基于生物信息学的肝纤维化血浆代谢组学分析
1. 广西中医药大学, 赛恩斯新医药学院医学系, 广西南宁 530222
2. 广西中医药大学, 壮医药学院, 广西南宁 530222
| 摘 要： | 目的：基于文献计量学探讨肝纤维化代谢产物产物及其相互作用，寻找肝纤维化生物标志物和治疗靶点。方法：联合中文和英文数据库，搜集肝纤维化血浆代谢组学研究。收集纳入研究重复出现的代谢产物作为肝纤维化代谢产物谱，在代谢相关数据库上对代谢产物进行分析处理。结果：共纳入16篇文章，选择了重复出现的24个代谢产物作为肝纤维化的代谢产物谱，它们出现在24条代谢通路上。在MetPA数据库上对其进行通路的拓扑分析，发现氨酰tRNA合成、缬氨酸，亮氨酸和异亮氨酸的生物合成、甘氨酸，丝氨酸和苏氨酸的代谢、苯丙氨酸，酪氨酸和色氨酸的生物合成、鞘脂代谢、苯丙氨酸代谢、精氨酸和脯氨酸代谢、胆汁酸生物合成、糖酵解/糖异生代谢路径与肝纤维化相关。缬氨酸和精氨酸以及亮氨酸出现的次数大于5次。结论：肝纤维化的病理机制涉及氨基酸、蛋白质、脂类、糖类、胆汁酸的生物代谢，缬氨酸和精氨酸以及亮氨酸可以作为肝纤维化的生物标志物。 |
| 关 键 词： | 肝纤维化; 代谢产物; 标志物; 生物信息学 |
| DOI： | 10.57237/j.mrf.2023.01.004 |
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收稿日期: 2023-02-24
接受日期: 2023-04-12
在线出版日期: 2023-04-25
Analysis of Plasma Metabolomics of Liver Fibrosis Based on Bioinformatics
1. Department of Medicine, Faculty of Chinese Medicine Science, Guangxi University of Chinese Medicine, Nanning 530222, China
2. Zhuang Medical College, Guangxi University of Chinese Medicine, Nanning 530222, China
| Abstract: | Objective: To explore the metabolites of liver fibrosis and their interactions based on bibliometrics, and to find biomarkers and therapeutic targets for liver fibrosis. Methods: Combined Chinese and English databases were used to collect plasma metabolomics studies of liver fibrosis. Recurring metabolites from the included studies were collected as liver fibrosis metabolite profiles, and metabolites were analyzed and processed on metabolism-related databases. Results: A total of 16 articles were included, and 24 recurring metabolites were selected as the metabolite spectrum of liver fibrosis, and they appeared in 24 metabolic pathways. Topological analysis of the pathways on the MetPA database revealed that aminyl tRNA synthesis, valine, leucine and isoleucine biosynthesis, glycine, serine and threonine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, sphingolipid metabolism, phenylalanine metabolism, arginine and proline metabolism, bile acid biosynthesis, and glycolytic/glycoisogenic metabolic pathways were associated with liver fibrosis. Valine, arginine and leucine occur more than 5 times. Conclusion: The pathological mechanism of liver fibrosis involves the biological metabolism of amino acids, proteins, lipids, carbohydrates, and bile acids. Valine, arginine and leucine can be used as biomarkersof liver fibrosis. |
| Keywords: | Liver Fibrosis; Metabolites; Markers; Bioinformatics |
参考文献
