单次大剂量和多次小剂量环磷酰胺腹腔注射对小鼠免疫抑制模型的影响

试验旨在研究环磷酰胺不同剂量、不同给药次数对建立的小鼠免疫抑制模型免疫指标变化的影响。选择7周龄雄性昆明小鼠200只，随机均分为5组：对照组（生理盐水组，0 mg/g环磷酰胺）、环磷酰胺3次注射低剂量（0.04 mg/g）和高剂量（0.08 mg/g）组、环磷酰胺1次注射低剂量（0.10 mg/g）和高剂量（0.16 mg/g）组。3次注射组在试验第1天按照给定剂量腹腔注射环磷酰胺，连续注射3 d；对照组按照相同方法每天腹腔注射等体积生理盐水；1次注射组仅在试验第1天按照给定剂量腹腔注射环磷酰胺1次。试验期间每天对小鼠称重，在试验的第1、2、4、6、9、10、11天从各组分别选取8只小鼠采取尾静脉血检测血常规，并在试验的第1、4、6、9、11天从各组分别选取8只小鼠处死，测定股骨骨髓有核细胞、胸腺指数、脾脏指数等指标。结果表明，所有剂量环磷酰胺均可成功建立免疫抑制模型。抑制效果上，0.08 mg/g 3次注射对白细胞、骨髓有核细胞、体重增重、脾脏、胸腺的免疫抑制效果最好，0.16 mg/g 1次注射对红细胞免疫抑制效果最好。抑制周期上，环磷酰胺对白细胞、骨髓有核细胞、脾脏免疫抑制周期较短，对红细胞、胸腺的免疫抑制周期较长；1次注射均较3次注射更早且显著地出现白细胞免疫亢进，而脾脏免疫情况则刚好相反。综上，环磷酰胺不同给药剂量及给药次数对动物不同免疫部位的免疫状态及免疫抑制周期均会产生不同的影响。本研究可为药理试验中针对不同免疫指标进行观测时提供适当的检测剂量及检测时间参考。

Effects of Single High Dose and Multiple Low Dose Cyclophosphamide Abdominal Injection on Immunosuppressive Model in Mice

This study was designed to investigate and compare the immune effect of different immunosuppressive mice models which were injected with cyclophosphamide (CTX) at different doses and adminstration times. 200 male Kunming mice aged 7 weeks were randomly divided into 5 groups, including the control group (normal saline, 0 mg/g CTX), groups injected with low dose (0.04 mg/g) and high dose (0.08 mg/g) CTX for three times, groups injected with low dose (0.10 mg/g) and high dose (0.16 mg/g) CTX for once, respectively. The mice in 3 injections groups were given intraperitoneal CTX for 3 days and the mice in the control group were given equal volume normal saline in the same way. In the single injection groups, mice were given intraperitoneal CTX injection once only on the 1st day of the experiment. All the mice were weighted every day. On the 1st, 2nd, 4th, 6th, 9th, 10th and 11th day of the experiment, 8 mice of each group were selected to test tail vein blood. On the 1st, 4th, 6th, 9th and 11th day, 8 mice of each group were executed and measured nucleated cells of femur marrow, thymus indexes and spleen indexes. The results showed that the immunosuppressive model could be established successfully at all doses. In terms of inhibition effect, 0.08 mg/g three injections had the best immunosuppression effects on white blood cells, bone marrow nucleated cells, weight gain, spleen and thymus, and the 0.16 mg/g once injection had the best immunosuppression effect on red blood cells. In terms of inhibition cycle, the duration of inhibition was different in various immune sites, the inhibition cycle of cyclophosphamide were shorter on leukocytes, bone marrow nucleated cells and spleen than that on erythrocyte and thymus. The multiple injections groups showed earlier hyperimmunity in leukocyte than once injection groups, while the effect on spleen was just on the contrary. In conclusion, different doses and adminstraion times of CTX administration had different effects on the immune status and immunosuppression cycle of different immune sites. This study could provide appropriate detection dose and time reference for different immune indexes in pharmacological experiments.