目的 研究新生化顆粒對急性血瘀大鼠血漿中內(nèi)源性代謝物的影響，探討新生化顆粒治療急性血瘀證的可能機(jī)制。方法 將50只SD大鼠隨機(jī)分為對照組、模型組、復(fù)方丹參滴丸（陽性藥，0.10 g·kg^-1）組和新生化顆粒低、高劑量（4.86、9.72 g·kg^-1）組，給藥體積10 mL·kg^-1，對照組和模型組大鼠ig給予等體積0.5%羧甲基纖維素鈉（CMC-Na），每天早晚各ig給藥1次，共7次。第5次給藥后，除對照組外，采用sc鹽酸腎上腺素和冰水浴制備大鼠急性血瘀模型。通過測定全血黏度（WBV）、血漿黏度（PV）、活化部分凝血活酶時間（APTT）、凝血酶原時間（PT）、纖維蛋白原（FIB）和凝血酶時間（TT），觀察不同劑量的新生化顆粒對急性血瘀大鼠血液流變學(xué)和凝血功能的影響；采用超高效液相色譜-四極桿飛行時間質(zhì)譜聯(lián)用（UHPLCQTOF-MS）法檢測各組大鼠血漿中的內(nèi)源性代謝物，通過多變量統(tǒng)計分析篩選潛在生物標(biāo)志物，結(jié)合質(zhì)譜信息、數(shù)據(jù)庫檢索和標(biāo)準(zhǔn)品比對鑒定潛在生物標(biāo)志物，并將鑒定到的生物標(biāo)志物導(dǎo)入MetaboAnalyst 5.0數(shù)據(jù)庫推測其可能的代謝通路。結(jié)果 與模型組比較，新生化顆粒顯著降低急性血瘀大鼠WBV、PV和FIB，顯著延長APTT、PT和TT（P＜0.05、0.01）。代謝組學(xué)結(jié)果顯示，從急性血瘀大鼠血漿中共鑒定出21個差異代謝物（準(zhǔn)確鑒定7個），與對照組比較，模型組大鼠血漿中乳酸、肉堿和肌酐等10個內(nèi)源性代謝物顯著上調(diào)，蘋果酸、琥珀酸和色胺等11個內(nèi)源性代謝物顯著下調(diào)（P＜0.05、0.01）；除了硫酸吲哚酚和脫氧胞苷外，新生化顆粒對其他19個生物標(biāo)志物均有顯著回調(diào)作用（P＜0.05、0.01）。這些標(biāo)志物主要涉及苯丙氨酸、酪氨酸和色氨酸生物合成、苯丙氨酸代謝、亞油酸代謝、三羧酸循環(huán)和色氨酸代謝。結(jié)論 新生化顆粒對急性血瘀大鼠體內(nèi)紊亂代謝物有較好的回調(diào)作用，其作用機(jī)制主要與調(diào)節(jié)苯丙氨酸、酪氨酸和色氨酸生物合成，苯丙氨酸代謝，亞油酸代謝，三羧酸循環(huán)和色氨酸代謝通路有關(guān)。

Objective To explore the effects of Xinshenghua Granules on endogenous metabolites in rats with acute blood stasis syndrome, and to investigate the possible mechanism of Xinshenghua Granules for promoting blood circulation on acute blood stasis rats. Methods Tatolly 50 SD rats were randomly divided into control group, model group, compound Danshen Dripping Pills (positive drug, 0.10 g·kg^-1) group and Xinshenghua Granules low-dose and high-dose groups (4.86 and 9.72 g·kg^-1). The volume of administration was 10 mL·kg^-1. Intragastrically, once in the morning and evening, for seven times in total. After the fifth administration, except for the control group, the acute blood stasis model of rats were induced by ice water bath and subcutaneous injection of adrenaline. To evaluate the effects of promoting blood circulation, whole blood viscosity (WBV), plasma viscosity (PV), activated partial thrombin time (APTT), prothrombin time (PT), fibrinogen (FIB) and thrombin time (TT) in different groups were determined. UHPLC-QTOF-MS was applied to investigate the plasma metabolomics changes of acute blood stasis rats, and multivariate statistical analysis was used to screen the potential biomarkers, then the potential biomarkers were identified via database querying and comparison of reference standards, and finally the related metabolic pathways were discovered via MetaboAnalyst 5.0 software. Results Xinshenghua Granules obviously decreased WBV, PV, and FIB, while promoted the APTT, PT and TT (P < 0.05, 0.01). Totally 21 potential biomarkers were identified from blood stasis rats. Compared with control group, the levels of 10 metabolites (such as lactic acid, carnitine and creatinine) increased in model group; while the levels of 11 metabolites (such as malic acid, succinic acid and tryptamine) inclined in model group (P < 0.05, 0.01). Except for indoxyl-sulfate and deoxycytidine, the disturbed levels of other 19 metabolites could be reversed to normal-like levels after the drug treatment of Xinshenghua Granules (P < 0.05, 0.01). The mainly metabolic pathways were involved with phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, linoleic acid metabolism, TCA cycle and tryptophan metabolism. Conclusion Xinshenghua Granules could exert the effects of promoting blood circulation on blood stasis rats by regulating the disturbed endogenous metabolites and the related metabolic pathways.

R285.5