摘要
目的比较4种不同剂量和不同方式给予环磷酰胺诱导正常小鼠免疫抑制的4种方法,选择合适的免疫抑制动物模型以评价受试物的免疫毒性。方法选择雌性BALB/c小鼠,设1个对照组(每日灌胃蒸馏水)和4个环磷酰胺组(灌胃组每天40 mg/kg BW;腹腔注射1组每天40 mg/kg BW;腹腔注射2组,先连续注射3 d,后每周注射一次,注射剂量为80 mg/kg BW;腹腔注射3组,试验结束前24 h一次性注射200 mg/kg BW),试验周期为30 d。观察不同剂量及不同途径给予环磷酰胺后对小鼠免疫病理学、体液免疫、细胞免疫、非特异性免疫等各项免疫指标的影响。结果 4个环磷酰胺组的小鼠免疫器官重量、外周血白细胞计数及其淋巴细胞百分比、血清免疫球蛋白水平、外周血B淋巴细胞百分比、脾空斑形成细胞数、24 h小鼠足跖厚度变化、脾T淋巴细胞和B淋巴细胞增殖能力较对照组均有不同程度下降,全血中性粒细胞百分比均高于对照组。环磷酰胺灌胃组和注射1组可刺激全血NK细胞百分比较对照组明显升高,而注射2组和3组的Th细胞百分比和CD4+/CD8+值均高于对照组,其差异分别具有统计学意义(P<0.05)。此外,环磷酰胺灌胃组和注射1组还可引起动物体重下降、肝脏相对重量降低、血清谷丙转氨酶、血糖、甘油三酯的改变。对于试验所测定的大部分指标,注射2组和注射3组之间比较差异无统计学意义(P>0.05)。结论环磷酰胺的4种给予方式均可诱导动物免疫抑制,但于试验结束前24 h一次性腹腔注射200 mg/kg BW环磷酰胺为最合适的免疫抑制动物模型造模方法。
Objective To compare four methods for developing immune-suppressed mouse models induced by cyclophos- phamide （CP） with different doses and ways, and choose the appropriate animal model of immunosuppression to evaluate the immunotoxicity of a substance. Methods The female BALB/c mice were assigned to five groups： the control group with distilled water daily garage; CP gavage group with 40 mg/kg BW/d by garage; CP ip-I group with 40 mg/kg BW/d by intraperitoneally injection （ip） ; CP ip-2 group with 80 mg/kg BW/d in the first three days by ip and once a week in the following period; CP ip-3 group with 200 mg/kg BW 24 h before the end point by ip. The study lasted for 30 days. Results The immune organ weights, the number of leucocyte and the percentage of lymphocytes in peripheral blood, IgA and IgG levels in serum, the percentage of B cells in peripheral blood, the plaque forming ceils in spleen, 24 h footpad thickness change, LPS- and ConA-indueed splenocyte proliferation in four cyclophosphamide groups were significantly lower than those in control group （ P 〈 O. 05）. The percentages of neutrophils in peripheral blood in four eyclophosphamide groups were significantly higher than those in control group （P 〈 0. 05 ）. However, the percentage of NK cells in peripheral blood in CP gavage group and CP ip-1 group were significantly higher than that in control group, and the percentage of Th cells and the ratio of CD4＋ to CD8 ＋ in CP ip-2 group and CP ip-3 group were higher than those in control group （ P 〈 0.05 ）. In addition, the body weight and liver relative weight in CP garage group and CP ip-1 group were lower than those in control group, the levels of alanine aminotransferase, glucose and triglyeeride changed significantly （ P 〈0. 05 ）. There was no significant difference between CP ip-2 group and CP ip-3 group except the body weight and haematology parameters such as mean corpuscular hemoglobin concentration and red blood cell distribution width （ P 〉 0.05 ）. Conclusion The four ways of CP administration could induce immunosuppression in BALB/c mice, however the appropriate animal model of immunosuppression may be established by intraperitoneal injection of 200 mg/kg BW CP 24 h before the end point.
出处
《中国食品卫生杂志》
北大核心
2013年第3期218-225,共8页
Chinese Journal of Food Hygiene
基金
社会公益项目(200903054-06)
转基因重大专项(2012BAK01B00)
关键词
环磷酰胺
免疫抑制
免疫病理学
体液免疫
细胞免疫
非特异性免疫
小鼠
Cyclophosphamide
immunosuppression
immunopathology
humoral immunity
cell-mediated immunity
non-specific immunity
mice
