基于尿液代谢组学的玉米须治疗Ⅱ型糖尿病大鼠的作用机制研究
|
摘要
目的观察玉米须水煎液对Ⅱ型糖尿病大鼠尿液内源性代谢物的干扰规律,从代谢组学方面探讨玉米须的降糖作用机制。方法将Wistar大鼠用高糖高脂饲料喂养4周后,并结合腹腔注射小剂量链脲佐菌素复制Ⅱ型糖尿病模型。将成模后的大鼠分成模型对照组和玉米须给药组,玉米须给药组灌胃玉米须水煎液(10.8 g·kg~(-1))4周,给药期间观察大鼠状态,并每两周监测1次血糖值。给药治疗后,收集禁食12 h尿样,采用UPLC/Q-TOF-MS技术,结合主成分分析和正交偏最小二乘法-判别分析方法,分析其代谢谱的变化。结果玉米须水煎液可以明显降低糖尿病大鼠的血糖值并改善相关症状。在正负离子模式下,共筛选出12个差异性标志物,这些差异标志物包括鹅去氧胆酸、甘氨胆酸、精氨琥珀酸等。结论玉米须水煎液降糖作用机制可能与三羧酸循环、胆汁酸生物合成、色氨基酸代谢等代谢有关,并提示可能对肝肾功能起到一定的保护作用。
Aim To observe the interference of corn water decoction on endogenous metabolites in urine of rats with type 2 diabetes mellitus(T2 DM), and to investigate the hypoglycemic mechanism of corn silk in metabonomics.Methods Wistar rats were fed with high-sugar and high-fat diet for four weeks, and a small dose of streptozotocin was intraperitoneally injected to replicate the T2 DM model. The modeled rats were divided into model control group and corn silk group. The corn silk group was given water to the corn water decoction(10.8 g·kg~(-1)) for four weeks. The state of the rats was observed during the administration, and blood glucose levels were monitored every two weeks. After treatment, the fasted 12 h urine samples were collected and the changes analyzed by UPLC/QTOF-MS combined with principal component analysis and orthogonal partial least squares-discriminant analysis methods. Results Maize water decoction could significantly reduce blood glucose levels and improve symptoms in diabetic rats. In the positive and negative ion modes, a total of 12 differential markers were screened. These differential markers include chenodeoxycholic acid, glycocholic acid, argininosuccinic acid,etc. Conclusions The hypoglycemic mechanism of corn decoction may be related to the metabolism of tricarboxylic acid,biosynthesis of bile acids,metabolism of color amino acid,etc. It also suggests that it may play a protective role in liver and kidney function.
Aim To observe the interference of corn water decoction on endogenous metabolites in urine of rats with type 2 diabetes mellitus(T2 DM), and to investigate the hypoglycemic mechanism of corn silk in metabonomics.Methods Wistar rats were fed with high-sugar and high-fat diet for four weeks, and a small dose of streptozotocin was intraperitoneally injected to replicate the T2 DM model. The modeled rats were divided into model control group and corn silk group. The corn silk group was given water to the corn water decoction(10.8 g·kg~(-1)) for four weeks. The state of the rats was observed during the administration, and blood glucose levels were monitored every two weeks. After treatment, the fasted 12 h urine samples were collected and the changes analyzed by UPLC/QTOF-MS combined with principal component analysis and orthogonal partial least squares-discriminant analysis methods. Results Maize water decoction could significantly reduce blood glucose levels and improve symptoms in diabetic rats. In the positive and negative ion modes, a total of 12 differential markers were screened. These differential markers include chenodeoxycholic acid, glycocholic acid, argininosuccinic acid,etc. Conclusions The hypoglycemic mechanism of corn decoction may be related to the metabolism of tricarboxylic acid,biosynthesis of bile acids,metabolism of color amino acid,etc. It also suggests that it may play a protective role in liver and kidney function.
引文
[1] 国家药典委员会. 中国药典1977年版一部[M]. 北京:中国医药科技出版社, 1997: 126. National Pharmacopoeia Commission. Chinese Pharmacopoeia 1977 Part I[M]. Beijing: China Medical Science Press, 1997:126.
[2] 张培丽, 庄岩, 霍金海, 等. 玉米须有效化学成分及药理作用的研究概况[J]. 黑龙江中医药, 2017, 46(1): 74-5. Zhang P L, Zhuang Y, Huo J H, et al. Study on the research of effective chemical constituents and pharmacological effects of corn sorghum[J]. Heilongjiang J Tradit Chin Med, 2017, 46(1): 74-5.
