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四氯化碳诱导大鼠非酒精性脂肪肝的生物标记物研究
Study on the Biomarkers of CCl4 induced Non alcoholic Fatty Liver Disease in Rats
投稿时间:2017-12-20  修订日期:2018-01-16
DOI:
中文关键词:  非酒精性脂肪肝  代谢组学  生物标记物  亚油酸  磷脂酰胆碱
英文关键词:Non alcoholic fatty liver disease  Metabolomics  Biomarker  Linoleic acid  Phosphatidylcholines
基金项目:深圳市知识创新计划基础研究项目(编号:JCYJ20160420103948542)
作者单位
金毅1 黄宝明2* 吕爱贞2 张金龙2 杨雯2 徐愉林2 王茜2 李静2 1.深圳市药品检验研究院 深圳药品质量标准研究重点实验室 广东深圳 518057 2. 广东东阳光药业有限公司 
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中文摘要:
      摘 要 目的:应用代谢组学的方法研究四氯化碳(CCl4)诱导的非酒精性脂肪肝(NAFLD)大鼠模型的血浆代谢产物变化,探讨NAFLD的发病机制,提示该代谢途径中的特异性生物标记物。方法: 将雄性大鼠分成空白对照组、CCl4诱导的模型组、给予具有改善脂类代谢功能的中药配方通络祛浊方的干预组和治疗组,于第9周静脉取血,使用高效液相 四极杆飞行时间质谱(HPLC QTOF/MS)检测到超过2 300个内源性代谢产物,并解剖做病理观察。使用PCA、双聚类及OPLS DA模型筛选潜在的NAFLD的生物标记物,并通过Metaboanalyst对关键的代谢产物进行代谢通路分析。结果:游离脂肪酸(FFA)及磷脂类化合物在模型组相比空白对照组明显减少,干预组或治疗组中部分代谢产物的含量相对于模型组有所回升,甚至恢复至空白对照组水平。亚油酸及磷脂酰胆碱PC(0∶〖KG-*2〗0/18∶〖KG-*2〗0)在空白对照组与模型组间、干预组与模型组间、治疗组与模型组间差异均有统计学意义(P<0.05)。结论:代谢产物亚油酸及磷脂酰胆碱PC(0∶〖KG-*2〗0/18∶〖KG-*2〗0)可能是CCl4诱导的NAFLD的生物标记物。中药通络祛浊方对本模型的干预和治疗均有疗效,能够改善NAFLD大鼠的肝脏脂肪积蓄状况。
英文摘要:
      ABSTRACT Objective: To investigate the changes of plasma metabolites in carbon tetrachloride (CCl4) induced non alcoholic fatty liver disease (NAFLD) rat model by using metabolomics, explore the pathogenesis of NAFLD and study the specific biomarkers in the metabolic pathway. Methods: The male rats were divided into the blank control group, CCl4 induced NAFLD model group, prevention group and treatment group, and the last two groups were given traditional Chinese medicine Tongluo Quzhuo Fang to improve the lipid metabolism. Venous blood was withdrawn in the ninth week and investigated by high performance liquid chromatography quadrupole time of flight mass spectrometry (HPLC QTOF/MS). Over 2300 endogenous metabolites were detected, and the liver tissues were observed pathologically. The potential biomarkers for NAFLD were screened by PCA, bicluster and OPLS DA models, and the metabolic pathways were analyzed by Metaboanalyst. Results: Free fatty acids (FFA) and phospholipids in the model group decreased significantly when compared with that in the blank control group, while the content of some metabolites in both of the prevention group and the treatment group returned to the level of the control group. Linoleic acid and phosphatidylcholine PC (0∶〖KG-*2〗0/18∶〖KG-*2〗0) showed significant difference (P<0.05) between the blank control group and the model group, the model group and the prevention/treatment group. Conclusion:The metabolites linoleic acid and phosphatidylcholine PC (0∶〖KG-*2〗0/18∶〖KG-*2〗0) may be the potential biomarkers of CCl4 induced NAFLD. The intervention and treatment of traditional Chinese medicine Tongluo Quzhuo Fang on the NAFLD model are effective, which can decrease the liver fat accumulation in NAFLD rats.
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