中国药学(英文版) ›› 2022, Vol. 31 ›› Issue (6): 441-451.DOI: 10.5246/jcps.2022.06.038
黄素琼#, 万敬员#, 杜婷婷#, 龚涛, 张静, 蒋心惠*()
收稿日期:
2021-12-24
修回日期:
2022-01-15
接受日期:
2022-03-30
出版日期:
2022-06-30
发布日期:
2022-06-30
通讯作者:
蒋心惠
作者简介:
基金资助:
Suqiong Huang#, Jingyuan Wan#, Tingting Du#, Tao Gong, Jing Zhang, Xinhui Jiang*()
Received:
2021-12-24
Revised:
2022-01-15
Accepted:
2022-03-30
Online:
2022-06-30
Published:
2022-06-30
Contact:
Xinhui Jiang
About author:
摘要:
非酒精性脂肪性肝病(NAFLD)是一种与酒精中毒、自身免疫和病毒感染无关的肝实质脂肪变性, 也是一种代谢相关综合征, 与脂肪组织功能障碍和肥胖有密切关系。肝性脑病(HE)是慢性肝病的严重并发症, 是肝病终末期综合征之一, 已有研究发现支链氨基酸(BCAAs)可通过影响氨代谢和能量代谢与HE发病相关。而有学者认为NAFLD与其他形式的肝损伤一样, 可能与BCAAs代谢紊乱有关。虽已有多项研究揭示了血清中氨基酸、HE和慢性肝病之间的关系, 但对NAFLD动物模型脑组织中氨基酸含量的研究较少。在这项研究中, 我们建立了邻苯二甲醛(OPA)衍生化高效液相色谱法(HPLC-FLD), 可同时检测非酒精性脂肪肝C57BL/6模型小鼠脑组织中13种氨基酸的含量, 通过对比不同NAFLD疾病进展过程中小鼠脑组织中氨基酸含量的变化, 发现C57BL/6小鼠脑内氨基酸含量的变化与非酒精性脂肪肝的疾病进展有关, 这种变化或与HE的发病机制存在潜在联系。
Supporting:
黄素琼, 万敬员, 杜婷婷, 龚涛, 张静, 蒋心惠. C57BL/6小鼠脑组织中13种氨基酸含量与NAFLD疾病进展的关系[J]. 中国药学(英文版), 2022, 31(6): 441-451.
Suqiong Huang, Jingyuan Wan, Tingting Du, Tao Gong, Jing Zhang, Xinhui Jiang. The relationship between the contents of 13 amino acids in brain tissues and the progression of NAFLD via C57BL/6 model mice[J]. Journal of Chinese Pharmaceutical Sciences, 2022, 31(6): 441-451.
Figure 1. (A) The section of model mouse liver tissue after 9 weeks of HFD feeding. A few Balloon-like steatosis could be seen under a microscope. (B) The section of model mouse liver tissue after 15 weeks of HFD feeding. Marked Balloon-like steatosis and inflammatory cells could be seen under a microscope.
Figure 2. Changes of amino acids in brain tissues of model group mice from week 3 to week 18. (A) The contents of Asp, Glu, Gln, Gly, Tau, and GABA were compared; (B) The contents of Tyr, Trp, Met, Val, Phe, Ile, and Leu were compared. *P<0.05, vs. 3-week group.
Table 1. The contents of 13 amino acids in brain tissues of C57BL/6 mice at different feeding cycles and their P values as compared with those in the 3-week group (mean ± SD).
[1] |
Masuoka, H.C.; Chalasani, N. Nonalcoholic fatty liver disease: an emerging threat to obese and diabetic individuals. Ann. NY Acad. Sci. 2013, 1281, 106–122.
|
[2] |
Whalley, S.; Puvanachandra, P.; Desai, A.; Kennedy, H. Hepatology outpatient service provision in secondary care: a study of liver disease incidence and resource costs. Clin. Med. Lond. Engl. 2007, 7, 119–124.
|
[3] |
Byrne, C.D.; Targher, G. NAFLD: a multisystem disease. J. Hepatol. 2015, 62, S47–S64.
