维康颗粒对乳腺癌小鼠肿瘤相关性疲劳的影响及代谢机制研究

Metabolic Mechanism of Weikang Granule on Cancer Related Fatigue in Mice with Breast Cancer

目的探讨维康颗粒(Weikang Granule,WG)对乳腺癌小鼠肿瘤相关性疲劳的影响及代谢机制。方法将40只成功接种4T1乳腺肿瘤细胞的小鼠分为肿瘤对照TC组(生理盐水灌胃,20 m L/kg,1次/日)、维康颗粒(WG)组、紫杉醇(PTX)组、维康颗粒+紫杉醇(WG+PTX)组,每组10只,给药组分别给予相应WG(6g/kg,灌胃,1次/日)及PTX(10 mg/kg,腹腔注射,隔日1次),连续干预21日。观察干预前及干预第10、20日力竭游泳时间。干预结束后取血,应用核磁共振氢谱(1H-NMR)技术获取小鼠代谢指纹图谱信息,采用PCA、PLSDA、OPLS-DA进行数据处理,观察各组血浆差异代谢物。结果与TC组比较,PTX组力竭游泳时间减少(P<0.01),瓜氨酸水平升高,肌醇、磷酸胆碱、异柠檬酸、甘油磷酸酯、亚油酸、谷氨酰胺、辅酶A、天冬氨酸、丝氨酸、高半胱氨酸、赤藓糖水平下降(P<0.01,P<0.05);WG组力竭游泳时间延长(P<0.01,P<0.05),甘油磷酸酯水平升高(P<0.01)。与PTX组比较,WG+PTX组力竭游泳时间延长(P<0.01),神经酸、辅酶A、磷酸烯醇丙酮酸、肌醇、赤藓糖水平升高(P<0.01,P<0.05)。结论维康颗粒具有减轻化疗相关性疲劳的作用,其机制与促进ATP生成,并加强磷酸戊糖途径、脂肪酸代谢、糖异生相关。

Objective To explore the metabolic mechanism of Weikang Granule（ WG） on cancer related fatigue in mice with breast cancer. Methods Forty successfully modeled mice established by subcutaneous injection of 4 T1 breast tumor cells were divided into four groups according to the tumor volume,tumor control（ TC） group（ NS,20 m L/kg,gastrogavage,qd）,PTX group（ paclitaxel,10 mg/kg,intraperitoneal injection,qod）,WG group（ WG,6 g/kg,gastrogavage,qd） and WG ＋ PTX group（ WG,6 g/kg gastrogavage,qd; paclitaxel,intraperitoneal injection,10 mg/kg,qod）,10 in each group,all intervention lasted for21 days. The exhausting swimming time（ EST） was observed before intervention,at day 10 and 20 of intervention. Blood was collected after intervention,the metabolic fingerprint was acquired by1H-NMR,the differential metabolites in the plasma were identified by PCA,PLS-DA,and OPLS-DA. Results Compared with TC group,the levels of citrulline were increased in PTX group,EST and the levels of inositol,choline phosphate,isocitric acid,glycerol phosphate,linoleic acid,glutamine,coenzyme A,aspartic acid,serine,homocysteine,erythrose were decreased in PTX group（ P 0. 01,P 0. 05）; EST and levels of glycerol phosphate were increased in WG group（P 0. 01,P 0. 05）. Compared with PTX group,EST and levels of nervonic acid,coenzyme A,phosphoenolpyruvate,inositol and erythrose were increased in WG ＋ PTX group（P 0. 01,P 0. 05）. Conclusions WG can alleviate the chemotherapy related fatigue,the mechanism might be related to promoting ATP production,and strengthening the pentose phosphate pathway,fatty acid metabolism,andgluconeogenesis.