| [1] | Parola M, Pinzani M. Liver fibrosis: Pathophysiology, pathogenetic targets and clinical issues. Mol Aspects Med. 2019; 65: 37-55. |
| [2] | Baglieri J, Brenner DA, Kisseleva T. The Role of Fibrosis and Liver-Associated Fibroblasts in the Pathogenesis of Hepatocellular Carcinoma. Int J Mol Sci. 2019; 20 (7): 1723. |
| [3] | Tsochatzis EA, Bosch J, Burroughs AK. Future treatments of cirrhosis. Expert Rev Gastroenterol Hepatol. 2014; 8 (5): 571-81. |
| [4] | Li C, Li R, Zhang W. Progress in non-invasive detection of liver fibrosis. Cancer Biol Med. 2018; 15 (2): 124-136. |
| [5] | Wu L, Shen Y, Li F. Non-invasive diagnosis of liver fibrosis: A review of current imaging modalities. Gastroenterol Hepatol. 2020; 43 (4): 211-221. |
| [6] | 杨妮, 徐建良, 盛国光, 肖明中. 代谢组学在中药抗肝纤维化研究中的进展 [J]. 中国医药导报, 2020, 17 (29): 33-36. |
| [7] | 杜桂芳, 董金珂, 张婷, 杨新瑞, 卢姗姗, 曲建慧, 陆荫英, 洪智贤. Fyn与小鼠肝纤维化模型中胆汁酸代谢组分的相关性研究 [J]. 传染病信息, 2018, 31 (4): 326-330. |
| [8] | 仰贤莉, 李光伟, 康璐, 章弘扬, 徐列明, 胡坪. 扶正化瘀方抗大鼠肝纤维化疗效的代谢组学研究 [J]. 中成药, 2016, 38 (11): 2342-2346. |
| [9] | 高国瑗, 郑希元, 彭渊, 陶艳艳, 刘平, 杨涛, 刘成海.扶正化瘀胶囊对二甲基亚硝胺诱导的肝纤维化大鼠血清代谢组学的影响 [J]. 中国中药杂志, 2016, 41 (9): 1725-1731. |
| [10] | 涂灿, 何琴, 周元园, 王肖辉, 张乐, 卫璐戈, 牛明, 逄瑜, 肖小河, 王伽伯. 基于代谢组学的大黄对正常和肝纤维化大鼠双向作用对比研究 [J]. 药学学报, 2018, 53 (7): 1139-1147. |
| [11] | 刘旭文. 基于肝脏代谢组学和网络药理学的岩黄连抗肝纤维化作用机制研究 [D]. 南宁: 广西医科大学, 2019. |
| [12] | 张丹. 基于高效液相色谱-质谱联用技术的HBV相关性肝纤维化血清代谢标志物筛选研究 [D]. 泸州: 西南医科大学, 2020. |
| [13] | 常虹, 白万富, 李倩, 刘全礼, 孟洪宇, 石松利.基于血清生物标志物变化的蒙古扁桃石油醚提取物防治肝纤维疾病进展动态研究 [J]. 中草药, 2021, 52 (1): 108-117. |
| [14] | 张宁, 方衡, 王雪, 张春胜, 刘斌, 赵旭, 耿放.逍遥散对实验性肝纤维化大鼠模型干预作用的代谢组学研究 [J]. 药物分析杂志, 2014, 34 (4): 588-594. |
| [15] | 麻莉. 雄芍汤干预DMN诱导大鼠肝纤维化的代谢组学研究 [D]. 武汉: 湖北中医药大学, 2015. |
| [16] | 唐超玲. 岩黄连指纹图谱及其抗肝纤维化的血清代谢组学研究 [D]. 南宁: 广西医科大学, 2017. |
| [17] | Li Y, Xue H, Fang S, Wang G, Wang Y, Wang T, Shi R, Wu J, Ma Y. Time-series metabolomics insights into the progressive characteristics of 3, 5-diethoxycarbonyl-1, 4-dihydrocollidine-induced cholestatic liver fibrosis in mice. J Pharm Biomed Anal. 2021; 198: 113986. |
| [18] | Chang H, Meng HY, Liu SM, Wang Y, Yang XX, Lu F, Wang HY. Identification of key metabolic changes during liver fibrosis progression in rats using a urine and serum metabolomics approach. Sci Rep. 2017; 7 (1): 11433. |
| [19] | Zhang Y, Zhao M, Liu Y, Liu T, Zhao C, Wang M. Investigation of the therapeutic effect of Yinchen Wuling Powder on CCl4-induced hepatic fibrosis in rats by 1H NMR and MS-based metabolomics analysis. J Pharm Biomed Anal. 2021; 200: 114073. |
