药学学报, 2020, 55(12): 2818-2826
引用本文:
陈振山, 张耀文, 王小明, 田振华, 蒋海强, 齐冬梅. 生物钟系统调控机体代谢的分子机制及中药干预研究进展[J]. 药学学报, 2020, 55(12): 2818-2826.
CHEN Zhen-shan, ZHANG Yao-wen, WANG Xiao-ming, TIAN Zhen-hua, JIANG Hai-qiang, QI Dong-mei. The molecular mechanism by which the circadian rhythm regulates body metabolism and research progress on intervention in the circadian rhythm by traditional Chinese medicine[J]. Acta Pharmaceutica Sinica, 2020, 55(12): 2818-2826.

生物钟系统调控机体代谢的分子机制及中药干预研究进展
陈振山1, 张耀文1, 王小明2,3,4, 田振华2,3,4, 蒋海强2,3,4, 齐冬梅2,3,4
1. 山东中医药大学药学院, 山东 济南 250355;
2. 山东中医药大学实验中心, 山东 济南 250355;
3. 山东省中医药基础研究重点实验室, 山东 济南 250355;
4. 山东中医药大学, 教育部中医药经典理论重点实验室, 山东 济南 250355
摘要:
昼夜节律是生物体适应外界环境的昼夜周期性变化的一种内在调控机制,在机体的代谢过程中具有重要的作用,通过参与机体内多个器官的代谢途径来达到调控机体稳态的作用。当饮食时间、作息颠倒、睡眠障碍等外源性因素引起机体的昼夜节律发生紊乱时,机体发生代谢综合征的风险明显提高。本文旨在阐述昼夜节律与机体代谢之间的关系,并总结消化系统、肝脏系统、肾脏系统和胆汁酸的昼夜节律调节分子机制,综述中药干预昼夜节律的研究进展,为后续昼夜节律的中药研究和分子机制研究提供合理的、有价值的参考依据。
关键词:    生物钟      代谢      分子机制      中药     
The molecular mechanism by which the circadian rhythm regulates body metabolism and research progress on intervention in the circadian rhythm by traditional Chinese medicine
CHEN Zhen-shan1, ZHANG Yao-wen1, WANG Xiao-ming2,3,4, TIAN Zhen-hua2,3,4, JIANG Hai-qiang2,3,4, QI Dong-mei2,3,4
1. School of Pharmaceutical Sciences, Shandong University of Traditional Chinese Medicine, Jinan 250355, China;
2. Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan 250355, China;
3. Shandong Provincial Key Laboratory of Traditional Chinese Medicine for Basic Research, Jinan 250355, China;
4. Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
Abstract:
Circadian rhythm is an internal regulatory mechanism that allows organisms to adapt to circadian changes in the external environment, and can regulate the body's steady state by affecting the metabolic pathways of multiple organs. When exogenous factors such as eating time, worktime changes, and sleep disturbances cause the body's circadian rhythm to be disrupted, the risk of developing metabolic syndrome is significantly increased. This article explores the relationship between circadian rhythm and body metabolism and summarizes the molecular mechanisms by which circadian rhythm regulates the digestive system, liver and bile acid production, and kidney function. We review research progress on intervention in the circadian rhythm by traditional Chinese medicine and provide a reasonable and valuable basis for follow-up studies on the role of traditional Chinese medicine in research on the molecular mechanisms of regulation of circadian rhythm.
Key words:    biological clock    metabolism    molecular mechanism    traditional Chinese medicine   
收稿日期: 2020-06-05
DOI: 10.16438/j.0513-4870.2020-0690
基金项目: 国家自然科学基金资助项目(81774173);2019年山东省高等学校“青创科技计划”立项(2019KJM005);2018年山东省自然科学基金重大基础研究项目(ZR2018ZC1157).
通讯作者: 蒋海强,Tel:86-531-89628192,E-mail:jhq12723@163.com
Email: jhq12723@163.com
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参考文献:
[1] Hastings MH, Reddy AB, Maywood ES. A clockwork web:circadian timing in brain and periphery, in health and disease[J]. Nat Rev Neurosci, 2003, 4:649-661.
[2] Panda S. Multiple photopigments entrain the mammalian circadian oscillator[J]. Neuron, 2007, 53:619-621.
[3] Albrecht U. Timing to perfection:the biology of central and peripheral circadian clocks[J]. Neuron, 2012, 74:246-260.
[4] Mohawk JA, Green CB, Takahashi JS. Central and peripheral circadian clocks in mammals[J]. Annu Rev Neurosci, 2012, 35:445-462.
[5] Cermakian N, Sassone-Corsi P. Multilevel regulation of the circadian clock[J]. Nat Rev Mol Cell Biol, 2000, 1:59-67.
