不同剂量环孢菌素A制备免疫缺陷小鼠模型的研究

Study on Different Doses of Cyclosporin A for Preparing Immunodeficiency Mice Models

目的研究不同剂量环孢菌素A(CsA)对小鼠免疫功能的影响,为细胞免疫缺陷型动物模型的建立奠定基础。方法实验设CsA高、中、低剂量组,溶液对照组和正常对照组。CsA高、中、低剂量组分别经腹腔注射CsA40、25、10mg/(kg·d),溶液对照组给予等容积的稀释液,正常对照组给予等容积生理盐水,隔天1次,共注射3次。观察以下指标:(1)CD4+T和CD8+T细胞亚群百分率;(2)小鼠脾脏、胸腺质量指数和病理变化;(3)小鼠肺组织的病理变化及小鼠死亡率。结果与正常对照组和溶液对照组比较:(1)高、中剂量CsA组CD4+T细胞亚群百分率明显下降(P<0.05或P<0.01),高剂量组CD8+T细胞亚群百分率明显升高(P<0.05);(2)CsA高、中剂量组胸腺指数明显下降(P<0.01),胸腺萎缩、脂肪变性、中间有淋巴小结样结构,脾脏指数各组间前后均无明显改变;高、中、低剂量组脾脏均有代偿性的白髓增大、脾小体增大、巨噬细胞增多;(3)高、中、低剂量CsA肺脏有局灶性炎症改变、间质增生、肺泡纤维度增生;高剂量组的小鼠死亡率显著升高,达60%。结论腹腔注射高、中剂量的CsA均可成功建立免疫缺陷型动物模型,但从效率和经济性考虑,中剂量CsA更适合用于模型的建立。

Objective To study different doses of cyclosporin A （CSA） on the effect of immune function in mice and to lay the foundation for cellular immune deficient animal model. Methods The experiment is divided into high dose group, middle dose group, and low dose group, which were intraperitoneal injected with CSA： 40 mg/（kg.d）, 25 mg/（kg.d） and 10 mg/（kg.d）, respectively. We also set solution control group which were given the same dose of diluent, and normal control group which were given equal saline, injecting one times every other day for total three times. The following indicators were observed： （1） The percentage of CD4CF and CDSCF lymphocyte subsets; （2） The weight index and pathological changes of the spleen and thymus; （3） Pathological changes of the lung and mortality rate in mice. Results Compared with normal control group and solution control： （1） high and middle dose group of the percentage of CD4~T cells decreased apparently （P〈O.O5/P〈O.O1）. The percentage of CD8CF cells increased significantly only in the high dose group （P〈0.05）. （2） High and middle dose group of the weight index of thymus decreased apparently （P〈0.05）, thymus atrophy associated with fatty degeneration, lymphoid nodule sample structure in the middle; spleen white medullary and splenic corpuscle in the high, middle and low dose group enlarged and macrophages increased; （3） The lungs in the high, middle and low dose groups had focal inflammation, pulmonary interstitial hyperplasia and alveolar fiber hyperplasia; The mortality in high dose group of significantly increased （P〈 0.05）. Conclusion The immune deficiency mice models could be successfully established by intraperitoneal injection of high or middle dose CSA. While considering from efficiency and economy, middle dose CSA is more suitable for building models.