正元胶囊防治肺腺癌A549移植瘤裸鼠化疗相关性疲劳的疗效及机制研究

Therapeutic Effects of Zhengyuan Capsules for Chemotherapy-Related Fatigue in Nude Mice with Lung Adenocarcinoma A549 Xenografts and Its Mechanism

【目的】探讨正元胶囊防治化疗相关疲劳的疗效及作用机制。【方法】将80只BALB/c-nu裸鼠分为正常组、模型组、顺铂组、联合治疗组,每组20只。复制肺腺癌A549移植瘤裸鼠模型。成功造模后,顺铂组给予顺铂5 mg/kg腹腔注射,每3 d1次;联合治疗组给予裸鼠顺铂5 mg/kg腹腔注射,每3 d 1次,及正元胶囊1.8 g/kg灌胃,每天1次;正常组和模型组给予相应体积的生理盐水灌胃。连续21 d。通过力竭游泳实验、悬尾实验、旷场实验评估疲劳程度。检测各组裸鼠的肝糖原含量、外周血象与外周血肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、粒细胞集落刺激因子(G-CSF)、促红细胞生成素(EPO)、白细胞介素3(IL-3)等细胞因子水平以及骨髓有核细胞计数,观察骨髓细胞涂片。【结果】顺铂组化疗后出现动物行为学的恶化。与顺铂组比较,联合治疗组裸鼠的力竭游泳时间延长,悬尾不动时间缩短,旷场实验总运动距离延长、平均运动速度提高,肝糖原含量增加,外周血白细胞(WBC)、血红蛋白(HGB)和骨髓有核细胞增加,TNF-α和IL-6水平降低,G-CSF、EPO及IL-3水平升高(P<0.05或P<0.01或P<0.001)。【结论】正元胶囊可有效改善肺腺癌A549移植瘤裸鼠化疗相关疲劳症状,其机制可能与增加肝糖原储备,减轻化疗后裸鼠的骨髓抑制,降低血清中炎症相关细胞因子TNF-α和IL-6的含量,同时提高与骨髓造血功能相关的集落刺激生长因子G-CSF、EPO及IL-3水平有关。

Objective To explore the therapeutic effects of Zhengyuan Capsules(a registered proprietary Chinese medicine)for chemotherapy-related fatigue(CRF)and its mechanism.Methods Eighty BALB/c-nu nude mice were randomly divided into normal group,model group,cisplatin group and combination treatment group,20 nude mice in each group.The nude mouse model with lung adenocarcinoma A549 xenografts was established.After successful modeling,the cisplatin group was given intraperitoneal injection of 5 mg/kg of cisplatin every 3 days,the combination treatment group was given an intraperitoneal injection of 5 mg/kg of cisplatin every 3 days and intragastric administration of 1.8 g/kg of Zhengyuan Capsules each day.The normal group and model group were given intragastric administration of the same volume of normal saline.The treatment lasted 21 days.The forcedswimming test,tail suspension test and open field test were carried out for evaluating fatigue degree,meanwhile,the hepatic glycogen content,peripheral hemogram,the levels of cell factors including tumor necrosis factorα(TNF-α),interleukin 6(IL-6),granulocyte colony-stimulating factor(G-CSF),erythropoietin(EPO),interleukin 3(IL-3)and bone marrow nucleated cell count were detected and the bone marrow cell smear was observed in various groups.Results The behavior disorder results in CRF mice tended to worsen in the cisplatin group.Compared with the cisplatin group,the longer exhaustive swimming time,shorter immobility time during tail suspension test,longer total movement distance and higher average moving speed during open field test,increased hepatic glycogen level,higher white blood cell count,henroglobin(HGB)and bone marrow nucleated cell counts,reduced TNF-αand IL-6 levels,increased G-CSF,EPO and IL-3 levels were exhibited in the combination treatment group(P<0.05 or P<0.01 or P<0.001).Conclusion Zhengyuan Capsules have therapeutic effects on alleviating the cisplatin-induced CRF in the mice,and its mechanism is related with enhancing the post-chemotherapy hepatic glycogen content,reducing bone marrow suppression,and decreasing the serum levels of inflammation-related factors TNF-αand IL-6,and increasing the serum levels of marrow hemopoietic function-related colony-stimulating factors G-CSF,EPO and IL-3.