[6] Preitner N, Damiola F, Lopez-Molina L, et al. The orphan nuclear receptor Rev-erbα controls circadian transcription within the positive limb of the mammalian circadian oscillator[J]. Cell, 2002, 110:251-260.
[7] Yamajuku D, Shibata Y, Kitazawa M, et al. Cellular Dbp and E4BP4 proteins are critical for determining the period length of the circadian oscillator[J]. FEBS Lett, 2011, 585:2217-2222.
[8] Eckel-Mahan KL, Patel VR, Mohney RP, et al. Coordination of the transcriptome and metabolome by the circadian clock[J]. Proc Natl Acad U S A, 2012, 109:5541-5546.
[9] Gad A, Ueli S. Crosstalk between components of circadian and metabolic cycles in mammals[J]. Cell Metab, 2011, 13:125-137.
[10] Gachon F, Olela FF, Schaad O, et al. The circadian PAR-domain basic leucine zipper transcription factors Dbp, Tef, and HLF modulate basal and inducible xenobiotic detoxification[J]. Cell Metab, 2006, 4:25-36.
[11] Lumeng JC, Somashekar D, Appugliese D, et al. Shorter sleep duration is associated with increased risk for being overweight at ages 9 to 12 years[J]. Pediatrics, 2007, 120:1020-1029.
[12] Cappuccio FP, Taggart FM, Ngianga-Bakwin K, et al. Meta-analysis of short sleep duration and obesity in children and adults[J]. Sleep, 2008, 5:619-626.
[13] Kornmann B, Schaad O, Bujard H, et al. System-driven and oscillator-dependent circadian transcription in mice with a conditionally active liver clock[J]. PLoS Biol, 2007, 5:e34.
[14] Fleur SEL, Kalsbeek A, Wortel J. A daily rhythm in glucose tolerance a role for the suprachiasmatic nucleus[J]. Diabetes, 2001, 50:1237-1243.
[15] Kalsbeek A, La FS, Fliers E. Circadian control of glucose metabolism[J]. Mol Metab, 2014, 3:372-383.
[16] Rudic RD, McNamara P, Curtis AM, et al. Bmal1 and CLOCK, two essential components of the circadian clock, are involved in glucose homeostasis[J]. PLoS Biol, 2004, 2:e377.
[17] Zhang EE, Liu Y, Dentin R, et al. Cryptochrome mediates circadian regulation of cAMP signaling and hepatic gluconeogenesis[J]. Nat Med, 2010, 16:1152-1156.
[18] Filiano AN, Telisha MS, Russell J, et al. Chronic ethanol consumption disrupts the core molecular clock and diurnal rhythms of metabolic genes in the liver without affecting the suprachiasmatic nucleus[J]. PLoS One, 2013, 8:e71684.
[19] Clara BP, Alison HA, Kathryn MR, et al. Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice[J]. Science, 2013, 342:1243417.
[20] Fontaine C, Dubois G, Duguay Y, et al. The orphan nuclear receptor Rev-erbα is a peroxisome proliferator-activated receptor (PPAR) γ target gene and promotes PPARγ-induced adipocyte differentiation[J]. J Biol Chem, 2003, 278:37672-37680.
[21] Cheng HL, Mostoslavsky R, Saito S, et al. Developmental defects and p53 hyperacetylation in Sir2 homolog (SIRT1)-deficient mice[J]. Proc Natl Acad Sci U S A, 2003, 100:10794-10799.
[22] Hardie DG. AMP-activated/SNF1 protein kinases:conserved guardians of cellular energy[J]. Nat Rev Mol Cell Biol, 2007, 8:774-785.
[23] Calvo JA, Daniels TG, Wang X, et al. Muscle-specific expression of PPARγ coactivator-1α improves exercise performance and increases peak oxygen uptake[J]. J Appl Physiol, 2008, 104:1304-1312.
[24] La FSE, Kalsbeek A, Wortel J, et al. A daily rhythm in glucose tolerance:a role for the suprachiasmatic nucleus[J]. Diabetes, 2001, 50:1237-1243.
[25] Maouyo D, Sarfati P, Guan D, et al. Circadian rhythm of exocrine pancreatic secretion in rats:major and minor cycles[J]. Am J Physiol, 1993, 264:G792-G800.
[26] Saito H, Terada T, Shimakura J, et al. Regulatory mechanism governing the diurnal rhythm of intestinal H+/peptide cotransporter 1(PEPT1)[J]. Am J Physiol Gastrointest Liver Physiol, 2008, 295:G395-G402.
[27] Pan XY, Terada T, Irie M, et al. Diurnal rhythm of H+-peptide cotransporter in rat small intestine[J]. Am J Physiol:Gastroenterol Liver Physiol, 2002, 283:G57-G64.
