湖南中医药大学学报2025，Vol.45Issue(4)：624-630,7.DOI:10.3969/j.issn.1674-070X.2025.04.006
白果内酯改善环磷酰胺所致小鼠免疫功能低下及其相关机制的研究
Amelioration of cyclophosphamide-induced immunocompromise in mice by bilobalide and its underlying mechanisms
摘要
Abstract
Objective To investigate the effects of bilobalide on cyclophosphamide(CTX)-induced immunocompromise in mice.Methods A total of 24 C57BL/6J mice were randomly divided into a normal group,a model group,a low-dose(10 mg/kg)bilobalide group,and a high-dose(20 mg/kg)bilobalide group,with six mice in each group.Except for the normal group,the other groups were intraperitoneally injected with CTX(50 mg/kg)on the 1st to 3rd day of the experiment to establish an immunocompromised mouse model.The mice in the normal and the model groups were gavaged with an equal volume of normal saline,while the bilobalide groups received low-or high-dose bilobalide by gavage once daily for 14 consecutive days.After the experiment,the body weight,thymus and spleen weight of mice were measured,and the thymus and spleen indices were calculated.The number of peripheral blood erythrocyte,leukocyte,and platelet counts were assessed using a hemocytometer;the CCK-8 assay was used to evaluate the proliferation of spleen T and B lymphocytes as well as the phagocytic index of macrophages;flow cytometry was performed to analyze the proportion of CD4+T cells,CD4+/CD8+T cell ratio,and NK cell ratio in splenocytes.Histopathological changes in the spleen and thymus were observed using HE staining;Western blot was conducted to check the protein expression levels of phosphatidylinositol 3-kinase(PI3K),p-PI3K,serine/threonine protein kinase(Akt),and p-Akt in the spleen.Results Compared with the normal group,the model group exhibited a significant decrease in body weight,spleen index,and thymus index(P＜0.05,P＜0.01,P＜0.001);reduced leukocyte and platelet counts(P＜0.001);decreased proliferation indices of macrophages,T lymphocytes,and B lymphocytes(P＜0.05,P＜0.001);lower proportions of CD4+T cells,CD4+/CD8+ratio,and NK cell ratio(P＜0.01,P＜0.001);significant pathological damage to the thymus and spleen;and downregulated expressions of p-PI3K and p-Akt proteins(P＜0.001).Compared with the model group,the low-dose bilobalide group showed increased platelet count,macrophage and T cell proliferation indices,CD4+T cell proportion,NK cell ratio,and expressions of p-PI3K and p-Akt proteins(P＜0.05).Compared with the model group,the high-dose bilobalide group exhibited significant increase in body weight(P＜0.05),spleen index(P＜0.01),thymus index(P＜0.05),leukocyte and platelet counts(P＜0.05),proliferation indices of macrophages,T lymphocytes,and B lymphocytes(P＜0.05,P＜0.01),CD4+T cell proportion(P＜0.05),CD4+/CD8+ratio(P＜0.05),NK cell ratio(P＜0.05),and p-PI3K and p-Akt protein expressions(P＜0.05).Additionally,both low-and high-dose bilobalide groups showed amelioration in thymus and spleen pathological damage.Compared with the low-dose bilobalide group,the high-dose bilobalide group demonstrated significantly increased body weight,leukocyte count,and NK cell ratio(P＜0.05).Conclusion Bilobalide can enhance both specific and nonspecific immune functions in CTX-induced immunosuppressed mice,and its mechanism of action may be related to the activation of the spleen PI3K/Akt signaling pathway.关键词
免疫功能低下/白果内酯/环磷酰胺/磷脂酰肌醇-3-羟激酶/丝氨酸苏氨酸蛋白激酶Key words
immunocompromise/bilobalide/cyclophosphamide/phosphatidylinositol-3-hydroxykinase/serine-threonine protein kinase分类
中医学引用本文复制引用
卫华琴,李苗..白果内酯改善环磷酰胺所致小鼠免疫功能低下及其相关机制的研究[J].湖南中医药大学学报,2025,45(4):624-630,7.基金项目
西北妇女儿童医院基础科研计划项目(202310045). （202310045）
