【摘要】 目的 研究芪葛汤及其配方颗粒化学成分、入血成分及药效的一致性。方法 （1）采用高脂饮食诱导构建高脂血症大鼠模型。将70只SD雄性大鼠随机分为空白组、模型组、阳性药组(5 mg·kg^-1阿托伐他汀钙)及芪葛汤/芪葛汤配方颗粒低(4.5 g·kg^-1)、高剂量(9.0 g·kg^-1)组，每组10只。灌胃给药，每天1次，连续给药23 d。通过检测各组大鼠体质量、肝脏系数、血清血脂指标水平及观察大鼠肝脏HE染色及油红O染色情况，综合评价芪葛汤及其配方颗粒的抗高血脂药效。（2）运用超高效液相色谱-四极杆-静电场轨道阱高分辨质谱（UHPLC-Q-Orbitrap HRMS）技术分析芪葛汤及其配方颗粒的化学成分与入血成分；根据化合物精确相对分子质量、保留时间、二级碎片离子及与mzCloud、Chemspider等数据库、相关文献、对照品进行匹配鉴定成分；采用化学计量学方法评价芪葛汤及其配方颗粒化学成分与入血成分的一致性。结果 （1）空白组大鼠肝脏结构完整、肝细胞排列有序、无脂肪及脂滴堆积。模型组大鼠肝脏中肝细胞排列杂乱、空泡样脂肪变形明显、脂滴增多，大量弥漫分布的红染脂滴；经给药干预后，各给药组大鼠肝脏中肝细胞排列变整齐，脂肪堆积及脂滴数量减少、脂滴红染面积缩小。与空白组比较，模型组大鼠的体质量及肝脏系数、相对油红O染色阳性面积比明显增加（P<0.05,P<0.01），血清TC、TG、LDL-C水平明显升高（P<0.05,P<0.01）,HDL-C水平明显降低（P<0.01）。与模型组比较，各给药组体质量、相对油红O染色阳性面积比及芪葛汤低、高剂量组大鼠的肝脏系数明显减小（P<0.05,P<0.01），血清TG、TC、LDL-C水平明显降低（P<0.05,P<0.01）,HDL-C水平有升高趋势，但差异无统计学意义（P>0.05）。芪葛汤及其配方颗粒各给药组大鼠的体质量、肝脏系数、相对油红O染色阳性面积比及血清各血脂指标水平比较，差异无统计学意义（P>0.05）。（2）芪葛汤和芪葛汤配方颗粒共指认出87种化学成分和40种入血成分。以有监督的正交偏最小二乘法判别分析（OPLS-DA）筛选出芪葛汤及其配方颗粒显著差异化学成分15个，显著差异入血原型成分9个，其中葛根素芹菜糖苷、毛蕊异黄酮葡萄糖苷、芒柄花素、大豆苷、毛蕊异黄酮、橙皮素等入血成分差异缩小。结论 芪葛汤及其配方颗粒抗高血脂药效一致，芪葛汤及其配方颗粒中化学成分存在明显差异，但入血后二者化学成分差异缩小。更多还原

【Abstract】 Objective To investigate the consistency of chemical constituents, blood-absorbed components, and pharmacological effects between Qige Decoction and its formula granules. Methods（1） A hyperlipidemia rat model was established using a high-fat diet. Seventy SD male rats were randomly divided into seven groups（n=10 per group）:blank group,model group,positive drug group(atorvastatin calcium,5 mg·kg^-1),and low-dose(4.5 g·kg^-1) and high-dose(9.0 g·kg^-1) groups of Qige Decoction and its formula granules. The drugs were administered by gavage once daily for 23 consecutive days. The anti-hyperlipidemic efficacy of Qige Decoction and its formula granules was comprehensively evaluated by measuring body mass, liver index, serum lipid profile levels, and observing liver histopathology via HE staining and Oil Red O staining.（2） Ultra-high performance liquid chromatography-quadrupole-orbitrap high-resolution mass spectrometry（UHPLC-Q-Orbitrap HRMS） was employed to analyze the chemical constituents and blood-absorbed components of both Qige Decoction and its formula granules. Identification and characterization of components were performed based on accurate molecular weight,retention time,secondary fragment ions,databases（mzCloud,Chemspider）,relevant literature,and reference standards. Chemometric methods were used to evaluate the consistency of chemical constituents and blood-absorbed components between Qige Decoction and its formula granules. Results（1） The livers of rats in the blank control group showed intact structure,orderly arranged hepatocytes,and no fat or lipid droplet accumulation. In contrast,the model group exhibited disorganized hepatocyte arrangement,significant vacuolar fatty degeneration,increased lipid droplets,and extensive diffusely distributed red-stained lipid droplets in the liver. the arrangement of hepatocytes became more regular,with reduced fat accumulation,fewer lipid droplets,and smaller areas of red-stained lipid droplets in the all treatment groups model rats. Compared with the blank control group,the model group showed significantly increased body mass,liver index,and relative Oil Red O positive staining area ratio（P<0.05,P<0.01）,significantly elevated serum TC,TG and LDL-C levels（P<0.01）,and significantly decreased HDL-C levels（P<0.01）. Compared with the model group,all treatment groups showed significantly reduced body mass and relative Oil Red O positive staining area ratio, and the low-and high-dose Qige Decoction groups also showed a significant decrease in liver index（P<0.05,P<0.01）. Serum TG,TC,and LDL-C levels were significantly lowered（P<0.05, P<0.01）, and HDL-C levels showed an increasing trend,although the difference was not statistically significant（P>0.05） in all treatment groups. No statistically significant differences（P>0.05） were observed in body mass, liver index, relative Oil Red O positive staining area ratio, or serum lipid parameters between the corresponding dose groups of Qige Decoction and its formula granules.（2） A total of 87 chemical constituents and 40 blood-absorbed components were identified in both Qige Decoction and its formula granules. Supervised orthogonal partial least squares-discriminant analysis（OPLS-DA） screened 15 significantly different chemical constituents and 9 significantly different prototype blood-absorbed components between them. Notably, the differences in several blood-absorbed components, such as puerarin apioside, calycosin glucoside,formononetin, daidzin, calycosin, and hesperetin, were diminished post-absorption. Conclusion Qige Decoction and its formula granules exhibit consistent anti-hyperlipidemic efficacy. Although significant differences exist in their chemical profiles,these differences are reduced among the components that enter the bloodstream.更多还原