摘要
目的:从代谢通路角度阐明护肝片保肝作用的药效及作用机制。方法:将36只雄性SD大鼠随机分成正常组(0.5%羧甲基纤维素钠)、模型组(0.5%羧甲基纤维素钠)和护肝片组(1.7 g/kg),每组12只,每天ig给药1次,连续给药9 d。末次给药后1 h,模型组和护肝片组大鼠ip 50%四氯化碳(CCl_4)花生油溶液1 mL/kg诱导肝损伤。造模24 h后,检测大鼠肝组织中丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)水平;利用核磁共振氢谱(~1H-NMR)代谢组学技术建立大鼠血清和肝代谢物谱,分析护肝片对CCl_4致急性肝损伤大鼠血清和肝代谢轮廓变化和潜在生物标志物的影响。结果:与正常组比较,模型组大鼠肝组织中MDA水平显著升高(P<0.05),SOD、GSH-Px水平显著降低(P<0.05);大鼠机体生理及物质代谢均发生了明显的改变,11种血清代谢潜在生物标志物和14种肝代谢潜在生物标志物水平均显著升高/降低(P<0.05)。与模型组比较,护肝片组大鼠肝组织中MDA水平显著降低(P<0.05),SOD、GSH-Px水平显著升高(P<0.05)。大鼠血清和肝代谢趋于正常,6种血清代谢潜在生物标志物(异亮氨酸、亮氨酸、3-羟基丁酸、丙酮、乙酰乙酸、胆碱)和8种肝代谢潜在生物标志物(3-羟基丁酸、丙氨酸、谷氨酸、丙酮酸、琥珀酸、胆碱、乳酸、葡萄糖)得到显著回调(P<0.05)。结论:护肝片保肝的机制可能与抗氧化应激及调控脂质代谢、糖代谢和氨基酸代谢有关。
OBJECTIVE：To elucidate the efficacy and mechanism of Hugan tablets in hepatoprotective effects from perspective of metabolic pathways. METHODS：36 male rats were randomly divided into normal group（0.5% sodium carboxymethyl cellulose）,model group（0.5%sodium carboxymethyl cellulose）and Hugan tablets group（1.7 g/kg）,12 in each group,intragastrically administrated once a day,for 9 d. After 1 h of last administration,rats in model group and Hugan tablets group were intraperitoneally injected 50%CCl_4 peanut oil solution 1 mL/kg to induce liver injury. After 24 h of modeling,malondialdehyde（MDA）,superoxide dismutase（SOD）,glutathione peroxidase（GSH-Px）levels in liver tissue of rats were detected. Nuclear magnetic resonance spectroscopy（~1H-NMR）metabolomics technique was adopted to establish the serum and liver metabolite profiles of rats,and the effects of Hugan tablets on changes of metabolic profile and potential biomarkers in serum and liver of rats with CCl_4-induced acute liver injury were analyzed. RESULTS：Compared with normal group,MDA level in liver tissue of rats in model group was significantly increased（P0.05）,SOD and GSH-Px levels were significantly reduced（P0.05）. Both body physiology and material metabolism of rats were obviously changed,and levels of 11 metabolic potential biomarkers in serum and 14 metabolic potential biomarkers in liver were significantly increased/decreased（P0.05）. Compared with model group,MDA level in liver tissue in Hugan tablets group was significantly reduced（P0.05）,SOD and GSH-Px levels were significantly increased（P0.05）. Serum and liver metabolism tended to be normal,6 metabolic potential biomarkers（isoleucine,leucine,3-hydroxybutyrate,acetone,acetoacetate,choline） in serum and 8 metabolic potential biomarkers（3-hydroxybutyrate,alanine,glutamate,pyruvate,succinate,choline,lactate,glucose）in liver got significant callback（P0.05）. CONCLUSIONS：The hepatoprotective mechanism of Hugantablets may be associated with antioxidative stress and regulation of lipid metabolism,glucose metabolism and amino acid metabolism.
出处
《中国药房》
CAS
北大核心
2017年第34期4776-4780,共5页
China Pharmacy
基金
国家自然科学基金青年科学基金项目(No.81603397
81403075)
关键词
护肝片
急性肝损伤
代谢组学
核磁共振
潜在生物标志物
大鼠
Hugan tablets
Acute hepatic injury
Metabo-nomics
Nuclear magnetic resonance spectroscopy
Protential biomarkers
Rats
