【摘要】 目的 探讨NK细胞在雷公藤甲素（TP）肝损伤过程中的动态变化及作用。方法 C57BL/6雌性小鼠分为对照组，TP给药(600μg·kg^-1)1、3、5、7 d组，抗NK1.1抗体与TP合用1、3、5、7 d组。在不同时间点收集小鼠血液，分离肝脏非实质细胞，通过流式细胞术检测NK细胞、CD4⁺/CD8⁺T细胞亚群及细胞因子（IFN-γ、IL-4）的时空变化。结果 TP处理后，肝脏NK细胞比例在1 d显著升高（P<0.05）,3～7 d时CD69⁺NK细胞持续增加（P<0.05）。细胞因子分泌呈现时间依赖性：5 d时IFN-γ⁺NK细胞比例升高（P<0.05），而1和7 d以IL4⁺NK细胞为主（P<0.05）。NK细胞耗竭显著降低血清丙氨酸氨基转移酶（Alanie Transaminase, ALT）水平（P<0.05），减少IFN-γ分泌（P<0.05），使肝脏NK细胞分泌的细胞因子向Th2偏倚（IFN-γ/IL-4比值降低，P<0.05）。此外，TP诱导外周血中CD4⁺T细胞持续增加（1～7 d均P<0.05）与CD8⁺T细胞选择性减少（3～5 d, P<0.05），导致CD4⁺/CD8⁺比率失衡。结论 肝脏NK细胞在TP肝损伤中发挥作用。更多还原

【Abstract】 Objective To explore the dynamic changes and roles of natural killer（NK） cells in the process of triptolide（TP）-induced liver injury. Methods Female C57BL/6 mice were divided into the control group, the 1, 3, 5, and 7 days of TP administration(600 μg·kg^-1) groups, and groups treated with anti-NK1.1 antibody combined with TP for 1, 3, 5, and 7days. At different time points, the blood of mice was collected and non-parenchymal cells in the liver were isolated for flow cytometry analysis of the temporal changes in NK cells, CD4⁺/CD8⁺ T cell subsets and cytokines（IFN-γ and IL-4）. Results After TP treatment, the proportion of liver NK cells significantly increased at day 1（P<0.05）, while CD69+ NK cells kept increasing from day 3 to 7（P<0.05）. NK cell depletion significantly reduced serum ALT levels（P<0.05） and inhibited IFN-γ production（P<0.05）, shifting NK cell-derived cytokines toward a Th2 bias（reduced IFN-γ/IL-4 ratio, P<0.05）.Additionally, TP induced a persistent increase in peripheral blood CD4⁺ T cells（days 1-7, P<0.05） and a selective decrease in CD8⁺ T cells（days 3-5, P<0.05）, leading to an imbalanced CD4⁺/CD8⁺ ratio. Conclusion Hepatic NK cells can contribute to TP-induced liver injury.更多还原