EPO组小鼠肝脂肪化和空泡化,脾脏巨核细胞增多,股骨硬化和骨髓纤维组织增多。结论:大剂量rhEPO可诱导小鼠出现M F特有临床和病理特点。本研究对建立新的M F模型和病理研究有重要意义。
The aim of this study was to induce myelofibrosis (M F) mouse model by using large doses of human recombinant erythropoietin (rhEPO). Sixty Kunming mice were divided into normal control group and EPO induction group, which were injected intraperitoneally with normal saline and rhEPO respectively. Five rats were killed in each group on the 6th, 30th, 60th, 90th, 120th and 150th day. Peripheral white blood cell count, hemoglobin (Hb) level, mean corpuscular volume (MCV), distribution width of red blood cells (RDW) and platelet volume were measured by cell analyzer; the rate of bone marrow CD34 positive cells was measured by flow cytometry; The liver and spleen indexes were calculated. The pathological changes of liver, spleen and femur were analyzed by HE staining and reticular fiber staining. The thickness of femoral cortex, the diameter of medullary cavity and the density of lumbar spine were measured by high-resolution CT. The results showed that compared with the normal control group, the number of leukocytes in each stage of EPO increased slightly (p> 0.05), the levels of Hb and RDW increased significantly on the 6th and 30th days (p <0.05) (P <0.05). The number of platelets in each stage decreased significantly at day 120 and 150 (p <0.05). In the EPO group, hepatomegaly was obvious on the 60th day, and the difference of the hepatic coefficient was significant (p <0.05). The splenomegaly and spleen coefficient of each stage were significantly different (p <0.05). In the EPO group, the percentage of CD43 positive cells in each stage was significantly increased (p <0.05). On the 150th day, CT showed thickened femoral cortex, narrowed medullary cavity, uneven density and lumbar spine density. Pathological examination showed that hepatic steatosis and vacuolization, spleen megakaryocytosis, femoral sclerosis and myelofibrosis were increased in EPO mice. Conclusion: High dose rhEPO can induce mouse M F specific clinical and pathological features. This study is of great importance to establish a new M F model and pathology.