首页|基于脂质代谢组学研究羟基红花黄色素A治疗高脂血症LDLR-/-小鼠的作用机制

基于脂质代谢组学研究羟基红花黄色素A治疗高脂血症LDLR-/-小鼠的作用机制

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[目的]基于脂质代谢组学方法考察羟基红花黄色素A(HSYA)对高脂饲料诱导的LDLR-/-小鼠高脂血症脂质代谢的影响及其机制.[方法]将28只雄性LDLR-/-小鼠分为对照组与高脂组.对照组喂养普通饲料,高脂组喂养高脂饲料,6 周后,高脂组按照血清中低密度脂蛋白胆固醇(LDL-C)含量平均分为 4 组:模型组、辛伐他汀组、HSYA(3.8 mg/kg)低剂量组、HSYA(7.6 mg/kg)高剂量组.给药11周,给药期间同时给予高脂饲料饲养.全自动生化仪检测小鼠血清中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、三酰甘油(TG)、总胆固醇(TC)、LDL-C含量,苏木精-伊红(HE)染色观察肝组织病理形态,油红O染色观察小鼠肝脏组织脂肪蓄积情况,采用靶向脂质组学技术对LDLR-/-小鼠血清中脂质进行测定.[结果]与对照组比较,模型组小鼠血清中LDL-C、TC、TG、AST、ALT含量升高(P<0.05),肝组织出现大小不等的脂滴浸润,肝细胞排列紊乱,大量脂质蓄积.与模型组比较,HSYA两组小鼠血清中LDL-C、TC、TG、AST、ALT含量降低(P<0.05),肝脏的脂肪变性、脂质蓄积等病理情况得到改善.脂质组学检测结果显示,模型组和对照组之间具有差异的脂质分子共有 14 种(VIP>1,P<0.05).HSYA两组与模型组比较,17 种脂质分子呈现相反的趋势并具有差异,分别为PE(18∶0/18∶1)、PE(18∶0/18∶2)、PE(18∶0/20∶3)、PE(18∶0/20∶4)、PE(O-18∶0/18∶1)、PE(O-18∶0/20∶4)、LPE(18∶1)、LPE(20∶4)、FFA(22∶4)、PI(18∶0/18∶2)、PI(16∶0/18∶1)、PI(18∶1/18∶1)、LPI(18∶0)、PG(18∶1/16∶1)、PG(18∶1/18∶1)、PG(18∶1/18∶2)、PA(18∶1/18∶1)(VIP>1,P<0.05).[结论]研究利用脂质组学技术,发现HSYA可以通过调节高脂血症LDLR-/-小鼠血清中脂质代谢水平,发挥治疗高脂血症的作用,为临床应用HSYA提供了新的参考依据.
To investigate the mechanism of Hydroxysafflor yellow A in the treatment of hyperlipidemia in LDLR-/-mice based on lipid metabolomics
[Objective]To investigate the effect and mechanism of Hydroxysafflor yellow A(HSYA)on lipid metabolism in LDLR-/-mice with hyperlipidemia induced by high-fat diet based on lipid metabolomics.[Methods]Twenty-eight male LDLR-/-mice were divided into control group and high-fat diet group.The control group was fed with normal diet,and the high-fat group was fed with high-fat diet.After 6 weeks,according to the content of LDL-C,the mice were divided into four groups[model group,simvastatin group,low dose HSYA(3.8 mg/kg)and high dose HSYA(7.6 mg/kg)].The drug was administered for 11 weeks,and high-fat diet was given simultaneously during the drug administration.The content of alanine aminotransferase(ALT),aspartate aminotransferase(AST),triglyceride(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)in serum of mice were detected by automatic biochemical instrument,the pathological morphology of liver histology was observed by hematoxylin-eosin staining,and the fat deposition of liver tissues of mice was observed by oil red O staining,and lipids in the serum of LDLR-/-mice were measured by targeted lipidomic technology.[Results]Compared with the control group,the serum content of LDL-C,TC,TG,AST and ALT in the model group were increased(P<0.05).The liver tissue showed infiltration of lipid droplets of different sizes,disorderly arrangement of hepatocytes,and a large number of lipid deposits.Compared with the model group,the serum content of LDL-C,TC,TG,AST and ALT in the HSYA group were decreased(P<0.05),liver steatosis,lipid deposition and other pathological conditions were improved.The results of lipid profiling showed that there were 14 different lipid molecules(VIP>1,P<0.05).Compared with the model group,17 lipid molecules in the HSYA group showed the opposite trend and had differences,Respectively PE(18∶0/18∶1),PE(18∶0/18∶2),PE(18∶0/20∶3),PE(18∶0/20∶4),PE(O-18∶0/18∶1),PE(O-18∶0/20∶4),LPE(18∶1),LPE(20∶4),FFA(22∶4),PI(18∶0/18∶2),PI(16∶0/18∶1),PI(18∶1/18∶1),LPI(18∶0),PG(18∶1/16∶1),PG(18∶1/18∶1),PG(18∶1/18∶2),PA(18∶1/18∶1)(VIP>1,P<0.05).[Conclusion]Using lipidomics technology,this study found that HSYA could play a role in the treatment of hyperlipidemia by regulating lipid metabolism in the serum of hyperlipidemia LDLR-/-mice,and provided a new reference for its clinical application.

Hydroxysafflor yellow Ahyperlipidemialipidomicsmetabolism of lipid

唐华靖、罗雅歌、杨磊、徐宝欣、徐静雅、苗琳、柴丽娟、张晗、王怡、毛浩萍

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天津中医药大学方剂学教育部重点实验室,天津 301617

悦康药业集团股份有限公司,北京 100176

羟基红花黄色素A 高脂血症 脂质组学 脂代谢

2024

天津中医药大学学报
天津中医药大学

天津中医药大学学报

CSTPCD
影响因子:1.324
ISSN:1673-9043
年,卷(期):2024.43(1)
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