基于肝脏脂质代谢紊乱的白鲜皮水提液致大鼠肝毒性研究OA
Study on Hepatotoxicity of Dictamni Cortex Water Extract in Rats Based on Liver Lipid Metabolism Disorder
目的:揭示白鲜皮干扰脂质代谢紊乱导致大鼠肝损伤的机制.方法:32 只SPF级SD雄性大鼠随机分成空白组、白鲜皮高剂量组(8.1 g/kg)、白鲜皮中剂量组(2.7 g/kg)、白鲜皮低剂量组(0.9 g/kg),每组8 只,灌胃给药8 周,检测大鼠体质量及肝脏体质量比、肝毒性相关指标观察大鼠肝脏的变化;HE染色与油红O染色法评价肝组织的病理变化及脂滴聚集情况;检测肝组织中AMPK、PPAR-α、IL-1β、TNF-α的mRNA含量;使用高效液相色谱-质谱联用(LC-MS/MS)技术检测大鼠肝脏脂质水平变化,采用多元统计分析筛选其中的差异脂质代谢物.结果:与空白组比较,白鲜皮各剂量组的肝脏体质量比增加(P<0.01,P<0.001),大鼠血清中谷草转氨酶(AST)、谷丙转氨酶(ALT)、白蛋白(ALB)水平显著升高(P<0.05,P<0.001),HE染色与油红O染色表明白鲜皮高剂量组可明显引起大鼠肝脏的脂肪性病变,肝组织中炎症因子IL-1β、TNF-α的mRNA水平显著升高(P<0.01),PPAR-α的mRNA水平显著降低(P<0.01),脂质组学分析发现,与空白组比较,白鲜皮高剂量组有 156 个脂质发生了显著改变,主要有甘油脂类、磷脂酰胆碱类、鞘脂类等,具体表现为PC(16∶0/18∶2)、PC(16∶0/18∶1)、PC(14∶0/18∶2)、PC(15∶0/18∶2)、TG(16∶0/16∶0/16∶0)、TG(18∶0/16∶0/16∶0)、SM(d42∶1)、SM(d42∶2)、SM(d42∶3)等在给药后含量明显变化,表明白鲜皮高剂量组给药后引起了大鼠的肝脏脂质代谢水平紊乱.结论:白鲜皮水提液通过干扰鞘磷脂(SM)、神经酰胺(Cer)、甘油三酯(TG)、磷脂酰胆碱(PC)等脂质代谢引起大鼠肝损伤.
Objective:To explore the mechanism of liver injury induced by Dictamni Cortex water extract through interference with lipid metabolism in the liver.Methods:Thirty-two SPF-grade male SD rats were randomly divided into four groups:control group,high-dose Dictamni Cortex group(8.1 g/kg),medium-dose group(2.7 g/kg),and low-dose group(0.9 g/kg),with 8 rats in each group.The rats were administered by gavage for 8 weeks.Liver weight,liver-to-body weight ratio,and liver toxicity-related indicators were measured to observe changes in the rats·liver.Hematoxylin-eosin(HE)staining and Oil Red O staining were used to assess the pathological changes and lipid droplet accumulation in liver tissues.The mRNA levels of AMPK,PPAR-α,IL-1β,and TNF-α were detected in liver tissues.Lipid levels in the liver were analyzed by LC-MS/MS,and multivariate statistical analysis was used to identify differentially expressed lipid metabolites.Results:Compared with the control group,the liver-to-body weight ratio was increased in all Dictamni Cortex dose groups(P<0.01,P<0.001).In the high-dose group,AST、ALT、ALB levels were significantly increased(P<0.05,P<0.001).HE and Oil Red O staining showed that the high-dose group significantly induced fatty liver lesions in rats.The mRNA levels of inflammatory factors IL-1β and TNF-α were significantly increased(P<0.01),while the mRNA levels of PPAR-α,were significantly reduced(P<0.01).Lipidomics analysis showed that,compared to the control group,156 lipid species were significantly altered in the high-dose group,including glycerolipids,phosphatidylcholine,sphingolipids,etc.Specific lipids such as PC(16:0/18:2),PC(16:0/18:1)、PC(14:0/18:2)、PC(15:0/18:2)、TG(16:0/16:0/16:0),TG(18:0/16:0/16:0)、SM(d42:1),SM(d42:2),SM(d42:3)showed significantly variation levels after treatment.These results suggest that the high-dose Dictamni Cortex water extract disturbed lipid metabolism in the liver of rats.Conclusion:The water extract of Dictamni Cortex induces liver injury in rats by interfering with lipid metabolism,particularly sphingolipids(SM),ceramides(Cer),triglycerides(TG),and phosphatidylcholine(PC).
高蕊;卢芳;孙慧娟;张萌萌;邓戈宇;黄琳;刘树民
黑龙江中医药大学,黑龙江 哈尔滨 150040黑龙江中医药大学,黑龙江 哈尔滨 150040黑龙江中医药大学,黑龙江 哈尔滨 150040黑龙江中医药大学,黑龙江 哈尔滨 150040黑龙江中医药大学,黑龙江 哈尔滨 150040黑龙江中医药大学,黑龙江 哈尔滨 150040黑龙江中医药大学,黑龙江 哈尔滨 150040
医药卫生
白鲜皮脂质组学肝损伤
Dictamni CortexLipidomicsLiver injury
《中医药学报》 2026 (1)
26-32,7
国家重点研发计划-中医药现代化(2022YFC3502100,2022YFC3502102,2022YFC3502102-04)
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