基于UPLC-Q/TOF-MS的丹参-川芎对局灶性脑缺血大鼠保护作用的脂质组学研究
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摘要
目的研究丹参-川芎水煎液冻干物对局灶性脑缺血模型大鼠脂质代谢异常的调节作用。方法采用线栓法复制大鼠局灶性脑缺血模型,将SD大鼠随机分为对照组、假手术组、模型组及丹参-川芎干预组。末次给药后采集血浆,采用超高效液相色谱四级杆飞行时间质谱联用仪(UPLC-Q/TOF-MS)进行血浆脂质组学研究,采用正交偏最小二乘判别分析(OPLS-DA)处理脂质组学数据,考察丹参-川芎干预前后脂质代谢物组变化。结果成功复制了大鼠局灶性脑缺血模型,丹参-川芎水煎液冻干物对局灶性脑缺血大鼠异常脂质代谢表现出明显的改善作用,大鼠脑缺血损伤血浆脂质标志物为PS(21:0/0:0)、PG(12:0/17:0)、C16 sphinganine,phytosphingosine、PE [18:1(9Z)/0:0]、PC(16:1/2:0)、PC(0:0/18:0)、PC(16:1/0:0)、PC(16:0/0:0)、PC(18:2/0:0)、PC(18:1/0:0)、PC(18:0/0:0)、PC(20:5/0:0)。结论丹参川芎水煎液冻干物具有脑缺血损伤保护作用,其机制可能与其对脂质,尤其是磷脂酰胆碱(PC)的调节有关。
Objective To study the regulating effect of freeze-dried substances of Salvia miltiorrhiza and Ligusticum chuanxiong Decoction on lipid metabolism abnormality in focal cerebral ischemia rats.Methods The focal cerebral ischemia rat model was established by monofilament method.The rats were randomly divided into normal group,sham operation group,model group,and drug treatment group.Plasma was collected after the last dosage and UPLC-Q/TOF-MS was used to study the plasma lipidomics.The lipidomics data were analyzed by orthogonal partial least square discriminant analysis(OPLS-DA),and the lipid metabolites changes were examined before and after the intervention of S.miltiorrhiza and L.chuanxiong.Results The focal cerebral ischemia rat model was successfully repeated.The S.miltiorrhiza and L.chuanxiong Decoction freeze-dried substances obviously reversed the abnormal lipid metabolism profile in the focal cerebral ischemia rat model.The plasma lipid biomarkers of ischemia injury rat were PS(21:0/0:0),PG(12:0/17:0),C16 sphinganine,phytosphingosine,PE [18:1(9 Z)/0:0],PC(16:1/2:0),PC(0:0/18:0),PC(16:1/0:0),PC(16:0/0:0),PC(18:2/0:0),PC(18:1/0:0),PC(18:0/0:0),and PC(20:5/0:0),respectively.Conclusion S.miltiorrhiza and L.chuanxiong Decoction freeze-dried substances have protective effects on cerebral ischemia injury,which may be related to the regulation of abnormal lipid metabolism,especially for phosphatidylcholines(PCs).
Objective To study the regulating effect of freeze-dried substances of Salvia miltiorrhiza and Ligusticum chuanxiong Decoction on lipid metabolism abnormality in focal cerebral ischemia rats.Methods The focal cerebral ischemia rat model was established by monofilament method.The rats were randomly divided into normal group,sham operation group,model group,and drug treatment group.Plasma was collected after the last dosage and UPLC-Q/TOF-MS was used to study the plasma lipidomics.The lipidomics data were analyzed by orthogonal partial least square discriminant analysis(OPLS-DA),and the lipid metabolites changes were examined before and after the intervention of S.miltiorrhiza and L.chuanxiong.Results The focal cerebral ischemia rat model was successfully repeated.The S.miltiorrhiza and L.chuanxiong Decoction freeze-dried substances obviously reversed the abnormal lipid metabolism profile in the focal cerebral ischemia rat model.The plasma lipid biomarkers of ischemia injury rat were PS(21:0/0:0),PG(12:0/17:0),C16 sphinganine,phytosphingosine,PE [18:1(9 Z)/0:0],PC(16:1/2:0),PC(0:0/18:0),PC(16:1/0:0),PC(16:0/0:0),PC(18:2/0:0),PC(18:1/0:0),PC(18:0/0:0),and PC(20:5/0:0),respectively.Conclusion S.miltiorrhiza and L.chuanxiong Decoction freeze-dried substances have protective effects on cerebral ischemia injury,which may be related to the regulation of abnormal lipid metabolism,especially for phosphatidylcholines(PCs).
引文
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[11]赖宝林.芎冰微乳鼻腔给药的脑靶向性及脑局部PK-PD结合模型研究[D].广州:广州中医药大学,2011.
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[13]芦晋,任雪,刘相良,等.超高效液相色谱-四极杆-静电场轨道阱质谱联用法用于宫颈癌患者尿液代谢组学研究[J].分析化学,2018,46(1):67-73.
[14]Lin S N,Horning E C.Analysis of long-chain acids or human plasma phosphatidylcholines(lecithins)and cholesteryl esters by glass open tubular capillary column gas chromatography for stroke patients and for normal subjects[J].J Chromatogr,1975,112:483-497.