|
[4] |
Jornayvaz, F.R.; Shulman, G.I. Diacylglycerol activation of protein kinase cε and hepatic insulin resistance. Cell Metab. 2012, 15, 574–584.
|
[5] |
Friedman, S.L.; Neuschwander-Tetri, B.A.; Rinella, M.; Sanyal, A.J. Mechanisms of NAFLD development and therapeutic strategies. Nat. Med. 2018, 24, 908–922.
|
[6] |
Ekstedt, M.; Franzén, L.E.; Mathiesen, U.L.; Thorelius, L.; Holmqvist, M.; Bodemar, G.; Kechagias, S. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatol. Baltim. Md. 2006, 44, 865–873.
|
[7] |
Mittal, S.; El-Serag, H.B.; Sada, Y.H.; Kanwal, F.; Duan, Z.G.; Temple, S.; May, S.B.; Kramer, J.R.; Richardson, P.A.; Davila, J.A. Hepatocellular carcinoma in the absence of cirrhosis in United States veterans is associated with nonalcoholic fatty liver disease. Clin. Gastroenterol. Hepatol. 2016, 14, 124–131.e1.
|
[8] |
Dyson, J.; Jaques, B.; Chattopadyhay, D.; Lochan, R.; Graham, J.; Das, D.; Aslam, T.; Patanwala, I.; Gaggar, S.; Cole, M.; Sumpter, K.; Stewart, S.; Rose, J.; Hudson, M.; Manas, D.; Reeves, H.L. Hepatocellular cancer: the impact of obesity, type 2 diabetes and a multidisciplinary team. J. Hepatol. 2014, 60, 110–117.
|
[9] |
Singh, S.; Allen, A.M.; Wang, Z.; Prokop, L.J.; Murad, M.H.; Loomba, R. Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies. Clin. Gastroenterol. Hepatol. 2015, 13, 643–654.e9.
|
[10] |
Huang, P.L. A comprehensive definition for metabolic syndrome. Dis. Models Mech. 2009, 2, 231–237.
|
[11] |
Käräjämäki, A.J.; Bloigu, R.; Kauma, H.; Kesäniemi, Y.A.; Koivurova, O.P.; Perkiömäki, J.; Huikuri, H.; Ukkola, O. Non-alcoholic fatty liver disease with and without metabolic syndrome: different long-term outcomes. Metabolism. 2017, 66, 55–63.
|
[12] |
Tsuneto, A.; Hida, A.; Sera, N.; Imaizumi, M.; Akahoshi, M. Fatty liver incidence and predictive variables. Hypertens. Res. 2010, 33, 638–43.
|
[13] |
Blachier, M.; Leleu, H.; Peck-Radosavljevic, M.; Valla, D.C.; Roudot-Thoraval, F. The burden of liver disease in Europe: a review of available epidemiological data. J. Hepatol. 2013, 58, 593–608.
|
[14] |
Loomba, R.; Abraham, M.; Unalp, A.; Wilson, L.; Lavine, J.; Doo, E.; Bass, N.M.; Nonalcoholic Steatohepatitis Clinical Research Network. Association between diabetes, family history of diabetes, and risk of nonalcoholic steatohepatitis and fibrosis. Hepatol. Baltim. Md. 2012, 56, 943–951.
|
[15] |
Holecek, M. Three targets of branched-chain amino acid supplementation in the treatment of liver disease. Nutrition. 2010, 26, 482–490.
|
[16] |
Rossi Fanelli, F.; Cangiano, C.; Capocaccia, L.; Cascino, A.; Ceci, F.; Muscaritoli, M.; Giunchi, G. Use of branched chain amino acids for treating hepatic encephalopathy: clinical experiences. Gut. 1986, 27, 111–115.
|
[17] |
Skalská, H.; Mráz, J.; Holeček, M. Plasma amino acid levels after carbon tetrachloride induced acute liver damage. A dose-response and time-response study in rats. Amino. Acids. 1999, 16, 1–11.
|
[18] |
Heberer, M.; Talke, H.; Maier, K.P.; Gerok, W. Metabolism of phenylalanine in liver diseases. Biochem. Biophys. Rep. 1980, 58, 1189–1196.
