CYCLOPHOSPHAMIDE-INDUCED IMMUNOLOGIC AND MORPHO-FUNCTIONAL ALTERATIONS OF THE SPLEEN IN EXPERIMENTAL MODELS WITH EMPHASIS IN CHINCHILLA RABBITS

Cyclophosphamide is an alkylating agent widely used in oncology, autoimmune diseases, and experimental immunosuppression models. Despite its therapeutic efficacy, cyclophosphamide induces profound immunotoxic and morpho-functional alterations in lymphoid organs, particularly the spleen. This literature review critically analyzes experimental data from the last decade, with special emphasis on splenic injury induced by cyclophosphamide in Chinchilla rabbits and other animal models. Experimentally, cyclophosphamide undergoes hepatic bioactivation, leading to oxidative stress, mitochondrial dysfunction, and activation of intrinsic apoptotic pathways. These molecular processes result in selective lymphocyte depletion, alterations in cytokine profiles, and disruption of splenic microarchitecture. From an immunological perspective, cyclophosphamide suppresses T- and B-cell proliferation, reduces the CD4⁺/CD8⁺ ratio, weakens the humoral immune response, and alters macrophage and dendritic cell function. Morphologically and functionally, white pulp atrophy, regression of germinal centers, reduction of the marginal zone, sinusoidal dilation, vascular congestion, and increased apoptotic index are observed.环磷酰胺（Cyclophosphamide）是一类烷化剂，广泛应用于肿瘤学、自身免疫性疾病及实验性免疫抑制模型构建中。尽管具备治疗疗效，环磷酰胺可引发严重的免疫毒性及淋巴器官（尤其是脾脏）的形态与功能异常。本综述批判性分析了近十年的实验数据，重点聚焦环磷酰胺诱导的青紫蓝兔（Chinchilla rabbits）及其他动物模型的脾脏损伤。 实验研究显示，环磷酰胺需经肝脏生物活化（hepatic bioactivation），进而引发氧化应激、线粒体功能障碍及内源性凋亡通路激活。上述分子过程可导致淋巴细胞选择性耗竭、细胞因子谱改变及脾脏微结构破坏。 从免疫学视角来看，环磷酰胺可抑制T、B细胞增殖，降低CD4⁺/CD8⁺细胞比值，削弱体液免疫应答，并改变巨噬细胞与树突状细胞的功能。在形态与功能层面，可见白髓萎缩、生发中心消退、边缘区缩小、血窦扩张、血管充血及凋亡指数升高。