| [20] | Wang D, Li R, Wei S, Gao S, Xu Z, Liu H, Wang R, Li H, Cai H, Wang J, Zhao Y. Metabolomics combined with network pharmacology exploration reveals the modulatory properties of Astragali Radix extract in the treatment of liver fibrosis. Chin Med. 2019; 14: 30. |
| [21] | Zhang Y, Zhou Q, Ding X, Ma J, Tan G. Chemical profile of Swertia mussotii Franch and its potential targets against liver fibrosis revealed by cross-platform metabolomics. J Ethnopharmacol. 2021; 274: 114051. |
| [22] | Song YN, Dong S, Wei B, Liu P, Zhang YY, Su SB. Metabolomic mechanisms of gypenoside against liver fibrosis in rats: An integrative analysis of proteomics and metabolomics data. PLoS One. 2017; 12 (3): e0173598. |
| [23] | 张姣丽, 贾小芳, 尹林, 冯艳玲, 吕建新, 张丽军.免疫性肝纤维化大鼠血浆氨基酸浓度与肝纤维化程度的相关性研究[J].中国生化药物杂志, 2015, 35 (1): 52-56. |
| [24] | 田慧, 师水生, 张舒静, 刘庆彤.缬氨酸对肝纤维化的影响[J]. 中国医疗前沿, 2011, 6 (7): 18-19. |
| [25] | Tajiri K, Shimizu Y. Branched-chain amino acids in liver diseases. World J Gastroenterol. 2013; 19 (43): 7620-7629. |
| [26] | Khedr NF, Khedr EG. Branched chain amino acids supplementation modulates TGF-β1/Smad signaling pathway and interleukins in CCl4 -induced liver fibrosis. Fundam Clin Pharmacol. 2017; 31 (5): 534-545. |
| [27] | Zhao CQ, Chen L, Cai H, Yao WL, Zhou Q, Zhu HM, Gao Y, Liu P, Gou XJ, Zhang H. Classification of Gan Dan Shi Re Pattern and Gan Shen Yin Xu Pattern in Patients with Hepatitis B Cirrhosis Using Metabonomics. Evid Based Complement Alternat Med. 2018; 2697468. |
| [28] | 黄金, 徐庆阳, 陈宁. L-苏氨酸的生产方法及研究进展[J].河南工业大学学报(自然科学版), 2007 (5): 88-92. |
| [29] | 韦卓, 伍新诚, 郑景辉.基于文献计量学的高血压肝阳上亢证病人血浆代谢组学研究[J].中西医结合心脑血管病杂志, 2019, 17 (12): 1765-1772. |
| [30] | 杨一林, 曹铁生, 段云友, 阮骊韬, 陈升, 刘禧, 王泓.肝纤维化门静脉压力改变与血管活性物质关系的实验研究[J].中国医学影像技术, 2005 (1): 6-8. |
| [31] | Hannun YA, Obeid LM. Principles of bioactive lipid signalling: lessons from sphingolipids. Nat Rev Mol Cell Biol. 2008; 9 (2): 139-150. |
| [32] | Mullen TD, Obeid LM. Ceramide and apoptosis: exploring the enigmatic connections between sphingolipid metabolism and programmed cell death. Anticancer Agents Med Chem. 2012; 12 (4): 340-363. |
| [33] | Albeituni S, Stiban J. Roles of Ceramides and Other Sphingolipids in Immune Cell Function and Inflammation. Adv Exp Med Biol. 2019; 1161: 169-191. |
| [34] | Holland WL, Bikman BT, Wang LP, Yuguang G, Sargent KM, Bulchand S, Knotts TA, Shui G, Clegg DJ, Wenk MR, Pagliassotti MJ, Scherer PE, Summers SA. Lipid-induced insulin resistance mediated by the proinflammatory receptor TLR4 requires saturated fatty acid-induced ceramide biosynthesis in mice. J Clin Invest. 2011; 121 (5): 1858-1870. |
