尾静脉注射BA/F3-JAK2V617F细胞构建BALB/c小鼠真性红细胞增多症模型  

Construction of polycythemia vera BALB/c mouse model by tail vein injection of BA/F3-JAK2V617F cells

作　　者：石镇港 夏伟 刘学武 冯璐瑶 冯超 赵丞 姜德建 信红亚[3] SHI Zhen-gang;XIA Wei;LIU Xue-wu;FENG Lu-yao;FENG Chao;ZHAO Cheng;JIANG De-jian;XIN Hong-ya(National Key Laboratory Cultivation Base for Hunan Traditional Chinese Medicine Powder and Innovative Medicine Co-established by Province and Ministry,Changsha 410208;Hunan Center of Drug Safety Evaluation and Research,Hunan Key Laboratory of Pharmacodynamics and Safety Evaluation of New Drugs,Changsha 410331;Department of Hematology,Xiangya Hospital,Central South University,Changsha 410008)

机构地区：[1]湖南省中药粉体与创新药物省部共建国家重点实验室培育基地,长沙410208 [2]湖南省药物安全评价研究中心,新药药效与安全评价湖南省重点实验室,长沙410331 [3]中南大学湘雅医院血液科,长沙410008

出　　处：《中南药学》2021年第4期637-641,共5页Central South Pharmacy

基　　金：湖南省重点领域研发计划项目人源化小鼠质量保障关键技术研究与应用(No.2020DK2003)。

摘　　要：目的应用BA/F3-JAK2V617F细胞构建BALB/c小鼠真性红细胞增多症模型。方法40只雌性BALB/c小鼠,随机分为空白对照组、低剂量组、中剂量组、高剂量组、芦可替尼组。接种前各组小鼠均接受1.0 Gay的全身辐照,24 h内分别接种不同浓度的BA/F3-JAK2V617F、BA/F3-Blank细胞,并给予相应药物28 d。末次给药后,采血、取材进行血液学检测、骨髓涂片、组织病理学检测。结果与空白对照组比较,中、高剂量组外周血红细胞数(RBC)、血红蛋白(HGB)、红细胞比容(HCT)升高,骨髓中粒细胞系、粒红比减少,红细胞系增加,体重明显下降,脾脏重量、脾指数明显增大;低剂量组HGB、脾指数显著升高,粒细胞系、粒红比减少。与高剂量组比较,芦可替尼组RBC、HGB、HCT、骨髓中红细胞系、脾脏重量、脾指数均明显降低,体重、骨髓中粒细胞系、粒红比均明显升高。空白对照组病理检测无明显变化;低剂量组胸骨骨髓造血活跃;中剂量组脾脏髓外造血,胸骨、股骨造血活跃;高剂量组脾脏髓外造血,腰椎、股骨、胸骨骨髓造血活跃;芦可替尼组胸骨骨髓造血活跃。结论BALB/c小鼠经1.0 Gay剂量的全身辐照后,尾静脉注射BA/F3-JAK2V617F 1.0×106~1.6×10^(6)个细胞可成功构建真性红细胞增多症动物模型,符合真性红细胞增多症的生物学特点。Objective To construct BALB/c mouse polycythemia vera model with BA/F3-JAK2V617F cells.Methods Totally 40 female BALB/c mice were randomly divided into a blank control group,a low dose group,a middle dose group,a high dose group and a ruxolitinib group.Before the inoculation,the mice in each group were irradiated by 1.0 Gay.Different concentrations of BA/F3-JAK2V617F and BA/F3-Blank cells were inoculated within 24 h,and corresponding drugs were given for 28 days.After the last administration,the blood samples were collected for hematological examination,bone marrow smear and histopathological examination.Results Compared with the blank control group,the red blood cell number(RBC),hemoglobin(HGB)and hematocrit(HCT)in the middle and high dose groups increased;the granulocyte series and granulocyte-red ratio in the bone marrow decreased,the erythrocyte line increased,the body weight decreased obviously,and the spleen weight and spleen index increased.In the low dose group,HGB and spleen index increased significantly,while granulocyte line and granulocyte-red ratio decreased.Compared with the high dose group,RBC,HGB,HCT,and erythrocyte series in the bone marrow,spleen weight and spleen index were significantly decreased,while the body weight,granulocyte series and granulocyte-red ratio in bone marrow were significantly increased in the ruxolitinib group.There was no significant change in the blank control group.The low dose group showed active sternal bone marrow hematopoiesis;the middle dose group showed active spleen extramedullary hematopoiesis,sternum and femur hematopoiesis;the high dose group showed active spleen extramedullary hematopoiesis and lumbar spine,femur and sternal bone marrow hematopoiesis.Active hematopoiesis of sternal bone marrow was found in the ruxolitinib group.Conclusion The mouse model of polycythemia is successfully established in BALB/c mice by tail vein injection of 1.0×10^(6)to 1.6×10^(6)BA/F3-JAK2V617F cells after whole body irradiation at 1.0 Gay,which accords with the biological cha

关 键 词：真性红细胞增多症 JAK2V617F 动物模型 BA/F3细胞 

分 类 号：R96[医药卫生—药理学]