A preliminary study on metabonomics of amino acid and glucose in patients with gallbladder stones based on nuclear magnetic resonance_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

MA Wenjie ¹ , CHEN Weiwei ² , YANG Qin ¹ ,  LI Quansheng ¹ , LI Fuyu ¹

1. Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;
2. Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;

Corresponding author：

LI Quansheng, Email: 269371698@qq.com

Keywords：

gallbladder stones; nuclear magnetic resonance; metabonomics; serum; bile

DOI：

10.7507/1007-9424.201709077

Video：

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Objective The method of metabonomics based on nuclear magnetic resonance (NMR) imaging was used to explore the difference in metabolites of serum and bile, and to analyze the metabolic variation related to the pathogenesis of gallbladder stones between normal people/liver transplantation donors and patients with gallbladder stones. Methods Prospectively collected the serum samples (17 cases) and bile samples (19 cases) in 19 patients with gallbladder stones who underwent surgery in West China Hospital form March 2016 to December 2016, as well as the serum samples of 10 healthy persons and the bile samples of 15 liver transplantation donors at the same time period. The differences of metabolites in the blood and bile in these 3 groups were compared by using ¹H-NMR metabonomics technology and chemometric methods. Results The concentrations of valine, alanine, lysine, glutamine, glutamate, pyruvate, creatinine, choline, alpha-glucose, beta-glucose, tyrosine, histidine, and hypoxanthine in serum of patients with gallbladder stones decreased significantly, comparing with those of healthy people without gallbladder stones (P<0.05), while 1, 2-propanediol, acetoacetate, and lactate increased significantly in the serum of patients with gallbladder stones (P<0.05). The concentrations of taurine conjugated bile acids, glycine conjugated bile acids, choline, and phosphatidylcholine decreased significantly in the bile of patients with gallbladder stones when compared with those of liver transplantation donors (P<0.05), while cholesterol increased significantly in the bile of patients with gallbladder stones (P<0.05). Conclusions There are significant differences of the serum and bile metabolites between patients with gallbladder stones and healthy men without gallbladder stones/liver transplantation donors. ¹H-NMR metabonomics is helpful to investigate the pathogenesis of gallbladder stones.

Citation： MA Wenjie, CHEN Weiwei, YANG Qin, LI Quansheng, LI Fuyu. A preliminary study on metabonomics of amino acid and glucose in patients with gallbladder stones based on nuclear magnetic resonance. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2018, 25(4): 401-409. doi: 10.7507/1007-9424.201709077 Copy