|
[19] |
Cascino, A.; Cangiano, C.; Calcaterra, V.; Rossi-Fanelli, F.; Capocaccia, L. Plasma amino acids imbalance in patients with liver disease. Am. J. Dig. Dis. 1978, 23, 591–598.
|
[20] |
Holeček, M. Relation between glutamine, branched-chain amino acids, and protein metabolism. Nutrition. 2002, 18, 130–133.
|
[21] |
Bernardini, P.; Fischer, J.E. Amino acid imbalance and hepatic encephalopathy. Annu. Rev. Nutr. 1982, 2, 419–454.
|
[22] |
Paul, H.S.; Adibi, S.A. Activation of hepatic branched chain alpha-keto acid dehydrogenase by a skeletal muscle factor. J. Biol. Chem. 1982, 257, 12581–12588.
|
[23] |
Damuni, Z.; Merryfield, M.L.; Humphreys, J.S.; Reed, L.J. Purification and properties of branched-chain alpha-keto acid dehydrogenase phosphatase from bovine kidney. Proc. Natl. Acad. Sci. USA. 1984, 81, 4335–4338.
|
[24] |
Aguirre, A.; Yoshimura, N.; Westman, T.; Fischer, J.E. Plasma amino acids in dogs with two experimental forms of liver damage. J. Surg. Res. 1974, 16, 339–345.
|
[25] |
McCullough, A.J.; Czaja, A.J.; Jones, J.D.; Go, V.L. The nature and prognostic significance of serial amino acid determinations in severe chronic active liver disease. Gastroenterology. 1981, 81, 645–652.
|
[26] |
Lieber, C.S.; Leo, M.A.; Mak, K.M.; Xu, Y.Q.; Cao, Q.; Ren, C.L.; Ponomarenko, A.; DeCarli, L.M. Model of nonalcoholic steatohepatitis. Am. J. Clin. Nutr. 2004, 79, 502–509.
|
[27] |
Soeters, P.B.; Weir, G.; Ebeid, A.M.; Fischer, J.E. Insulin, glucagon, portal systemic shunting, and hepatic failure in the dog. J. Surg Res. 1977, 23, 183–188.
|
[28] |
Nakaya, Y.; Okita, K.; Suzuki, K.; Moriwaki, H.; Kato, A.; Miwa, Y.; Shiraishi, K.; Okuda, H.; Onji, M.; Kanazawa, H.; Tsubouchi, H.; Kato, S.; Kaito, M.; Watanabe, A.; Habu, D.; Ito, S.; Ishikawa, T.; Kawamura, N.; Arakawa, Y. BCAA-enriched snack improves nutritional state of cirrhosis. Nutrition. 2007, 23, 113–120.
|
[29] |
Muto, Y.; Sato, S.; Watanabe, A.; Moriwaki, H.; Suzuki, K.; Kato, A.; Kato, M.; Nakamura, T.; Higuchi, K.; Nishiguchi, S.; Kumada, H.;. Effects of oral branched-chain amino acid granules on event-free survival in patients with liver cirrhosis. Clin. Gastroenterol. Hepatol. 2005, 3, 705–713.
|
[30] |
Kuwahata, M.; Yoshimura, T.; Sawai, Y.; Amano, S.; Tomoe, Y.; Segawa, H.; Tatsumi, S.; Ito, M.; Ishizaki, S.; Ijichi, C.; Sonaka, I.; Oka, T.; Miyamoto, K.I. Localization of polypyrimidine-tract-binding protein is involved in the regulation of albumin synthesis by branched-chain amino acids in HepG2 cells. J. Nutr. Biochem. 2008, 19, 438–447.
|
[31] |
Kuwahata, M.; Kubota, H.; Kanouchi, H.; Ito, S.; Ogawa, A.; Kobayashi, Y.; Kido, Y. Supplementation with branched-chain amino acids attenuates hepatic apoptosis in rats with chronic liver disease. Nutr. Res. 2012, 32, 522–529.
|
[32] |
Ikehara, O.; Kawasaki, N.; Maezono, K.; Komatsu, M.; Konishi, A. Acute and chronic treatment of L-isoleucine ameliorates glucose metabolism in glucose-intolerant and diabetic mice. Biol. Pharm. Bull. 2008, 31, 469–472.
