疏肝健脾方对四氯化碳诱导的肝纤维化大鼠肝脏代谢组学的影响  

Effect of Shugan Jianpi Fang(疏肝健脾方) on Liver Metabonomics in Hepatic Fibrosis Rats Induced by Carbon Tetrachloride

作　　者：高家荣[1] 陈金锋[2] 姜辉[1] 韩燕全[1] 

机构地区：[1]安徽中医药大学第一附属医院,安徽省合肥市梅山路117号230031 [2]安徽省六安市中医院

出　　处：《中医杂志》2015年第11期961-966,共6页Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金(81102874)

摘　　要：目的从代谢组学的角度探讨疏肝健脾方防治肝纤维化的可能作用机制。方法 15只SD大鼠随机分为正常组、模型组、疏肝健脾方组,每组5只。模型组和疏肝健脾方组皮下注射50%四氯化碳溶液0.1 ml/100 g,每周2次,连续12周,复制大鼠肝纤维化模型。造模第1天起,疏肝健脾方组给予疏肝健脾方16.2 g/(kg·d)灌胃,正常组和模型组给予等量生理盐水。每天1次,连续16周。末次给药后处死大鼠,取肝组织观察病理学变化,采用气相色谱-飞行时间质谱联用技术分析其代谢谱变化,鉴定差异化合物并进行相关代谢通路分析。结果模型组大鼠肝组织见有少量的脂肪空泡变性,结缔组织增生,炎性细胞浸润,可见非典型的假小叶形成;疏肝健脾方组未见大范围的脂肪空泡,仅有少量炎性细胞浸润,肝纤维化明显好转。与正常组比较,模型组中共发现棕榈酸、二十碳烯酸、苹果酸、延胡索酸、谷氨酰胺、盐德草碱、N-乙酰-4-氨基丁酸、葡萄糖酸8个生物标志物;与模型组比较,疏肝健脾方能够使8个生物标志物向正常水平靠近。结论疏肝健脾方对肝纤维化大鼠有一定的保护作用,其机制可能与调节能量代谢、酪氨酸代谢、脂肪酸代谢、氨基酸代谢、糖代谢紊乱有关。Objective To explore possible mechanism of Shugan Jianpi Fang in preventing and treating hepatic fibrosis by metabonomics method. Methods Fifteen Sprague Dawley rats were randomly divided into normal group （ n = 5 ）, model group （ n = 5 ） and Shugan Jianpi Fang group （ n = 5）. Rats in model gi＇oup and Shugan Jianpi Fang group were given hypodermic injection of 50% carbon tetrachloride solution, 0. 1 ml/lOOg, twice a week, for 12 weeks to replicate rat models with hepatic fibrosis. From the first day of modeling, Shugan Jianpi Fang group was given Shugan Jianpi Fang I6. 2g/ （kg · d） by gavage, and normal group and model group were given equivalent normal saline, once every day, for 16 weeks. Rats were killed after the last administration. Hepatic tissue was taken out to observe the pathological changes. Gas chromatography-time-of-flight mass spectrometry （GC-TOFMS） was adopted to analyze the changes of metabolic profiling. Different compounds were identified and relative metabolic pathways were analyzed. Results In hepatic tissue of rats in model group, there was a little fatty degeneration, connective tissue proliferation, inflammatory cell infiltration, and atypical pseudolobule. Rats＇ hepatic tissue of Shugan Jianpi Fang group showed no large-scale fat vacuole, but a little inflammatory cell infiltration and improved hepatic fibrosis. Compared with normal group, 8 biomarkers including palmitic acid, eicosenoic acid, malic acid, fumaric acid, glutamine, halostachine, N-acetyl-4-amino butyric acid and gluconate were found in model group. Compared with model group, Shugan Jianpi Fang could change 8 biomarkers close to the normal levels. Conclu- sion Shugan Jianpi Fang could provide a certain extent protection to rats with hepatic fibrosis. The mechanism may be related to regulating the disorders of energy, tyrosine, fatty acid, amino acid, and glucose metabolism.

关 键 词：肝纤维化 疏肝健脾方 代谢组学 肝脏代谢谱 气相色谱-飞行时间质谱联用技术 

分 类 号：R285.5[医药卫生—中药学]