1.	刘清, 金俊哲, 吕洪洋, 等. 胆囊结石的相关危险因素分析. 中国普外基础与临床杂志, 2016, 23(12): 1492-1495.
2.	吴大卫. 胆囊结石成因及其相关关系研究综述. 医学信息 (中旬刊), 2011, 24(8): 4124-4125.
3.	Gurusamy KS, Davidson BR. Gallstones. BMJ, 2014, 348: g2669.
4.	汪小辉, 邓侠兴, 祝哲诚, 等. 从胆石成因机制分析胆囊切除术治疗胆石病. 肝胆胰外科杂志, 2011, 23(1): 41-42.
5.	李彦东, 吴琪. 代谢组学技术在临床诊断中的研究进展. 天津医药, 2015, 43(8): 942-945.
6.	江春迎, 王映红. 基于核磁共振技术的定量代谢组学研究. 药学学报, 2014, 49(7): 949-955.
7.	Holmes E, Wijeyesekera A, Taylor-Robinson SD, et al. The promise of metabolic phenotyping in gastroenterology and hepatology. Nat Rev Gastroenterol Hepatol, 2015, 12(8): 458-471.
8.	Kimhofer T, Fye H, Taylor-Robinson S, et al. Proteomic and metabonomic biomarkers for hepatocellular carcinoma: a comprehensive review. Br J Cancer, 2015, 112(7): 1141-1156.
9.	Murakami Y, Kubo S, Tamori A, et al. Comprehensive analysis of transcriptome and metabolome analysis in intrahepatic cholangiocarcinoma and hepatocellular carcinoma. Sci Rep, 2015, 5: 16294.
10.	谭宜将, 刘衍民. 胆囊结石发病原因研究现状与进展. 中国实用外科杂志, 2009, 29(7): 602-603, 606.
11.	李瑞斌, 李艳茹, 万智恒, 等. 胆囊结石的形成原因及机制. 世界最新医学信息文摘 (电子版), 2015, 15(23): 39.
12.	周辉芳, 张晓玲, 史美瑗. 胆囊结石病因与致石疾病研究进展. 河北医科大学学报, 2010, 31(8): 1029-1032.
13.	Behar J, Mawe GM, Carey MC. Roles of cholesterol and bile salts in the pathogenesis of gallbladder hypomotility and inflammation: cholecystitis is not caused by cystic duct obstruction. Neurogastroenterol Motil, 2013, 25(4): 283-290.
14.	Wasinski F, Gregnani MF, Ornellas FH, et al. Lymphocyte glucose and glutamine metabolism as targets of the anti-inflammatory and immunomodulatory effects of exercise. Mediators Inflamm, 2014, 2014: 326803.
15.	Sharma RK, Mishra K, Farooqui A, et al. ¹H nuclear magnetic resonance (NMR)-based serum metabolomics of human gallbladder inflammation. Inflamm Res, 2017, 66(1): 97-105.
16.	唐乾利, 黄欣, 俞渊, 等. 兔胆石症的代谢组学特征及大黄灵仙胶囊的干预作用. 医药导报, 2013, 32(12): 1538-1542.
17.	Li FY, Cheng NS, Mao H, et al. Significance of controlling chronic proliferative cholangitis in the treatment of hepatolithiasis. World J Surg, 2009, 33(10): 2155-2160.
18.	Su Y, Wu S, Fan Y, et al. The preliminary experimental and clinical study of the relationship between the pigment gallstone and intestinal mucosal barrier. J Gastroenterol Hepatol, 2009, 24(8): 1451-1456.
19.	Tanaka S. Physiological function mediated by histamine synthesis. Yakugaku Zasshi, 2003, 123(7): 547-559.
20.	Watanabe M, Suliman ME, Qureshi AR, et al. Consequences of low plasma histidine in chronic kidney disease patients: associations with inflammation, oxidative stress, and mortality. Am J Clin Nutr, 2008, 87(6): 1860-1866.
21.	Lee YT, Hsu CC, Lin MH, et al. Histidine and carnosine delay diabetic deterioration in mice and protect human low density lipoprotein against oxidation and glycation. Eur J Pharmacol, 2005, 513(1-2): 145-150.
22.	Son DO, Satsu H, Shimizu M. Histidine inhibits oxidative stress- and TNF-alpha-induced interleukin-8 secretion in intestinal epithelial cells. FEBS Lett, 2005, 579(21): 4671-4677.
23.	Liu Y, Wang X, Hu CA. Therapeutic potential of amino acids in inflammatory bowel disease. Nutrients, 2017, 9(9): 18.
24.	Stifel FB, Herman RH. Is histidine an essential amino acid in man? Am J Clin Nutr, 1972, 25(2): 182-185.
25.	Khovidhunkit W, Kim MS, Memon RA, et al. Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host. J Lipid Res, 2004, 45(7): 1169-1196.
26.	Müller O, Schalla C, Scheibner J, et al. Expression of liver plasma membrane transporters in gallstone-susceptible and gallstone-resistant mice. Biochem J, 2002, 361(Pt 3): 673-679.
27.	俞渊, 唐乾利, 黄欣, 等. 大黄灵仙胶囊防治兔胆石病的代谢组学及超微病理研究. 中华中医药杂志, 2013, 28(11): 3359-3362.
28.	Tazuma S, Kanno K, Sugiyama A, et al. Nutritional factors (nutritional aspects) in biliary disorders: bile acid and lipid metabolism in gallstone diseases and pancreaticobiliary maljunction. J Gastroenterol Hepatol, 2013, 28 Suppl 4: 103-107.
29.	O’Connell K, Brasel K. Bile metabolism and lithogenesis. Surg Clin North Am, 2014, 94(2): 361-375.

