目的 探討姜黃素（CUR）對非酒精性脂肪肝?。∟AFLD）的代謝調(diào)節(jié)作用。方法 小鼠適應(yīng)性飼養(yǎng)3 d后，隨機(jī)分為3組：對照（C）組、高脂飲食模型（HFD）組、CUR （50 mg/kg）組。C組飼喂普通飼料，HFD和CUR組飼喂高脂飼料，CUR同時(shí)ig給藥10周，C組和HFD組ig給予0.5% CMC-Na溶液，給藥體積均為10 mL/kg。給藥結(jié)束后，取血和肝臟，肝組織切片后進(jìn)行HE染色和油紅O染色，光學(xué)顯微鏡觀察病理變化；采用基于氣相色譜-質(zhì)譜聯(lián)用（GC/MS）的代謝組學(xué)方法檢測血清和肝臟組織樣品，數(shù)據(jù)通過Simca-P13.0及Metaboanalysis網(wǎng)絡(luò)工具進(jìn)行分析，找出代謝組變化趨勢和相關(guān)差異化合物。此外，制備小鼠肝原代細(xì)胞，棕櫚酸（PA）100 mmol/L誘導(dǎo)細(xì)胞NAFLD體外模型，觀察CUR （10 μmol/L）對代謝組變化的影響。結(jié)果 油紅O染色結(jié)果顯示，HFD小鼠肝臟組織存在大量紅染油滴，CUR組小鼠肝臟組織中的脂質(zhì)油滴明顯減少。HE染色分析顯示，與C組比較，HFD組小鼠肝臟組織有空泡狀，CUR組小鼠肝臟組織與C組比較沒有明顯區(qū)別。對血清樣和肝組織樣品的GC-MS數(shù)據(jù)進(jìn)行PLS-DA分析發(fā)現(xiàn)C組與HFD組偏離較遠(yuǎn)，而CUR組與HFD組相比出現(xiàn)向C組偏移的趨勢，進(jìn)一步S-plot分析發(fā)現(xiàn)影響較大的代謝為膽固醇的合成、酮體的生成以及氨基酸代謝，細(xì)胞實(shí)驗(yàn)得到了類似的結(jié)果；經(jīng)通路MetPA分析和代謝產(chǎn)物富集，血清和細(xì)胞中各組間差異化合物代謝主要集中在氨基酸代謝，肝臟中代謝差異主要集中在氨基酸代謝和部分脂質(zhì)代謝通路；進(jìn)一步進(jìn)行差異代謝物的篩選，HFD組生糖氨基酸和生酮氨基酸較對照組均有不同程度的升高，CUR能夠降低這些氨基酸的水平。結(jié)論 高脂飲食會(huì)造成小鼠三大代謝的異常，姜黃素能夠一定程度上改善小鼠代謝紊亂。

Objective To investigate the metabolic regulation of curcumin (CUR) on mice with nonalcoholic fatty liver disease (NAFLD).Methods After 3 days of adaptive feeding,mice were randomly divided into three groups:control group (C),high fat diet model (HFD) group and CUR (50 mg/kg) group.Group C was fed with common diet,group HFD and CRU were fed with high-fat diet,and Ig was given for 10 weeks.Group C and HFD were given 0.5% CMC-Na solution,the volume of administration was 10 mL/kg.After administration,blood and liver were taken,liver tissue sections were stained with HE and oil red O,and pathological changes were observed by optical microscopy.Serum and liver tissue samples were detected by metabolomics method based on gas chromatography-mass spectrometry (GC/MS).The data were analyzed by Simca-P13.0 and Metaboanalysis network tools to find the trend of metabolome changes and related differential compounds.In addition,primary hepatocytes of mice were prepared and NAFLD was induced by palmitic acid (PA)100 mmol/L in vitro.The effects of CUR (10 micromol/L) on metabolites were observed.Results Oil red O staining results showed that there were a large number of red oil droplets in liver tissue of HFD mice,and lipid oil droplets in liver tissue of CUR mice were significantly reduced.HE staining analysis showed that there were vacuoles in the liver tissue of HFD mice compared with group C,and there was no significant difference between the liver tissue of CUR mice and that of group C.PLS-DA analysis of GC-MS data of serum and liver tissue samples showed that group C deviated from group HFD,while group CUR deviated from group C.Further S-plot analysis showed that cholesterol synthesis,ketone body formation and amino acid metabolism were the most influential metabolites.Similar results were obtained in cell experiments through pathway MetPA analysis and metabolite enrichment.The metabolic differences between groups in serum and cells were mainly concentrated in amino acid metabolism,while those in liver were mainly concentrated in amino acid metabolism and some lipid metabolism pathways.Further screening of different metabolites showed that the levels of sugar-producing amino acids and ketogenic amino acids in HFD group were higher than those in control group,and CUR could reduce the levels of these amino acids.Conclusion High fat diet can cause three major metabolic abnormalities in mice,curcumin can improve the metabolic disorders in mice to a certain extent.

國家自然科學(xué)基金面上項(xiàng)目（81673679）