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目的从病理学角度研究酒石酸长春瑞滨(NVB)对大鼠免疫和造血系统的长期毒性作用。方法 48只SD大鼠,雌雄各半,随机分为正常对照组和NVB 5.0,10.0和20.0 mg·m-2组。NVB静脉滴注给药,第1和第8天各给药1次,21 d为1个周期,共给药4个周期。末次给药后14 d腹主动脉取血,用ADVIA2120血液分析仪检测白细胞(WBC)、中性粒细胞(Neut)、淋巴细胞(Lym)和红细胞(RBC)数及网织红细胞千分比值(RET‰);剖取胸腺、胸骨骨髓、脾和肠系膜淋巴结进行组织病理学检查;精密称取胸腺和脾质量,计算脏器系数;取出股骨骨髓,进行骨髓涂片分类计数。结果与正常对照组比较,NVB 5.0,10.0和20.0 mg·m-2组雌雄大鼠外周血中WBC,Neut,Lym和RBC数及RET‰均降低(P<0.05,P<0.01),其中雄性大鼠正常对照组Neut为(2.35±0.56)×109L-1,NVB各组分别降低为(1.66±0.44),(0.67±0.22)和(0.20±0.02)×109L-1;雌性大鼠正常对照组Neut为(1.26±0.27)×109L-1,NVB各组分别降低为(1.14±0.56),(0.47±0.13)和(0.21±0.08)×109L-1。骨髓涂片分类计数结果显示,粒系细胞比例降低(P<0.05,P<0.01),其中雄性大鼠正常对照组粒系百分比为(42.7±6.1)%,NVB各组分别降低为(28.8±5.3)%,(22.0±3.2)%和(18.9±3.9)%;雌性大鼠正常对照组粒系百分比为(35.4±3.0)%,NVB各组分别降低为(31.2±4.7)%,(22.9±6.7)%和(20.8±4.2)%。胸腺系数降低(P<0.05,P<0.01),其中雄性大鼠正常对照组为0.36±0.04,NVB各组分别降低为0.31±0.06,0.18±0.03和0.08±0.01;雌性大鼠正常对照组为0.29±0.06,NVB各组分别降低为0.25±0.06,0.19±0.06和0.07±0.01。组织病理学检查结果显示,NVB 5.0,10.0和20.0 mg·m-2可致雌雄大鼠不同程度的胸腺萎缩和骨髓造血抑制,NVB各剂量组亦可见不同程度的脾代偿性髓外造血细胞增多,肠系膜淋巴结均未见明显病理改变。结论 NVB对SD大鼠免疫和造血系统具有毒性作用,表现为胸腺萎缩和骨髓造血抑制。
Objective To study the long-term toxicity of vinorelbine tartrate (NVB) to the immune and hematopoietic system in rats from the pathological point of view. Methods 48 SD rats, male and female, were randomly divided into normal control group and NVB 5.0, 10.0 and 20.0 mg · m-2 groups. NVB intravenous administration, on the first and eighth days of each administration 1, 21 d for a cycle, a total of 4 cycles. Blood samples were taken from the abdominal aorta on the 14th day after the last administration, and the numbers of WBC, Neut, Lym, RBC and RET were measured by ADVIA2120 hematology analyzer (RET ‰). The thymus, sternum, spleen and mesenteric lymph nodes were dissected for histopathological examination. The thymus and spleen mass were accurately weighed and the organ coefficients were calculated. The femur bone marrow was removed and the bone marrow smears were counted. Results Compared with the normal control group, the WBC, Neut, Lym and RBC numbers and RET ‰ of NVB in 5.0, 10.0 and 20.0 mg · m-2 groups were significantly decreased (P <0.05, P <0.01) Neut was 2.35 ± 0.56 × 109L-1 in normal control group and 1.66 ± 0.44, 0.67 ± 0.22 and 0.20 ± 0.02 × 109L-1 in NVB group respectively. The normal control group Neut was (1.26 ± 0.27) × 109L-1 in the group and decreased to (1.14 ± 0.56), (0.47 ± 0.13) and (0.21 ± 0.08) × 109L-1 in NVB group. The number of granulosa cells was decreased (P <0.05, P <0.01). The percentages of granulocytes in the normal control group were (42.7 ± 6.1)%, and those in the NVB group were decreased to (28.8 ± 5.3%, 22.0 ± 3.2% and 18.9 ± 3.9%, respectively. The percentage of granulocyte in the normal control group was (35.4 ± 3.0)% in the female rats and (31.2 ± 4.7)% in the NVB groups ± 6.7% and (20.8 ± 4.2)% respectively. (P <0.05, P <0.01). The normal control group was 0.36 ± 0.04 in male rats and 0.31 ± 0.06,0.18 ± 0.03 and 0.08 ± 0.01 in NVB groups. The normal control group was 0.29 ± 0.06, NVB decreased to 0.25 ± 0.06, 0.19 ± 0.06 and 0.07 ± 0.01 respectively. Histopathological examination showed that NVB at 5.0, 10.0 and 20.0 mg · m-2 induced thymus atrophy and hematopoietic suppression in both male and female rats, and all the NVB doses also showed varying degrees of compensated extramedullary hematopoietic cells Increased, no significant pathological changes in mesenteric lymph nodes. Conclusion NVB has a toxic effect on the immune and hematopoietic system of SD rats, showing thymus atrophy and inhibition of bone marrow hematopoiesis.