知母总皂苷通过花生四烯酸代谢改善丙酸睾酮诱导的大鼠前列腺增生  

Saponins extract of Anemarrhenae Rhizoma ameliorates testosterone-induced benign prostatic hyperplasia in rats via through arachidonic acid metabolism pathways

作　　者：谢琳琳 廖俊 尚影 曹晓彤 王斯琪 张腾 戴荣华[1] XIE Linlin;LIAO Jun;SHANG Ying;CAO Xiaotong;WANG Siqi;ZHANG Teng;DAI Ronghua(School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China)

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2021年第9期900-909,共10页Journal of Shenyang Pharmaceutical University

基　　金：国家自然科学基金资助项目(81872987)。

摘　　要：目的研究知母总皂苷对前列腺增生(benign prostatic hyperplasia,BPH)炎症的治疗作用及其潜在的作用机制。方法基于靶向代谢组学建立超高效液相色谱串联质谱法(ultra-fast liquid chromatography tandem mass spectrometry,UFLC-MS/MS)测定假手术组、BPH模型组、阳性对照组和知母总皂苷组大鼠血浆的花生四烯酸(arachidonic acid,AA)及其15种代谢物的含量变化。此外,本研究考察了各组大鼠的前列腺参数以及组织学形态的变化,从多维度研究知母总皂苷对BPH炎症的影响。结果建立的UFLC-MS/MS法在专属性、残留、线性、定量下限、准确度、精密度、提取回收率、基质效应和稳定性方面均符合生物样品分析要求,该方法快速、灵敏、可靠。采用此方法研究结果表明BPH发展过程中AA代谢紊乱,AA及15种代谢物含量显著增加。而知母总皂苷可有效下调BPH大鼠血浆中AA及15种代谢物的含量。此外,前列腺重量、前列腺指数及组织病理学结果均表明知母总皂苷可明显改善BPH炎症。结论知母总皂苷通过双重抑制脂氧合酶和环氧合酶代谢途径,下调AA及15种代谢物的含量,使AA代谢正常化,从而阻断和逆转BPH炎症。Objective To study the therapeutic effect of saponins extract of Anemarrhenae Rhizoma(SEAR) on benign prostatic hyperplasia(BPH) inflammation and its underlying mechanisms.Methods Ultra-fast liquid chromatography tandem mass spectrometry(UFLC-MS/MS) based on targeted metabolomics was established to simultaneously determine the levels of arachidonic acid(AA) and its fifteen metabolites in rat plasma samples.Furthermore, the changes of parameters and histological morphology of the prostate were also investigated to explore the effect of SEAR on BPH inflammation from multi-dimension.Results The UFLC-MS/MS method was fully validated in accordance with guidelines of biological sample analysis with respect to selectivity, residue analysis, linearity, lower limit of quantification, accuracy and precision, recovery, matrix effects, and stability.The method was proved to be rapid, sensitive and reliable.Based on targeted metabolomics study, findings of the research demonstrated that AA metabolism was disordered during the progression of BPH,and the level of AA and 15 metabolites remarkably increased.SEAR effectively down-regulated the amounts of AA and 15 metabolites in plasma.Furthermore, the results of prostate weight, prostate index and histopathology also revealed that SEAR significantly ameliorated BPH inflammation.Conclusion SEAR can down-regulate the production of AA and its metabolites though dual inhibition of lipoxygenase and cyclooxygenase metabolic pathways and normalize the AA metabolism, thereby blocking and reversing BPH inflammation.

关 键 词：前列腺增生 花生四烯酸代谢 脂氧合酶 环氧合酶 知母总皂苷 

分 类 号：R917[医药卫生—药物分析学]