|
[33] |
Korenaga, K.; Korenaga, M.; Uchida, K.; Yamasaki, T.; Sakaida, I. Effects of a late evening snack combined with α-glucosidase inhibitor on liver cirrhosis. Hepatol. Res. 2008, 38, 1087–1097.
|
[34] |
Kawaguchi, T.; Nagao, Y.; Matsuoka, H.; Ide, T.; Sata, M. Branched-chain amino acid-enriched supplementation improves insulin resistance in patients with chronic liver disease. Int. J. Mol. Med. 2008, 22, 105–112.
|
[35] |
Ono, J.; Hutson, D.G.; Dombro, R.S.; Levi, J.U.; Livingstone, A.; Zeppa, R. Tryptophan and hepatic coma. Gastroenterology. 1978, 74, 196–200.
|
[36] |
Chang, Y.Y.; Chou, C.H.; Chiu, C.H.; Yang, K.T.; Lin, Y.L.; Weng, W.L.; Chen, Y.C. Preventive effects of taurine on development of hepatic steatosis induced by a high-fat/cholesterol dietary habit. J. Agric. Food Chem. 2011, 59, 450–457.
|
[37] |
Vijaimohan, K.; Jainu, M.; Sabitha, K.E.; Subramaniyam, S.; Anandhan, C.; Shyamala Devi, C.S. Beneficial effects of alpha linolenic acid rich flaxseed oil on growth performance and hepatic cholesterol metabolism in high fat diet fed rats. Life Sci. 2006, 79, 448–454.
|
[38] |
Miyata, M.; Funaki, A.; Fukuhara, C.; Sumiya, Y.; Sugiura, Y. Taurine attenuates hepatic steatosis in a genetic model of fatty liver disease. J. Toxicol. Sci. 2020, 45, 87–94.
|
[39] |
Tang, R.; Yang, Q.; Lin, S.; Feng, Y.; Yang, J.; Lv, Q.; Wu, G.; Hu, J. Preventive or curative administration of taurine regulates lipid metabolism in the liver of rats with alcoholic liver disease. Adv. Exp. Med. Biol. 2019, 1155, 119–131.
|
[40] |
Zhao, D.; Lv, Q.; Yang, J.; Wu, G.; Liu, M.; Yang, Q.; Han, J.; Feng, Y.; Lin, S.; Hu, J. Taurine improves lipid metabolism and skeletal muscle sensitivity to insulin in rats fed with high sugar and high fat diet. Adv. Exp. Med. Biol. 2019, 1155, 133–146.
|
[41] |
Li, K.; Wang, D.; Zhou, X.; Shao, J.; Li, Y.; Liu, X.; Zhang, C.; Zuo, E.; Shi, X.; Piao, F.; Li, S. Taurine protects against arsenic-induced apoptosis via PI3K/Akt pathway in primary cortical neurons. Adv. Exp. Med. Biol. 2019, 1155, 747–754.
|
[42] |
Mantena, S.K.; King, A.L.; Andringa, K.K.; Eccleston, H.B.; Bailey, S.M. Mitochondrial dysfunction and oxidative stress in the pathogenesis of alcohol- and obesity-induced fatty liver diseases. Free. Radic. Biol. Med. 2008, 44, 1259–1272.
|
[43] |
Li, S.; Liao, X.; Meng, F.; Wang, Y.; Sun, Z.; Guo, F.; Li, X.; Meng, M.; Li, Y.; Sun, C. Therapeutic role of ursolic acid on ameliorating hepatic steatosis and improving metabolic disorders in high-fat diet-induced non-alcoholic fatty liver disease rats. PLoS One. 2014, 9, e86724.
|
[44] |
Anholt, R.R.; De Souza, E.B.; Oster-Granite, M.L.; Snyder, S.H. Peripheral-type benzodiazepine receptors: autoradiographic localization in whole-body sections of neonatal rats. J. Pharmacol. Exp. Ther. 1985, 233, 517–526.
|
[45] |
Castelli, M.P.; Ingianni, A.; Stefanini, E.; Gessa, G.L. Distribution of GABAB receptor mRNAs in the rat brain and peripheral organs. Life Sci. 1999, 64, 1321–1328.
