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脂肪酸代谢在肾脏疾病中的作用及中药干预研究进展

郑志茹, 张尊建, 许风国, 张培

郑志茹, 张尊建, 许风国, 张培. 脂肪酸代谢在肾脏疾病中的作用及中药干预研究进展[J]. 中国药科大学学报, 2023, 54(5): 527-535. DOI: 10.11665/j.issn.1000-5048.2023042801
引用本文: 郑志茹, 张尊建, 许风国, 张培. 脂肪酸代谢在肾脏疾病中的作用及中药干预研究进展[J]. 中国药科大学学报, 2023, 54(5): 527-535. DOI: 10.11665/j.issn.1000-5048.2023042801
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ZHENG Zhiru, ZHANG Zunjian, XU Fengguo, ZHANG Pei. Role of fatty acid metabolism in kidney disease and therapeutic intervention by traditional Chinese medicine[J]. Journal of China Pharmaceutical University, 2023, 54(5): 527-535. DOI: 10.11665/j.issn.1000-5048.2023042801
Citation: ZHENG Zhiru, ZHANG Zunjian, XU Fengguo, ZHANG Pei. Role of fatty acid metabolism in kidney disease and therapeutic intervention by traditional Chinese medicine[J]. Journal of China Pharmaceutical University, 2023, 54(5): 527-535. DOI: 10.11665/j.issn.1000-5048.2023042801
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脂肪酸代谢在肾脏疾病中的作用及中药干预研究进展

  • 中国药科大学药物质量与安全预警教育部重点实验室，南京 210009

基金项目: 国家自然科学基金资助项目（No.82073812，No.82104117，No.82173947，No.82273896）；江苏省自然科学基金资助项目（No.BK20210427）

Role of fatty acid metabolism in kidney disease and therapeutic intervention by traditional Chinese medicine

  • Ministry of Education Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Nanjing 210009, China

Funds: This study was supported by the National Natural Science Foundation of China (No. 82073812, No.82104117, No.82173947, No.82273896) and the Natural Science Foundation of Jiangsu Province (No. BK20210427)

