[關鍵詞]
[摘要]
目的 從代謝調控的角度探討保利爾膠囊對高脂血癥大鼠的調血脂作用及對內源性代謝物的影響。方法 采用高脂飼料喂養(yǎng)4周的方法制備高脂血癥大鼠模型,對照組喂飼普通飼料,造模成功大鼠隨機分為模型組、阿托伐他汀陽性對照組(1.8 mg·kg-1,臨床等效劑量)及保利爾膠囊低、中、高劑量(270、810、2 430 mg·kg-1,分別相當于1/3、1倍、3倍臨床劑量)組,各組大鼠分別ig給藥,對照組和模型組ig等體積蒸餾水,連續(xù)給藥8周。每2周測定大鼠體質量,給藥8周后測定各組大鼠血漿脂質生化指標,包括總膽固醇(TC)、三酰甘油(TG)、低密度脂蛋白膽固醇(LDL-C)、高密度脂蛋白膽固醇(HDL-C);蘇木素-伊紅(HE)染色觀察大鼠肝組織病理改變;采用超高效液相色譜-四極桿飛行時間質譜技術(UHPLC-Q-TOF-MS)對大鼠血漿代謝物進行檢測,篩選保利爾膠囊對高脂血癥大鼠作用的差異代謝物,分析其涉及的代謝通路。結果 保利爾膠囊能夠有效控制高脂血癥大鼠的體質量,顯著影響血漿中TC、TG、LDL-C和HDL-C的含量;代謝組學結果顯示,高脂血癥大鼠血漿中共篩選出56個差異代謝物,主要涉及甘油磷脂代謝、花生四烯酸代謝、亞油酸代謝和精氨酸代謝等代謝通路。結論 保利爾膠囊能夠改善高脂血癥大鼠的血脂異常,其作用機制主要與體內甘油磷脂代謝、花生四烯酸代謝、亞油酸代謝和精氨酸代謝等通路有關。
[Key word]
[Abstract]
Objective To explore the lipid-lowering effect of Baolile Capsules on hyperlipidemic rats and their effect on endogenous metabolites from the perspective of metabolic regulation. Methods A high-fat diet was used to prepare a rat model of hyperlipidemia for four weeks. The control group was fed with regular diet, and the successfully modeled rats were randomly divided into a model group, an atorvastatin positive control group (1.8 mg·kg-1, clinical equivalent dose), and low, medium, and high dose groups of Baolil Capsules (270, 810, 2 430 mg·kg-1, equivalent to 1/3, 1, and 3 times the clinical dose, respectively). Each group of rats was given ig, while the control group and model group were given ig of distilled water of equal volume for eight consecutive weeks. Measure the body mass of rats every two weeks, and after eight weeks of administration, measure the plasma lipid biochemical indicators of each group of rats, including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Observation of pathological changes in rat liver tissue using hematoxylin eosin (HE) staining, ultra high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) technology was used to detect metabolites in rat plasma, screen for differential metabolites in the effects of Baolile Capsules on hyperlipidemic rats, and analyze the metabolic pathways involved. Results Baolile Capsules can effectively control the body mass of hyperlipidemic rats and significantly affect the levels of TC, TG, LDL-C, and HDL-C in plasma. Metabolomics results showed that a total of 56 differential metabolites were screened from the plasma of hyperlipidemic rats, mainly involving metabolic pathways such as glycerophospholipid metabolism, arachidonic acid metabolism, linoleic acid metabolism, and arginine metabolism. Conclusion Baolile Capsules can improve blood lipid abnormalities in hyperlipidemic rats, and their mechanism of action is mainly related to pathways such as glycerophospholipid metabolism, arachidonic acid metabolism, linoleic acid metabolism, and arginine metabolism in the body.
[中圖分類號]
R285.5
[基金項目]
國家自然青年基金項目(82104284,82204509);通遼市科技計劃項目(TL2023YF010);內蒙古自治區(qū)科技計劃項目(2020GG0199)