| [35] | 王诗洋, 王枭, 徐祖清, 刘悦, 孔繁利.苦杏仁苷通过抑制氧化应激及炎症反应减轻四氯化碳诱导的大鼠肝纤维化作用 [J]. 现代免疫学, 2020, 40 (6): 471-475. |
| [36] | 王清平.苯丙氨酸代谢失调与疾病 [J]. 国外医学: 生理. 病理科学与临床分册, 2001, 21 (6): 451-453. |
| [37] | Panday A, Sahoo MK, Osorio D, Batra S. NADPH oxidases: an overview from structure to innate immunity-associated pathologies. Cell Mol Immunol. 2015; 12 (1): 5-23. |
| [38] | Ma X, Zhang Y, Jiang D, Yang Y, Wu G, Wu Z. Protective Effects of Functional Amino Acids on Apoptosis, Inflammatory Response, and Pulmonary Fibrosis in Lipopolysaccharide-Challenged Mice. J Agric Food Chem. 2019; 67(17): 4915-4922. |
| [39] | Dabos KJ, Parkinson JA, Sadler IH, Plevris JN, Hayes PC.(1)H nuclear magnetic resonance spectroscopy-based metabonomic study in patients with cirrhosis and hepatic encephalopathy. World J Hepatol. 2015; 7 (12): 1701-1707. |
| [40] | eissenborn K, Ahl B, Fischer-Wasels D, van den Hoff J, Hecker H, Burchert W, Köstler H. Correlations between magnetic resonance spectroscopy alterations and cerebral ammonia and glucose metabolism in cirrhotic patients with and without hepatic encephalopathy. Gut. 2007; 56 (12): 1736-1742. |
| [41] | Obayashi Y, Arisaka H, Yoshida S, Mori M, Takahashi M. Proline protects liver from D-galactosamine hepatitis by activating the IL-6/STAT3 survival signaling pathway. Amino Acids. 2012; 43 (6): 2371-2380. |
| [42] | Zhou C, Jia HM, Liu YT, Yu M, Chang X, Ba YM, Zou ZM. Metabolism of glycerophospholipid, bile acid and retinol is correlated with the early outcomes of autoimmune hepatitis. Mol Biosyst. 2016; 12 (5): 1574-1585. |
| [43] | 郑丁, 时昭红, 郭洁, 张书, 刘云, 张曼玲.加味茵陈五苓散对非酒精性脂肪肝模型大鼠miR-34a及糖异生的影响 [J]. 天津中医药, 2021, 38 (4): 511-514. |
| [44] | Saha S, Shalova IN, Biswas SK. Metabolic regulation of macrophage phenotype and function. Immunol Rev. 2017; 280 (1): 102-111. |
| [45] | Torres-Castro I, Arroyo-Camarena ÚD, Martínez-Reyes CP, Gómez-Arauz AY, Dueñas-Andrade Y, Hernández-Ruiz J, Béjar YL, Zaga-Clavellina V, Morales-Montor J, Terrazas LI, Kzhyshkowska J, Escobedo G. Human monocytes and macrophages undergo M1-type inflammatory polarization in response to high levels of glucose. Immunol Lett. 2016; 176: 81-89. |
| [46] | 蓝春花, 陈成英, 蓝利, 王新航, 常升搏小吉, 袁江浪, 孔星星, 陆彩玲, 李习艺, 唐深. 2-DG抑制糖酵解和线粒体自噬调控M1型巨噬细胞极化 [J]. 广西医科大学学报, 2021, 38 (4): 704-709. |