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    摘要
  • 摘要: 脂肪酸代谢主要包括脂肪酸氧化（fatty acid oxidation, FAO）和脂肪酸合成，其在信号转导、能量产生及炎症调节等过程均发挥重要作用。急性肾损伤（acute kidney injury, AKI）、慢性肾病（chronic kidney disease, CKD）与肾癌（renal cell carcinoma, RCC）是典型的肾脏疾病，发病机制复杂、易诱发多种并发症且临床尚无特异性干预措施。现有研究揭示，脂肪酸代谢与多种肾脏疾病的发生发展密切相关。文章综述了肾脏中脂肪酸的代谢特征、脂肪酸代谢失调与AKI、CKD及RCC等肾脏疾病的内在关系，总结了靶向脂肪酸代谢通路缓解肾脏疾病的中药及相关活性成分，为深入研究肾脏疾病脂肪酸代谢相关机制、寻找靶向干预手段提供理论参考。
    Abstract: Fatty acid metabolism, including fatty acid oxidation (FAO) and fatty acid synthesis, plays critical roles in signal transduction, energy production and inflammation regulation.Acute kidney injury (AKI), chronic kidney disease (CKD) and renal cell carcinoma (RCC) are typical renal diseases with complex pathogenesis, susceptibility to multiple complications, and still no effective measure for clinical intervention.Current studies reveal that fatty acid metabolism is closely related to the occurrence and development of a variety of kidney diseases.This article reviews the metabolic characteristics of fatty acid in the kidney, the relationship between fatty acid metabolism disorder and renal diseases (i.e., AKI, CKD and RCC), and summarizes traditional Chinese medicines and related active ingredients targeting fatty acid metabolic pathway to alleviate renal diseases, aiming to provide theoretical reference for the in-depth study of mechanisms related to fatty acid metabolism in renal diseases as well as the development of effective interventions.
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    • 参考文献(72)
  • [1] Bharati J, Jha V. Global Kidney Health Atlas: a spotlight on the Asia-Pacific sector[J]. Kidney Res Clin Pract, 2022, 41(1): 22-30.
    [2] Hoste EAJ, Kellum JA, Selby NM, et al. Global epidemiology and outcomes of acute kidney injury[J]. Nat Rev Nephrol, 2018, 14(10): 607-625.
    [3] Pode-Shakked N, Devarajan P. Human stem cell and organoid models to advance acute kidney injury diagnostics and therapeutics[J]. Int J Mol Sci, 2022, 23(13): 7211.
    [4] GBD Chronic Kidney Disease Collaboration. Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017[J]. Lancet, 2020, 395(10225): 709-733.
    [5] Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249.
    [6] Makhov P, Joshi S, Ghatalia P, et al. Resistance to systemic therapies in clear cell renal cell carcinoma: mechanisms and management strategies[J]. Mol Cancer Ther, 2018, 17(7): 1355-1364.
    [7] Kordalewska M, Macioszek S, Wawrzyniak R, et al. Multiplatform metabolomics provides insight into the molecular basis of chronic kidney disease[J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2019, 1117: 49-57.
    [8] Huang HL, van Dullemen LFA, Akhtar MZ, et al. Proteo-metabolomics reveals compensation between ischemic and non-injured contralateral kidneys after reperfusion[J]. Sci Rep, 2018, 8(1): 8539.
    [9] Fornoni A, Merscher S. Lipid metabolism gets in a JAML during kidney disease[J]. Cell Metab, 2020, 32(6): 903-905.
    [10] He WJ, Li QG, Li XX. Acetyl-CoA regulates lipid metabolism and histone acetylation modification in cancer[J]. Biochim Biophys Acta Rev Cancer, 2023, 1878(1): 188837.
    [11] Korbecki J, Bobiński R, Dutka M. Self-regulation of the inflammatory response by peroxisome proliferator-activated receptors[J]. Inflamm Res, 2019, 68(6): 443-458.
    [12] Dorotea D, Koya D, Ha H. Recent insights into SREBP as a direct mediator of kidney fibrosis via lipid-independent pathways[J]. Front Pharmacol, 2020, 11: 265.
    [13] Ferro CJ, Mark PB, Kanbay M, et al. Lipid management in patients with chronic kidney disease[J]. Nat Rev Nephrol, 2018, 14(12): 727-749.
    [14] Ma HJ, Guo XZ, Cui SC, et al. Dephosphorylation of AMP-activated protein kinase exacerbates ischemia/reperfusion-induced acute kidney injury via mitochondrial dysfunction[J]. Kidney Int, 2022, 101(2): 315-330.
