目的 探讨复方阿胶浆治疗癌因性疲乏（CRF）的作用及潜在机制。方法 （1）药效实验：构建肺癌原位、结肠腺癌及白血病诱发的CRF小鼠模型，肺癌原位和结肠腺癌模型鼠接种7 d后、白血病模型鼠接种3 d后，进行转棒实验筛选造模成功的小鼠，按转棒时间均衡随机分为模型组、百令胶囊(2.3 g·kg^-1)组和复方阿胶浆3.4、6.8、13.6 g·kg^-1组，对照组不造模。ig给药，每天1次，连续给药14 d。检测给药前、给药第7、14天小鼠的转棒时间，末次转棒后采集血清和骨骼肌，采用全自动生化分析仪测定血清尿素氮（BUN）、肌酸激酶（CK）、白细胞介素1（IL-1）和肿瘤坏死因子α（TNF-α）水平，试剂盒法检测骨骼肌超氧化物歧化酶（SOD）、乳酸脱氢酶（LDH）水平。（2）功能相关实验：建立环磷酰胺致大鼠骨髓抑制模型，分为模型组、利可君片(0.01 g·kg^-1)组和复方阿胶浆2.3、4.6、9.2 g·kg^-1组，对照组不造模，ig给药，每天1次，连续11 d；于给药第5、11天分别剖杀半数动物，检测当天骨髓和外周血中白细胞（WBC）、血红蛋白（HGB）和血小板（PLT）含量；建立环磷酰胺和肺癌原位癌诱发的小鼠免疫力低下模型，末次处理时取脾脏、胸腺和肝脏称质量，计算脏器指数，进行碳廓清实验检测廓清指数（κ）和吞噬指数（α）。结果 （1）药效实验：与对照组比较，3种CRF模型组小鼠转棒时间给药前、给药7和14 d均显著缩短（P<0.01），疲乏相关因子BUN、SOD和LDH水平均显著降低，CK、IL-1和TNF-α水平均显著升高（P<0.05、0.01）；与模型组比较，复方阿胶浆在6.8、13.6 g·kg^-1剂量下给药14 d后均显著延长3种CRF模型小鼠的转棒时间（P<0.05、0.01），在13.6 g·kg^-1剂量下显著逆转模型小鼠体内BUN、SOD和LDH水平的降低，CK、IL-1和TNF-α水平的升高（P<0.05、0.01）。（2）功能相关实验：与对照组比较，骨髓抑制模型组大鼠给药第5、11天骨髓和外周血中WBC、HGB和PLT含量均显著下降（P<0.01）,2种免疫低下模型组小鼠胸腺指数、脾脏指数、κ和α显著降低（P<0.05、0.01）；与模型组比，复方阿胶浆给药11 d后显著升高骨髓抑制模型大鼠骨髓和外周血中WBC、HGB和PLT含量（P<0.05、0.01），给药14 d后显著提升免疫低下模型小鼠胸腺指数、脾脏指数、κ和α（P<0.05、0.01）。结论 复方阿胶浆可有效延长3种CRF模型小鼠的抗疲劳能力，逆转模型小鼠体内癌因性疲乏相关因子水平的变化，进而改善小鼠癌因性疲乏，改善作用与其生血生髓、扶正祛邪功效相关。

Objective To explore the pharmacodynamic effect and potential mechanism of Fufang Ejiao Jiang in the treatment of cancer-related fatigue（CRF）. Methods According to the primary syndrome and auxiliary syndrome test, they were divided into normal control group, model control group, positive drug group, Fufang Ejiao Jiang low, medium and high dose groups.①Primary syndrome test: Mice models of carcinomatous fatigue induced by lung cancer in situ, colorectal adenocarcinoma and leukemia were constructed, and rotarod test time of mice before administration, 7 and 14 d of administration were detected. The contents of urea nitrogen（BUN）, creatine kinase（CK）, interleukin I（IL-1）, tumor necrosis factor α（TNF-α）, superoxide dismutase（SOD） and lactate dehydrogenase（LDH） were measured in serum and skeletal muscle after the last rotation.② Adjuvant syndrome test: cyclophosphamide induced myelosuppression model of rats was established, and half of the rats were killed on the 5 th and 11 th d of administration, respectively, and the contents of white blood cells（WBC）, hemoglobin（HGB） and platelets（PLT） in bone marrow and peripheral blood were detected on the same day. A mice model of immunosuppression induced by cyclophosphamide and carcinoma in situ was established. The spleen, thymus and liver were weighed to calculate the organ coefficient, clearance index（κ） and phagocytosis index（α） at the last treatment. Results①Primary syndrome test: Compared with the normal control group, the rod turning time of the three kinds of CRF model control group was significantly shortened before administration, 7 and 14 d after administration（P < 0.01）, the levels of BUN, SOD and LDH related factors were significantly decreased, and the levels of CK, IL-1 and TNF-α were significantly increased（P < 0.05 and 0.01）. Compared with the model control group, the rod turning time of the three kinds of CRF model mice was significantly prolonged after 14 d of administration at the dose of 6.8 and 13.6 g·kg^-1（P < 0.05 and 0.01）. At doses of 3.4, 6.8, 13.6 g·kg^-1, the levels of BUN, SOD and LDH were significantly reversed, and the levels of CK, IL-1 and TNF-α were inhibited（P< 0.05 and 0.01）.②Auxiliary syndrome test: Compared with normal control group, WBC, HGB and PLT contents in bone marrow and peripheral blood of rats in myelosuppression model group were significantly decreased on the 5 th and 11 th d of administration（P < 0.01）, while thymus coefficient, spleen coefficient, κ and α of mice in the two kinds of immunosuppression model group were significantly decreased（P < 0.05 and 0.01）. Compared with the model control group, the contents of WBC, HGB and PLT in bone marrow and peripheral blood of myelosuppression model rats were significantly increased after 11 d of administration at doses of 3.2, 4.6 and 9.6 g·kg^-1（P < 0.05 and 0.01）. After 14 d of administration, gland coefficient, spleen coefficient, κ and α were significantly increased in immunocompromised mice（P < 0.05 and 0.01）. Conclusion The Fufang Ejiao Jiang can effectively prolong the anti-fatigue ability of the three CRF model mice, reverse the changes of CRF related factors in the model mice, and then improve the CRF of the mice, and the improvement is related to the blood and marrow generation, strengthening and dispelling evil effects.

R285.5

国家科技创业领军人才(SQ2024RA3E000198); 广东省药物非临床评价与研究重点实验室(2023B1212070029); 广东省重大人才工程项目(2021TY060021)