[28] Sot KM, Polidarov L, Muslkov J, et al. Circadian regulation of electrolyte absorption in the rat colon[J]. Am J Physiol Gastrointest Liver Physiol, 2011, 301:G1066-G1074.
[29] Clench J, Reinberg A, Dziewanowska Z, et al. Circadian changes in the bioavailability and effects of indomethacin in healthy subjects[J]. Eur J Clin Pharmacol, 1981, 20:359-369.
[30] Ando H, Yanagihara H, Sugimoto K, et al. Daily rhythms of P-glycoprotein expression in mice[J]. Chronobiol Int, 2005, 22:655-665.
[31] Murakami Y, Higashi Y, Matsunaga N, et al. Circadian clock-controlled intestinal expression of the multidrug-resistance gene mdr1a in mice[J]. Gastroenterol, 2008, 135:1636-1644.
[32] Radzialowski,FM,Bousquet WF. Daily rhythmic variation in hepatic drug metabolism in the rat and mouse[J]. J Pharmacol Exp Ther, 1968, 163:229-238.
[33] Lavery DJ, Lopez-Molina L, Margueron R, et al. Circadian expression of the steroid 15α-hydroxylase (Cyp2a4) and coumarin 7-hydroxylase (Cyp2a5) genes in mouse liver is regulated by the PAR leucine zipper transcription factor Dbp[J]. Mol Cell Biol, 1999, 19:6488-6499.
[34] Zhao M, Zhang T, Yu F, et al. E4bp4 regulates carboxylesterase 2 enzymes through repression of the nuclear receptor Rev-erbα in mice[J]. Biochem Pharmacol, 2018, 152:293-301.
[35] Zhao M, Zhao H, Deng J, et al. Role of the CLOCK protein in liver detoxification[J]. Br J Pharmacol, 2019, 176:4639-4652.
[36] Zhao M, Zhao H, Lin LM, et al. Nuclear receptor co-repressor RIP140 regulates diurnal expression of cytochrome P4502b10 in mouse liver[J]. Xenobiotica, 2020. DOI:10.1080/00498254. 2020.1751342.
[37] Knoedler JR, Jose VM, Subramani A, et al. The paralogous Krüppel-like factors 9 and 13 regulate the mammalian cellular circadian clock output gene Dbp[J]. J Biol Rhythms, 2020, 35:257-274.
[38] Zhang T, Guo L, Yu F, et al. The nuclear receptor Rev-erbα participates in circadian regulation of Ugt2b enzymes in mice[J]. Biochem Pharmacol, 2019, 161:89-97.
[39] Pons M, Forpomès O, Espagnet S, et al. Relationship between circadian changes in renal hemodynamics and circadian changes in urinary glycosaminoglycan excretion in normal rats[J]. Chronobiol Int, 1996, 13:349-358.
[40] Rackley RJ, Meyer MC, Straughn AB. Circadian rhythms in theophylline disposition:simulations and observations in the dog[J]. J Pharm Sci, 1991, 80:824-829.
[41] White CA, Pardue R, Huang C, et al. Chronobiological evaluation of the active biliary and renal secretion of ampicillin[J]. Chronobiol Int, 1995, 12:410-418.
[42] Rohman MS, Emoto N, Nonaka H, et al. Circadian clock genes directly regulate expression of the Na+/H+ exchanger NHE3 in the kidney[J]. Kidney Int, 2005, 67:1410-1419.
[43] Boughattas NA, Levi F, Fournier C, et al. Stable circadian mechanisms of toxicity of two platinum analogs (cisplatin and carboplatin) despite repeated dosages in mice[J]. J Pharmacol Exp Ther, 1990, 255:672-679.
[44] Lévi F, Benavides M, Chevelle C, et al. Chemotherapy of advanced ovarian cancer with 4'-O-tetrahydropyranyl doxorubicin and cisplatin:a randomized phase Ⅱ trial with an evaluation of circadian timing and dose-intensity[J]. J Clin Oncol, 1990, 8:705-714.
[45] Oda M, Koyanagi S, Tsurudome Y, et al. Renal circadian clock regulates the dosing-time dependency of cisplatin-induced nephrotoxicity in mice[J]. Mol Pharmacol, 2014, 85:715-722.
[46] Li T, Chiang JYL. Bile acid signaling in metabolic disease and drug therapy[J]. Pharmacolo Rev, 2014, 66:948-983.
[47] Stanimirov B, Stankov K, Mikov M. Bile acid signaling through farnesoid X and TGR5 receptors in hepatobiliary and intestinal diseases[J]. Hepatobiliary Pancreatic Dis Int, 2015, 14:18-33.