    [15] Baek J, He CC, Afshinnia F, et al. Lipidomic approaches to dissect dysregulated lipid metabolism in kidney disease[J]. Nat Rev Nephrol, 2022, 18(1): 38-55.
    [16] Bai LN, Wang YZ, Zhang L, et al. In situ metabolomics of metabolic reprogramming involved in a mouse model of type 2 diabetic kidney disease[J]. Front Physiol, 2021, 12: 779683.
    [17] Wettersten HI, Hakimi AA, Morin D, et al. Grade-dependent metabolic reprogramming in kidney cancer revealed by combined proteomics and metabolomics analysis[J]. Cancer Res, 2015, 75(12): 2541-2552.
    [18] Ronco C, Bellomo R, Kellum JA. Acute kidney injury[J]. Lancet, 2019, 394(10212): 1949-1964.
    [19] See EJ, Jayasinghe K, Glassford N, et al. Long-term risk of adverse outcomes after acute kidney injury: a systematic review and meta-analysis of cohort studies using consensus definitions of exposure[J]. Kidney Int, 2019, 95(1): 160-172.
    [20] Sun JC, Shannon M, Ando Y, et al. Serum metabolomic profiles from patients with acute kidney injury: a pilot study[J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2012, 893/894: 107-113.
    [21] Ezaki T, Nishiumi S, Azuma T, et al. Metabolomics for the early detection of cisplatin-induced nephrotoxicity[J]. Toxicol Res (Camb), 2017, 6(6): 843-853.
    [22] Zhang P, Chen JQ, Huang WQ, et al. Renal medulla is more sensitive to cisplatin than cortex revealed by untargeted mass spectrometry-based metabolomics in rats[J]. Sci Rep, 2017, 7: 44804.
    [23] Jiang RQ, Jiao Y, Zhang P, et al. Twin derivatization strategy for high-coverage quantification of free fatty acids by liquid chromatography-tandem mass spectrometry[J]. Anal Chem, 2017, 89(22): 12223-12230.
    [24] Jang HS, Noh MR, Jung EM, et al. Proximal tubule cyclophilin D regulates fatty acid oxidation in cisplatin-induced acute kidney injury[J]. Kidney Int, 2020, 97(2): 327-339.
    [25] Li SY, Wu PF, Yarlagadda P, et al. PPAR alpha ligand protects during cisplatin-induced acute renal failure by preventing inhibition of renal FAO and PDC activity[J]. Am J Physiol Renal Physiol, 2004, 286(3): F572-F580.
    [26] Tan ZK, Guo F, Huang Z, et al. Pharmacological and genetic inhibition of fatty acid-binding protein 4 alleviated cisplatin-induced acute kidney injury[J]. J Cell Mol Med, 2019, 23(9): 6260-6270.
    [27] Li LZ, Tao SB, Guo F, et al. Genetic and pharmacological inhibition of fatty acid-binding protein 4 alleviated inflammation and early fibrosis after toxin induced kidney injury[J]. Int Immunopharmacol, 2021, 96: 107760.
    [28] Levey AS. Defining AKD:the spectrum of AKI, AKD, and CKD[J]. Nephron, 2022, 146(3): 302-305.
    [29] Kalantar-Zadeh K, Jafar TH, Nitsch D, et al. Chronic kidney disease[J]. Lancet, 2021, 398(10302): 786-802.
    [30] Pei GC, Yao Y, Yang Q, et al. Lymphangiogenesis in kidney and lymph node mediates renal inflammation and fibrosis[J]. Sci Adv, 2019, 5(6): eaaw5075.
    [31] Liu HJ, Miao H, Yang JZ, et al. Deciphering the role of lipoproteins and lipid metabolic alterations in ageing and ageing-associated renal fibrosis[J]. Ageing Res Rev, 2023, 85: 101861.
    [32] Kang HM, Ahn SH, Choi P, et al. Defective fatty acid oxidation in renal tubular epithelial cells has a key role in kidney fibrosis development[J]. Nat Med, 2015, 21(1): 37-46.
    [33] Kim HJ, Moradi H, Yuan J, et al. Renal mass reduction results in accumulation of lipids and dysregulation of lipid regulatory proteins in the remnant kidney[J]. Am J Physiol Renal Physiol, 2009, 296(6): F1297-F1306.
    [34] Fontecha-Barriuso M, Lopez-Diaz AM, Guerrero-Mauvecin J, et al. Tubular mitochondrial dysfunction, oxidative stress, and progression of chronic kidney disease[J]. Antioxidants (Basel), 2022, 11(7): 1356.
    [35] Afshinnia F, Rajendiran TM, Soni T, et al. Impaired β-oxidation and altered complex lipid fatty acid partitioning with advancing CKD[J]. J Am Soc Nephrol, 2018, 29(1): 295-306.
