Wang Xuan, Sun Qiqi, Li Jianrong, Lai Baoyong, Pei Xiaohua, Chen Nana
Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care Hospital, Beijing, China.
The Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing, China.
Front Oncol. 2025 Apr 28;15:1515498. doi: 10.3389/fonc.2025.1515498. eCollection 2025.
Based on the murine model, this study explored the efficacy of Fangxia-Dihuang Decoction (FXDH) in interfering with cognitive impairment induced by doxorubicin (DOX) after chemotherapy for breast cancer.
Build 4T1 breast cancer xenograft tumor model in Balb/c mice, intraperitoneal injection of DOX (5mg/kg) once a week, build the model of DOX induced chemotherapy related cognitive impairment (CRCI), and the administration lasted for three weeks. From the first week, while DOX was given, FXDH was given high, medium and low doses by gavage every day. Conduct Y-maze and Novel object recognition (NOR) tests, detect inflammatory factors and oxidative stress-related indicators in serum and hippocampus, observe neuroinflammation and neurodegenerative changes through immunofluorescence and Nissl staining. Observation of heart and liver injury through blood routine and cardiac Hematoxylin-Eosin(HE)Staining.
Administration of FXDH significantly improved cognitive impairment in mice. FXDH reduced the levels of pro-inflammatory cytokines IL-6, IL-12p70, and TNF-α (P<0.05), and increased the levels of anti-inflammatory cytokines IL-10 and IL-4 (P<0.05). FXDH increased the levels of GSH, GSH-PX, SOD, and CAT in serum and hippocampus (P<0.05), and decreased the level of MDA (P<0.05). The results of Nissl staining and immunofluorescence staining showed that FXDH improved the neurodegenerative lesions caused by DOX and the neuroinflammatory response in the hippocampus (P<0.05). The intermediate dose group of FXDH showed better efficacy. The results of blood routine and cardiac HE staining showed that compared with the 4T1 group, the serum ALT, AST, CK, LDH, and CKMB in DOX group mice were significantly increased (P<0.05). After FXDH administration, all indicators in mice were decreased, but there was no statistical difference. FXDH improved the disordered arrangement of myocardial cells, uneven cytoplasmic staining, and loose and disordered arrangement of myocardial fibers caused by DOX.
In the animal model, FXDH has the effect of anti-cognitive impairment after chemotherapy for breast cancer, and can improve the DOX induced learning, memory and cognitive impairment in mice. FXDH can reverse DOX induced neuroinflammation by improving the neurodegenerative changes caused by DOX, reducing pro-inflammatory cytokine levels in mouse serum and hippocampus, increasing anti-inflammatory cytokine levels, and reducing oxidative stress response.
基于小鼠模型，本研究探讨了防夏地黄汤（FXDH）对乳腺癌化疗后阿霉素（DOX）诱导的认知功能障碍的干预作用。
在Balb/c小鼠中建立4T1乳腺癌异种移植瘤模型，每周腹腔注射一次DOX（5mg/kg），建立DOX诱导的化疗相关认知功能障碍（CRCI）模型，给药持续3周。从第1周开始，在给予DOX的同时，每天分别灌胃给予FXDH高、中、低剂量。进行Y迷宫和新物体识别（NOR）试验，检测血清和海马中的炎症因子及氧化应激相关指标，通过免疫荧光和尼氏染色观察神经炎症和神经退行性变化。通过血常规和心脏苏木精-伊红（HE）染色观察心脏和肝脏损伤。
给予FXDH可显著改善小鼠的认知功能障碍。FXDH降低了促炎细胞因子IL-6、IL-12p70和TNF-α的水平（P<0.05），并提高了抗炎细胞因子IL-10和IL-4的水平（P<0.05）。FXDH提高了血清和海马中GSH、GSH-PX、SOD和CAT的水平（P<0.05），并降低了MDA的水平（P<0.05）。尼氏染色和免疫荧光染色结果显示，FXDH改善了DOX引起的神经退行性病变和海马中的神经炎症反应（P<0.05）。FXDH中剂量组疗效更佳。血常规和心脏HE染色结果显示，与4T1组相比，DOX组小鼠血清ALT、AST、CK、LDH和CKMB显著升高（P<0.05）。给予FXDH后，小鼠各项指标均降低，但无统计学差异。FXDH改善了DOX引起的心肌细胞排列紊乱、细胞质染色不均以及心肌纤维排列疏松紊乱的情况。
在动物模型中，FXDH对乳腺癌化疗后抗认知功能障碍有作用，可改善DOX诱导的小鼠学习、记忆和认知功能障碍。FXDH可通过改善DOX引起的神经退行性变化、降低小鼠血清和海马中促炎细胞因子水平、提高抗炎细胞因子水平以及减轻氧化应激反应来逆转DOX诱导的神经炎症。
