[关键词]
[摘要]
目的 明确妇科再造丸(FKW)对气血两虚证的治疗作用,揭示母鸡油炙三七对FKW的增效机制。方法 小鼠随机分为对照组、模型组、复方阿胶浆(FFEJ,阳性药,10 mL·kg-1)组和FKW(含母鸡油炙三七)、含生三七的妇科再造丸(SFKW)、不含三七的妇科再造丸(WFKW)低、中、高剂量(0.34、0.67、1.35 g·kg-1)组,除对照组外,采用环磷酰胺法建立小鼠气血虚证模型。观察小鼠一般状态,检测脾脏、胸腺指数,采用血液分析仪检测血常规指标;ELISA检测血清中白蛋白(ALB)、白细胞介素1(IL-1)、丙氨酸氨基转移酶(ALT)、红细胞生成素(EPO)、天冬氨酸氨基转移酶(AST)水平;苏木精-伊红(HE)染色观察脾脏病理变化;非靶向代谢组学分析粪便样本中代谢物变化及所涉及代谢通路。结果 与模型组相比,各给药组可不同程度改善气血两虚证小鼠的一般状态、脾脏病理损伤、脏器指数及血常规异常(P<0.05、0.01),降低血清中ALB、ALT、AST、EPO、IL-1水平(P<0.05、0.01),且FKW疗效优于SFKW和WFKW,低剂量下母鸡油炙三七的增效作用最为显著(P<0.05、0.01)。代谢组学结果显示,FKW可显著回调28个与气血两虚证相关的差异代谢物,主要富集于初级胆汁酸生物合成和嘌呤代谢通路。FKW与SKFW组间进一步筛选出11个差异代谢物,主要涉及初级胆汁酸生物合成、苯丙氨酸代谢及维生素B6代谢等通路。结论 FKW可能通过调控初级胆汁酸生物合成和嘌呤代谢通路治疗气血两虚证;母鸡油炙三七能够增强FKW对气血两虚证的治疗作用,这种增效作用可能涉及调控初级胆汁酸生物合成、苯丙氨酸代谢、维生素B6代谢、嘌呤代谢及咖啡因代谢通路。
[Key word]
[Abstract]
Objective To explore the therapeutic mechanism of Fuke Zaizao Pills(FKW) for the syndrome of deficiency of both qi and blood, and to reveal the synergistic mechanism of hen oil-fried Panax notoginseng on FKW. Methods Mice were randomly divided into the control group, model group, Compound Ejiao Syrup(FFEJ, positive drug, 10 mL·kg-1) group, and FKW(containing hen oil-fried P. notoginseng), SFKW(containing raw P. notoginseng), and WFKW(without P. notoginseng) low, medium, and highdose(0.34, 0.67, 1.35 g·kg-1) groups. Except for the control group, a mouse model of syndrome of deficiency of both qi and blood was established by cyclophosphamide. The general state of mice, spleen and thymus indices, and blood routine indicators were observed. The levels of albumin(ALB), interleukin-1(IL-1), alanine aminotransferase(ALT), erythropoietin(EPO), and aspartate aminotransferase(AST) in serum were detected by ELISA. The pathological changes of the spleen were observed by hematoxylineosin(HE) staining. The changes in metabolites and involved metabolic pathways in fecal samples were analyzed by non-targeted metabolomics. Results Compared with the model group, all drug groups could improve the general state, spleen pathological damage, organ indices, and blood routine abnormalities of mice with syndrome of deficiency of both qi and blood to varying degrees(P < 0.05, 0.01), and reduce the levels of ALB, ALT, AST, EPO, and IL-1 in serum(P < 0.05, 0.01). The therapeutic effect of FKW was superior to that of SFKW and WFKW, and the enhancing effect of hen oil-fried P. notoginseng was most significant at the low dose(P < 0.05, 0.01). Metabolomics results showed that FKW could significantly regulate 28 differential metabolites related to syndrome of deficiency of both qi and blood, mainly enriched in primary bile acid biosynthesis and purine metabolism pathways. Further screening between FKW and SFKW groups identified 11 differential metabolites, mainly involved in primary bile acid biosynthesis, phenylalanine metabolism, and vitamin B6 metabolism pathways. Conclusion FKW exerts a therapeutic effect on syndrome of deficiency of both qi and blood, which may be related with regulating the primary bile acid biosynthesis and purine metabolism pathways. Hen oil-fried P. notoginseng can enhance the therapeutic effect of FKW on treating syndrome of deficiency of both qi and blood, and its synergistic mechanism may be associated with the regulation of multiple metabolic pathways, including primary bile acid biosynthesis, phenylalanine metabolism, vitamin B6 metabolism, purine metabolism, and caffeine metabolism.
[中图分类号]
R965
[基金项目]
贵州省科技计划项目(黔科合基础-ZK[2024]重点076号); 贵州省中医药管理局中医药、民族医药科学技术研究专项课题(QZYY-2026-212); 贵州中医药大学中药民族药产地加工与炮制科技创新人才团队建设项目(贵中医TD合字[2024]001号); 贵州省苗医药全省重点实验室(黔科合平台[2025]018号)