    [36] Soumura M, Kume S, Isshiki K, et al. Oleate and eicosapentaenoic acid attenuate palmitate-induced inflammation and apoptosis in renal proximal tubular cell[J]. Biochem Biophys Res Commun, 2010, 402(2): 265-271.
    [37] He WJ, Li CW, Huang ZJ, et al. Association of mitochondrial DNA copy number with risk of progression of kidney disease[J]. Clin J Am Soc Nephrol, 2022, 17(7): 966-975.
    [38] Zhan M, Usman IM, Sun L, et al. Disruption of renal tubular mitochondrial quality control by Myo-inositol oxygenase in diabetic kidney disease[J]. J Am Soc Nephrol, 2015, 26(6): 1304-1321.
    [39] Boor P, Celec P, Martin IV, et al. The peroxisome proliferator-activated receptor-α agonist, BAY PP1, attenuates renal fibrosis in rats[J]. Kidney Int, 2011, 80(11): 1182-1197.
    [40] Chung KW, Ha S, Kim SM, et al. PPARα/β activation alleviates age-associated renal fibrosis in sprague dawley rats[J]. J Gerontol A Biol Sci Med Sci, 2020, 75(3): 452-458.
    [41] Ji LN, Song WH, Fang H, et al. Efficacy and safety of chiglitazar, a novel peroxisome proliferator-activated receptor pan-agonist, in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, phase 3 trial (CMAP)[J]. Sci Bull (Beijing), 2021, 66(15): 1571-1580.
    [42] Khuchua Z, Glukhov AI, Strauss AW, et al. Elucidating the beneficial role of PPAR agonists in cardiac diseases[J]. Int J Mol Sci, 2018, 19(11): 3464.
    [43] Zheng RS, Zhang SW, Sun KX, et al. Cancer statistics in China, 2016 [J]. Chin J Oncol (中华肿瘤杂志), 2023, 45(3): 212-220.
    [44] Chakraborty S, Balan M, Sabarwal A, et al. Metabolic reprogramming in renal cancer: events of a metabolic disease[J]. Biochim Biophys Acta Rev Cancer, 2021, 1876(1): 188559.
    [45] Rixidan·Aimaiti, Ainiwaer·Aimudula, Aikebaier·Ainiwaer, et al. Expression of PPARα in renal clear cell carcinoma and its relationship with prognosis[J]. J Mod Oncol (现代肿瘤医学), 2022, 30(7): 1238-1243.
    [46] Wang R, Zhao J, Jin JC, et al. WY-14643 attenuates lipid deposition via activation of the PPARα/CPT1A axis by targeting Gly335 to inhibit cell proliferation and migration in ccRCC[J]. Lipids Health Dis, 2022, 21(1): 121.
    [47] Abu Aboud O, Donohoe D, Bultman S, et al. PPARα inhibition modulates multiple reprogrammed metabolic pathways in kidney cancer and attenuates tumor growth[J]. Am J Physiol Cell Physiol, 2015, 308(11): C890-C898.
    [48] Qiu B, Ackerman D, Sanchez DJ, et al. HIF2α-dependent lipid storage promotes endoplasmic reticulum homeostasis in clear-cell renal cell carcinoma[J]. Cancer Discov, 2015, 5(6): 652-667.
    [49] von Roemeling CA, Marlow LA, Wei JJ, et al. Stearoyl-CoA desaturase 1 is a novel molecular therapeutic target for clear cell renal cell carcinoma[J]. Clin Cancer Res, 2013, 19(9): 2368-2380.
    [50] Horiguchi A, Asano T, Asano T, et al. Fatty acid synthase over expression is an indicator of tumor aggressiveness and poor prognosis in renal cell carcinoma[J]. J Urol, 2008, 180(3): 1137-1140.
    [51] Shen S, Wang JF, Wu JQ, et al. GC/MS-based metabolomic analysis of alleviated renal ischemia-reperfusion injury induced by remote ischemic preconditioning[J]. Eur Rev Med Pharmacol Sci, 2017, 21(4): 765-774.
    [52] Lim YJ, Tonial NC, Hartjes ED, et al. Metabolomics for the identification of early biomarkers of nephrotoxicity in a mouse model of cisplatin-induced acute kidney injury[J]. Biomed Pharmacother, 2023, 163: 114787.
    [53] Chen H, Chen L, Liu D, et al. Combined clinical phenotype and lipidomic analysis reveals the impact of chronic kidney disease on lipid metabolism[J]. J Proteome Res, 2017, 16(4): 1566-1578.
    [54] Tan SK, Welford SM. Lipid in renal carcinoma: queen bee to target [J]? Trends Cancer, 2020, 6(6): 448-450.
    [55] Jing L, Guigonis JM, Borchiellini D, et al. LC-MS based metabolomic profiling for renal cell carcinoma histologic subtypes[J]. Sci Rep, 2019, 9(1): 15635.