|
[46] |
Gardner, L.B.; Hori, T.; Chen, F.; Baine, A.M.; Hata, T.; Uemoto, S.; Nguyen, J.H. Effect of specific activation of γ-aminobutyric acid receptor in vivo on oxidative stress-induced damage after extended hepatectomy. Hepatol. Res. 2012, 42, 1131–1140.
|
[1] | 李双, 董明纲, 郭春燕, 李双双, 尤斯涵, 万叶, 刘心星. 桃红四物汤颗粒通过改善线粒体功能障碍和氨基酸代谢紊乱缓解鱼藤酮诱导的SH-SY5Y细胞毒性作用[J]. 中国药学(英文版), 2023, 32(5): 360-378. |
[2] | 陈小青, 彭波, 姜红梅, 张昌旭, 李海燕, 李子银. 丹酚酸B通过介导SIRT3/FOXO1信号通路减轻非酒精性脂肪肝的氧化应激反应[J]. 中国药学(英文版), 2022, 31(9): 698-710. |
[3] | 许士琪, 朱礼岩, 郝超, 刘文倩, 陈成龙, 陈泳怡, 刘爱芹. 一种新型含氨基酸基团替加氟前药的合成及其抗肿瘤活性评价[J]. 中国药学(英文版), 2021, 30(9): 743-753. |
[4] | 北京大学药学院 天然药物及仿生药物国家重点实验室. 刘涛研究员团队在《Nature Chemical Biology》上发表非天然氨基酸调控的胰岛素分泌细胞治疗系统[J]. 中国药学(英文版), 2021, 30(11): 937-938. |
[5] | 石亚娟, 管清华, 吴艳芬, 王超. 含砷氨基酸的合成及其在多肽化学中的应用[J]. 中国药学(英文版), 2017, 26(5): 372-378. |
[6] | 王萌萌, 杜望春, 沈杰*, 董毅, 魏文石, 宋钟娟. 高效液相色谱荧光检测法测定小鼠脑组织中氨基酸类神经递质[J]. , 2013, 22(3): 239-243. |
[7] | 吕丽, 王江, 丁晓, 林岱宗, 赵临襄, 蒋华良, 柳红*. 镍螯合物(II) Suzuki 偶联反应诱导的α-取代β-氨基酸的合成[J]. , 2012, 21(6): 561-568. |
[8] | 李刚, 刘玉鹏, 雷蒙, 王欣*, 程铁明, 李润涛*. 以氨基酸甲酯和异硫氰酸酯为原料碱性Al2O3为载体合成硫代乙内酰脲的有效方法[J]. , 2012, 21(2): 136-141. |
[9] | 杨颖, 王超*. 多巯基功能性保护氨基酸的合成[J]. , 2011, 20(2): 195-198. |
[10] | 金鑫#, 孙婷婷#, 王琪, 徐欢, 魏铁军, 贺秋晨, 张礼和, 周德敏*. 可诱导RNA干扰系统及药物靶标确证 [J]. , 2009, 18(4): 293-301. |
[11] | 苗艳丽, 方富永, 宋文东*. 中药菲牛蛭化学成分的分析 [J]. , 2007, 16(3): 223-226. |
[12] | 刘晓岩, 李凤云, 池志宏, 王银叶*. 口服1,6-二磷酸果糖对动物肝损伤模型的保护作用[J]. , 2006, 15(3): 188-193. |
[13] | 车建途, 张均田, 陈飞松, 屈志炜. 粉防已碱对体外培养大鼠脑皮层神经元损伤的保护作用[J]. , 1997, 6(3): 143-148. |
[14] | 刘国湘, 胡文祥*, 胡德荣, 张新位, 恽榴红. 锗丙酰氨基酸酯倍半氧化物的合成[J]. , 1996, 5(3): 160-164. |
[15] | 李林峰, 张孙曦, 李世荫. 利福平及其蛋白偶联物致敏兔和利福平特异IgG检测[J]. , 1994, 3(2): 141-146. |
阅读次数 | ||||||
全文 |
|
|||||
摘要 |
|
|||||