[3] Dai B, Wu Q, Zeng C, et al. The effect of Liuwei Dihuang decoction on PI3K/Akt signaling pathway in liver of type 2 diabetes mellitus(T2DM) rats with insulin resistance[J]. J Ethnopharmacol, 2016, 192: 382-9.
[4] 秦昆明, 王彬, 陈林伟, 等. 代谢组学在中药现代研究的应用及展望[J]. 中国中药杂志, 2014, 39(16): 3010-7. Qin K M, Wang B, Chen L W, et al. Perspective and application of metabonomics in modern study of traditional Chinese medicine[J]. China J Chin Mater Med,2014, 39(16): 3010-7.
[5] 张廷模, 彭成. 中华临床中药学[M]. 北京:人民卫生出版社, 2015:844-5. Zhang T M, Peng C. Chinese Traditional Chinese Medicine[M]. Beijing: People’s Medical Publishing House, 2015: 844-5.
[6] 蔡爽. 糖尿病大鼠模型和抗糖尿病药物作用机制的代谢组学研究[D]. 沈阳: 沈阳药科大学, 2009. Cai S. Metabonomics study of diabetic rat model and anti-diabetic drug action mechanism[D].Shenyang: Shenyang Pharmaceutical University, 2009.
[7] Wang T J, Larson M G, Vasan R S, et al. Metabolite profiles and the risk of developing diabetes[J]. Nat Med, 2011, 17(4): 448-53.
[8] Zhang X R, Fu X J, Zhu D S, et al. Salidroside-regulated lipid metabolism with down-regulation of miR-370 in type 2 diabetic mice[J]. Eur J Pharmacol, 2016, 779: 46-52.
[9] 谷金宁, 牛俊, 皮子凤, 等. 尿液代谢组学方法研究人参总皂苷治疗糖尿病心肌病大鼠作用机制[J]. 分析化学, 2013, 41(3): 371-6. Gu J N, Niu J, Pi Z F, et al. Study on the mechanism of urinary metabolomics in the treatment of diabetic cardiomyopathy in rats with total saponins[J]. Chin J Anal Chem, 2013, 41(3): 371-6.
[10] 常晋霞, 刘文虎, 张建武. 刺五加提取物治疗糖尿病小鼠血清UPLC-MS/MS代谢组学研究[J]. 国际药学研究杂志, 2017, 44(7): 730-7. Chang J X, Liu W H, Zhang J W. Study on serum UPLC-MS/MS metabolomics of diabetic mice treated with Acanthopanax Senticosus extract[J].Int J Pharm Res, 2017, 44(7): 730-7.
[11] 吴丽梦, 叶剑芳, 谢文慧, 等. 白三烯B4在类风湿关节炎发病中的作用[J]. 中国免疫学杂志, 2014, 30(5): 689-93. Wu L M, Ye J F, Xie W H, et al. The role of leukotriene B4 in the pathogenesis of rheumatoid arthritis[J]. Chin J Immunol, 2014, 30(5): 689-93.
[12] Rodríguez-Ramiro I, Ramos S, Bravo L, et al. Procyanidin B2 induces Nrf2 translocation and glutathione S-transferase P1 expression via ERKs and p38-MAPK pathways and protect human colonic cells against oxidative stress[J]. Eur J Nutr, 2012, 51(7): 881-92.
[13] 李海燕, 张欢欢, 杨彦平, 等. 谷胱甘肽S-转移酶M1基因多态性与糖尿病相关性研究[J].贵州医药, 2016, 40(6): 567-8. Li H Y, Zhang H H, Yang Y P, et al. Relationship between glutathione S-transferase M1 gene polymorphism and diabetes mellitus[J]. Guizhou Med J, 2016, 40(6): 567-8.
[14] 徐小惠, 范氏泰和, 韦晓洁, 等. 杨桃根总提取物对糖尿病小鼠肾功能及其抗氧化应激作用的研究[J]. 中国药理学通报, 2017, 33(1): 95-100. Xu X H, Fan S T H, Wei X J, et al. Study on the effect of total extract of carambola root on renal function and antioxidative stress in diabetic mice[J]. Chin Pharmacol Bull, 2017, 33(1): 95-100.