    [56] Wang QF, Zhang W, Qi XC, et al. The mechanism of liver X receptor regulates the balance of glycoFAsynthesis and cholesterol synthesis in clear cell renal cell carcinoma[J]. Clin Transl Med, 2023, 13(5): e1248.
    [57] van der Mijn JC, Fu LP, Khani F, et al. Combined metabolomics and genome-wide transcriptomics analyses show multiple HIF1α-induced changes in lipid metabolism in early stage clear cell renal cell carcinoma[J]. Transl Oncol, 2020, 13(2): 177-185.
    [58] Li SS, Xiao X, Han L, et al. Renoprotective effect of Zhenwu Decoction against renal fibrosis by regulation of oxidative damage and energy metabolism disorder[J]. Sci Rep, 2018, 8(1): 14627.
    [59] Zhao J, Tostivint I, Xu LD, et al. Efficacy of combined Abelmoschus manihot and irbesartan for reduction of albuminuria in patients with type 2 diabetes and diabetic kidney disease: a multicenter randomized double-blind parallel controlled clinical trial[J]. Diabetes Care, 2022, 45(7): e113-e115.
    [60] Li WX, Lei Y, Li MY, et al. Mechanism of Huangkui Capsule in treatment of diabetic nephropathy based on literature mining and network pharmacology[J]. Drug Eval Res(药物评价研究), 2021, 44(10): 2214-2224.
    [61] Zhang ZH, Vaziri ND, Wei F, et al. An integrated lipidomics and metabolomics reveal nephroprotective effect and biochemical mechanism of Rheum officinale in chronic renal failure[J]. Sci Rep, 2016, 6: 22151.
    [62] Zhao YY, Lei P, Chen DQ, et al. Renal metabolic profiling of early renal injury and renoprotective effects of Poria cocos epidermis using UPLC Q-TOF/HSMS/MSE[J]. J Pharm Biomed Anal, 2013, 81/82: 202-209.
    [63] Song YQ, Hu TT, Gao H, et al. Altered metabolic profiles and biomarkers associated with astragaloside IV-mediated protection against cisplatin-induced acute kidney injury in rats: an HPLC-TOF/MS-based untargeted metabolomics study[J]. Biochem Pharmacol, 2021, 183: 114299.
    [64] Xu L, Zhang YX, Zhang P, et al. Integrated metabolomics and network pharmacology strategy-driven active traditional Chinese medicine ingredients discovery for the alleviation of cisplatin nephrotoxicity[J]. Chem Res Toxicol, 2019, 32(12): 2411-2421.
    [65] Liu P, Wang C, Wang Y, et al. Zishen Qingre Tongluo formula improves renal fatty acid oxidation and alleviated fibrosis via the regulation of the TGF-β1/Smad3 signaling pathway in hyperuricemic nephrology rats[J]. Biomed Res Int, 2021, 2021: 2793823.
    [66] Song XR, Du ZS, Yao ZQ, et al. Rhein improves renal fibrosis by restoring Cpt1a-mediated fatty acid oxidation through SirT1/STAT3/twist1 pathway[J]. Molecules, 2022, 27(7): 2344.
    [67] Liu LM, Ning XX, Wei L, et al. Twist1 downregulation of PGC-1α decreases fatty acid oxidation in tubular epithelial cells, leading to kidney fibrosis[J]. Theranostics, 2022, 12(8): 3758-3775.
    [68] Li Y, Ye X. Experimental study on regulation effects of Panax polysaccharides on inflammation and dyslipidemia in diabetic nephropathy rats[J]. Chin J Tradit Med Sci Technol(中国中医药科技), 2018, 25(1): 43-47.
    [69] Koh ES, Lim JH, Kim MY, et al. Anthocyanin-rich Seoritae extract ameliorates renal lipotoxicity via activation of AMP-activated protein kinase in diabetic mice[J]. J Transl Med, 2015, 13: 203.
    [70] Liang XY, Yang YF, Huang ZG, et al. Panax notoginseng saponins mitigate cisplatin induced nephrotoxicity by inducing mitophagy via HIF-1α[J]. Oncotarget, 2017, 8(61): 102989-103003.
    [71] Yu XW, Meng X, Xu M, et al. Celastrol ameliorates cisplatin nephrotoxicity by inhibiting NF-κB and improving mitochondrial function[J]. EBioMedicine, 2018, 36: 266-280.
    [72] Qin X, Jiang M, Zhao Y, et al. Berberine protects against diabetic kidney disease via promoting PGC-1α-regulated mitochondrial energy homeostasis[J]. Br J Pharmacol, 2020, 177(16): 3646-3661.
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  • 收稿日期:  2023-04-27
  • 修回日期:  2023-09-03
  • 刊出日期:  2023-10-24

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