[48] Kovár J, Lenícek M, Zimolová M, et al. Regulation of diurnal variation of cholesterol 7α-hydroxylase (Cyp7a1) activity in healthy subjects[J]. Physiol Res, 2009, 59:233-238.
[49] Falvey E, Fleury-Olela F, Schibler U. The rat hepatic leukemia factor (HLF) gene encodes two transcriptional activators with distinct circadian rhythms, tissue distributions and target preferences[J]. EMBO J, 1995, 14:4307-4317.
[50] Amani AK, Sara S, Veronika V, et al. Asynchronous rhythms of circulating conjugated and unconjugated bile acids in the modulation of human metabolism[J]. J Int Med, 2018, 284:546-559.
[51] Jennifer YK, Guo GL, Klaassen CD, et al. Diurnal variations of mouse plasma and hepatic bile acid concentrations as well as expression of biosynthetic enzymes and transporters[J]. PLoS One, 2011, 6:e16683.
[52] Han S, Zhang R, Jain R, et al. Circadian control of bile acid synthesis by a KLF15-Fgf15 axis[J]. Nat Commun, 2015, 6:7231.
[53] Jeyaraj D, Scheer FJL, Ripperger JA, et al. Klf15 orchestrates circadian nitrogen homeostasis[J]. Cell Metab, 2012, 15:311-323.
[54] Langley RJ, Tsalik EL, Velkinburgh JCV, et al. An integrated clinico-metabolomic model improves prediction of death in sepsis[J]. Sci Transl Med, 2013, 5:700-708.
[55] Kinross JM, Holmes E. Metabolic phenotyping for monitoring surgical patients[J]. Lancet, 2011, 377:1817-1819.
[56] Nicholson JK, Elaine H, Kinross JM, et al. Metabolic phenotyping in clinical and surgical environments[J]. Nature, 2012, 491:384-392.
[57] Chen M, Zhou C, Xu HM, et al. Chronopharmacological targeting of Rev-erbα by puerarin alleviates hyperhomocysteinemia in mice[J]. Biomed Pharmacother, 2020, 125:109936.
[58] Yang ZM, Lin YK, Gao L, et al. Circadian clock regulates metabolism and toxicity of Fuzi (lateral root of Aconitum carmichaeli Debx) in mice[J]. Phytomedicine, 2020, 67:153161.
[59] Bian HS. Study on the Effect of Circadian Rhythm on Sleep Pattern and Energy Metabolism in Rats and the Intervention Effect of Melatonin (昼夜节律对大鼠的睡眠模式和能量代谢的影响及褪黑素的干预作用研究)[D]. Harbin:Heilongjiang University of Traditional Chinese Medicine, 2015.
[60] Wen M. Effects of Sea Cucumber Saponins on Mouse Biological Clock and Lipid Metabolism Gene Rhythm (海参皂苷对小鼠生物钟及脂质代谢基因节律的影响)[D]. Qingdao:Ocean University of China, 2014.
[61] Sun LJ. Resveratrol Regulates Biological Rhythm and Intervenes Lipid Metabolism in Mice with High Fat Diet (白藜芦醇调节生物节律干预高脂膳食小鼠脂代谢的研究)[D]. Zhenjiang:Jiangnan University, 2015.
[62] Zhu CS. Study on the Intervention Effect and Mechanism of Fufang Zhenzhu Tiaozhi Decoction on Mouse Model of Glucose and Lipid Metabolism Disturbance Caused by Circadian Rhythm (复方贞术调脂方对昼夜节律失调所致糖脂代谢紊乱小鼠模型的干预作用及机制研究)[D]. Guangzhou:Guangdong Pharmaceutical University, 2016.
[63] Zhang XY, Chao J, Wang HT, et al. Effect of Shenqi Fufang on circadian rhythm of type 2 diabetic GK rats[J]. J Pract Med (实用医学杂志), 2020, 36:874-879.
[64] Han YN, Lu B, Long M, et al. Effects of Huoxue Qianyang Qutan recipe on ambulatory blood pressure, blood pressure variability and blood pressure circadian rhythm in obese hypertensive patients[J]. Chin J Integr Med Cardio-Cerebrovasc Dis (中西医结合心脑血管病杂志), 2020, 18:41-44.
[65] Meng MD, Feng Y, Wang P, et al. Regulatory effect of polar extract of Poria cocos on neurotransmitter and circadian rhythm disorder in CUMS rats[J]. Chin Tradit Herb Drugs (中草药), 2020, 51:118-126.
[66] Zhang MY. Based on the Regulation of Circadian Clock Genes on Inflammatory Factors, the Intervention Effect of Huitang on Alzheimer's Disease (基于生物钟基因对炎症因子的调控研究生慧汤对阿尔茨海默病的干预作用)[D]. Wuhan:Hubei University of Traditional Chinese Medicine, 2019.
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