1. 刘清, 金俊哲, 吕洪洋, 等. 胆囊结石的相关危险因素分析. 中国普外基础与临床杂志, 2016, 23(12): 1492-1495.
2. 吴大卫. 胆囊结石成因及其相关关系研究综述. 医学信息 (中旬刊), 2011, 24(8): 4124-4125.
3. Gurusamy KS, Davidson BR. Gallstones. BMJ, 2014, 348: g2669.
4. 汪小辉, 邓侠兴, 祝哲诚, 等. 从胆石成因机制分析胆囊切除术治疗胆石病. 肝胆胰外科杂志, 2011, 23(1): 41-42.
5. 李彦东, 吴琪. 代谢组学技术在临床诊断中的研究进展. 天津医药, 2015, 43(8): 942-945.
6. 江春迎, 王映红. 基于核磁共振技术的定量代谢组学研究. 药学学报, 2014, 49(7): 949-955.
7. Holmes E, Wijeyesekera A, Taylor-Robinson SD, et al. The promise of metabolic phenotyping in gastroenterology and hepatology. Nat Rev Gastroenterol Hepatol, 2015, 12(8): 458-471.
8. Kimhofer T, Fye H, Taylor-Robinson S, et al. Proteomic and metabonomic biomarkers for hepatocellular carcinoma: a comprehensive review. Br J Cancer, 2015, 112(7): 1141-1156.
9. Murakami Y, Kubo S, Tamori A, et al. Comprehensive analysis of transcriptome and metabolome analysis in intrahepatic cholangiocarcinoma and hepatocellular carcinoma. Sci Rep, 2015, 5: 16294.
10. 谭宜将, 刘衍民. 胆囊结石发病原因研究现状与进展. 中国实用外科杂志, 2009, 29(7): 602-603, 606.
11. 李瑞斌, 李艳茹, 万智恒, 等. 胆囊结石的形成原因及机制. 世界最新医学信息文摘 (电子版), 2015, 15(23): 39.
12. 周辉芳, 张晓玲, 史美瑗. 胆囊结石病因与致石疾病研究进展. 河北医科大学学报, 2010, 31(8): 1029-1032.
13. Behar J, Mawe GM, Carey MC. Roles of cholesterol and bile salts in the pathogenesis of gallbladder hypomotility and inflammation: cholecystitis is not caused by cystic duct obstruction. Neurogastroenterol Motil, 2013, 25(4): 283-290.
14. Wasinski F, Gregnani MF, Ornellas FH, et al. Lymphocyte glucose and glutamine metabolism as targets of the anti-inflammatory and immunomodulatory effects of exercise. Mediators Inflamm, 2014, 2014: 326803.
15. Sharma RK, Mishra K, Farooqui A, et al. ¹H nuclear magnetic resonance (NMR)-based serum metabolomics of human gallbladder inflammation. Inflamm Res, 2017, 66(1): 97-105.
16. 唐乾利, 黄欣, 俞渊, 等. 兔胆石症的代谢组学特征及大黄灵仙胶囊的干预作用. 医药导报, 2013, 32(12): 1538-1542.
17. Li FY, Cheng NS, Mao H, et al. Significance of controlling chronic proliferative cholangitis in the treatment of hepatolithiasis. World J Surg, 2009, 33(10): 2155-2160.
18. Su Y, Wu S, Fan Y, et al. The preliminary experimental and clinical study of the relationship between the pigment gallstone and intestinal mucosal barrier. J Gastroenterol Hepatol, 2009, 24(8): 1451-1456.
19. Tanaka S. Physiological function mediated by histamine synthesis. Yakugaku Zasshi, 2003, 123(7): 547-559.
20. Watanabe M, Suliman ME, Qureshi AR, et al. Consequences of low plasma histidine in chronic kidney disease patients: associations with inflammation, oxidative stress, and mortality. Am J Clin Nutr, 2008, 87(6): 1860-1866.
21. Lee YT, Hsu CC, Lin MH, et al. Histidine and carnosine delay diabetic deterioration in mice and protect human low density lipoprotein against oxidation and glycation. Eur J Pharmacol, 2005, 513(1-2): 145-150.
22. Son DO, Satsu H, Shimizu M. Histidine inhibits oxidative stress- and TNF-alpha-induced interleukin-8 secretion in intestinal epithelial cells. FEBS Lett, 2005, 579(21): 4671-4677.
23. Liu Y, Wang X, Hu CA. Therapeutic potential of amino acids in inflammatory bowel disease. Nutrients, 2017, 9(9): 18.
24. Stifel FB, Herman RH. Is histidine an essential amino acid in man? Am J Clin Nutr, 1972, 25(2): 182-185.
25. Khovidhunkit W, Kim MS, Memon RA, et al. Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host. J Lipid Res, 2004, 45(7): 1169-1196.
26. Müller O, Schalla C, Scheibner J, et al. Expression of liver plasma membrane transporters in gallstone-susceptible and gallstone-resistant mice. Biochem J, 2002, 361(Pt 3): 673-679.
27. 俞渊, 唐乾利, 黄欣, 等. 大黄灵仙胶囊防治兔胆石病的代谢组学及超微病理研究. 中华中医药杂志, 2013, 28(11): 3359-3362.
28. Tazuma S, Kanno K, Sugiyama A, et al. Nutritional factors (nutritional aspects) in biliary disorders: bile acid and lipid metabolism in gallstone diseases and pancreaticobiliary maljunction. J Gastroenterol Hepatol, 2013, 28 Suppl 4: 103-107.
29. O’Connell K, Brasel K. Bile metabolism and lithogenesis. Surg Clin North Am, 2014, 94(2): 361-375.

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A preliminary study on metabonomics of amino acid and glucose in patients with gallbladder stones based on nuclear magnetic resonance

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