[15]Rabiei Z,Bigdeli M R,Mohagheghi F.Effect of dietary virgin olive oil on infarct volume and brain ceramide,cerebroside and phosphatidylcholine levels in rat stroke model[J].J Shahrekord Univ Med Sci,2013,15(1):23-31.
[16]Koizumi S,Yamamoto S,Hayasaka T,et al.Imaging mass spectrometry revealed the production of lysophosphatidylcholine in the injured ischemic rat brain[J].Neuroscience,2010,168(1)219-225.
[17]Davies L,Fassbender K,Walter S.Sphingolipids in Neuroinflammation[M].Berlin:Springer Vienna,2013.
[18]Zheng W J,Kollmeyer J,Symolon H,et al.Ceramides and other bioactive sphingolipid backbones in health and disease:Lipidomic analysis,metabolism and roles in membrane structure,dynamics,signaling and autophagy[J].Biochim Biophys Acta,2006,1758(12):1864-1884.
[19]Khan M,Ekhon B K,Sekhon C S,et al.Sphingolipids in rat model of transient focal cerebral ischemia:Implication for stroke injury[J].J Neurochem,2008,81(S1):108-111.
[20]Novgorodov S A,Gudz T I.Ceramide and mitochondria in ischemic brain injury[J].Int J Biochem Mol Biol,2011,2(4):347-361.
[2]马焕文,郭述苏,许荣家.缺血性中风红细胞膜流动性与膜脂质及血脂关系的研究[J].中风与神经疾病杂志,1998,15(4):219-221.
[3]Phillis J W,O’Regan M H.A potentially critical role of phospholipases in central nervous system ischemic,traumatic,and neurodegenerative disorders[J].Brain Res Rev,2004,44(1):13-47.
[4]Fuchs B,Schiller J.Lysophospholipids:Their generation,physiological role and detection.Are they important disease markers?[J].Mini-Rev Med Chem,2014,9(3):368-378.
[5]Sethi S,Brietzke E.Recent advances in lipidomics:Analytical and clinical perspectives[J].Prostaglandins Other Lipid Mediators,2017(S128/129):8-16.
[6]朱建伟,郑广娟.川芎,丹参及其配伍对大鼠脑缺血再灌注损伤的不同影响[J].时珍国医国药,1997,8(3):232-233.
[7]张曦,陈明津.丹参川芎治疗急性缺血性脑卒中的效果分析[J].吉林医学,2016,37(10):2417-2418.
[8]杨倩,吕莉莉,孙蓉.基于网络药理学的丹参川芎嗪注射液作用机制分析[J].中草药,2018,49(11):2606-2613.
[9]许珍晶.丹参川芎嗪注射液治疗后循环缺血性眩晕的临床评价[J].药物评价研究,2017,40(9):1334-1337.
[10]张翠英.丹参川芎对药及其组方冠心宁制剂治疗心脑血管疾病的研究进展[J].中成药,2017,39(5):1018-1024.
[11]赖宝林.芎冰微乳鼻腔给药的脑靶向性及脑局部PK-PD结合模型研究[D].广州:广州中医药大学,2011.
[12]杨秀娟,邓毅,吴国霞,等.基于UPLC-Q-TOF/MS的归身和归尾补血机制的代谢组学初步研究[J].天然产物研究与开发,2018,30(2):176-184.
[13]芦晋,任雪,刘相良,等.超高效液相色谱-四极杆-静电场轨道阱质谱联用法用于宫颈癌患者尿液代谢组学研究[J].分析化学,2018,46(1):67-73.
[14]Lin S N,Horning E C.Analysis of long-chain acids or human plasma phosphatidylcholines(lecithins)and cholesteryl esters by glass open tubular capillary column gas chromatography for stroke patients and for normal subjects[J].J Chromatogr,1975,112:483-497.
[15]Rabiei Z,Bigdeli M R,Mohagheghi F.Effect of dietary virgin olive oil on infarct volume and brain ceramide,cerebroside and phosphatidylcholine levels in rat stroke model[J].J Shahrekord Univ Med Sci,2013,15(1):23-31.
[16]Koizumi S,Yamamoto S,Hayasaka T,et al.Imaging mass spectrometry revealed the production of lysophosphatidylcholine in the injured ischemic rat brain[J].Neuroscience,2010,168(1)219-225.
[17]Davies L,Fassbender K,Walter S.Sphingolipids in Neuroinflammation[M].Berlin:Springer Vienna,2013.
[18]Zheng W J,Kollmeyer J,Symolon H,et al.Ceramides and other bioactive sphingolipid backbones in health and disease:Lipidomic analysis,metabolism and roles in membrane structure,dynamics,signaling and autophagy[J].Biochim Biophys Acta,2006,1758(12):1864-1884.
[19]Khan M,Ekhon B K,Sekhon C S,et al.Sphingolipids in rat model of transient focal cerebral ischemia:Implication for stroke injury[J].J Neurochem,2008,81(S1):108-111.
[20]Novgorodov S A,Gudz T I.Ceramide and mitochondria in ischemic brain injury[J].Int J Biochem Mol Biol,2011,2(4):347-361.