[15] 李吉萍, 袁野, 张文友. 西洋参茎叶皂苷对糖尿病大鼠氧化损伤和血管内皮功能的影响[J]. 中国药理学通报, 2017, 33(12): 1698-702. Li J P, Yuan Y, Zhang W Y. Effects of Panax quinquefolium saponin on oxidative damage and endothelial function in diabetic rats[J]. Chin Pharmacol Bull, 2017, 33(12): 1698-702.
[2] 张培丽, 庄岩, 霍金海, 等. 玉米须有效化学成分及药理作用的研究概况[J]. 黑龙江中医药, 2017, 46(1): 74-5. Zhang P L, Zhuang Y, Huo J H, et al. Study on the research of effective chemical constituents and pharmacological effects of corn sorghum[J]. Heilongjiang J Tradit Chin Med, 2017, 46(1): 74-5.
[3] Dai B, Wu Q, Zeng C, et al. The effect of Liuwei Dihuang decoction on PI3K/Akt signaling pathway in liver of type 2 diabetes mellitus(T2DM) rats with insulin resistance[J]. J Ethnopharmacol, 2016, 192: 382-9.
[4] 秦昆明, 王彬, 陈林伟, 等. 代谢组学在中药现代研究的应用及展望[J]. 中国中药杂志, 2014, 39(16): 3010-7. Qin K M, Wang B, Chen L W, et al. Perspective and application of metabonomics in modern study of traditional Chinese medicine[J]. China J Chin Mater Med,2014, 39(16): 3010-7.
[5] 张廷模, 彭成. 中华临床中药学[M]. 北京:人民卫生出版社, 2015:844-5. Zhang T M, Peng C. Chinese Traditional Chinese Medicine[M]. Beijing: People’s Medical Publishing House, 2015: 844-5.
[6] 蔡爽. 糖尿病大鼠模型和抗糖尿病药物作用机制的代谢组学研究[D]. 沈阳: 沈阳药科大学, 2009. Cai S. Metabonomics study of diabetic rat model and anti-diabetic drug action mechanism[D].Shenyang: Shenyang Pharmaceutical University, 2009.
[7] Wang T J, Larson M G, Vasan R S, et al. Metabolite profiles and the risk of developing diabetes[J]. Nat Med, 2011, 17(4): 448-53.
[8] Zhang X R, Fu X J, Zhu D S, et al. Salidroside-regulated lipid metabolism with down-regulation of miR-370 in type 2 diabetic mice[J]. Eur J Pharmacol, 2016, 779: 46-52.
[9] 谷金宁, 牛俊, 皮子凤, 等. 尿液代谢组学方法研究人参总皂苷治疗糖尿病心肌病大鼠作用机制[J]. 分析化学, 2013, 41(3): 371-6. Gu J N, Niu J, Pi Z F, et al. Study on the mechanism of urinary metabolomics in the treatment of diabetic cardiomyopathy in rats with total saponins[J]. Chin J Anal Chem, 2013, 41(3): 371-6.
[10] 常晋霞, 刘文虎, 张建武. 刺五加提取物治疗糖尿病小鼠血清UPLC-MS/MS代谢组学研究[J]. 国际药学研究杂志, 2017, 44(7): 730-7. Chang J X, Liu W H, Zhang J W. Study on serum UPLC-MS/MS metabolomics of diabetic mice treated with Acanthopanax Senticosus extract[J].Int J Pharm Res, 2017, 44(7): 730-7.
[11] 吴丽梦, 叶剑芳, 谢文慧, 等. 白三烯B4在类风湿关节炎发病中的作用[J]. 中国免疫学杂志, 2014, 30(5): 689-93. Wu L M, Ye J F, Xie W H, et al. The role of leukotriene B4 in the pathogenesis of rheumatoid arthritis[J]. Chin J Immunol, 2014, 30(5): 689-93.
[12] Rodríguez-Ramiro I, Ramos S, Bravo L, et al. Procyanidin B2 induces Nrf2 translocation and glutathione S-transferase P1 expression via ERKs and p38-MAPK pathways and protect human colonic cells against oxidative stress[J]. Eur J Nutr, 2012, 51(7): 881-92.
[13] 李海燕, 张欢欢, 杨彦平, 等. 谷胱甘肽S-转移酶M1基因多态性与糖尿病相关性研究[J].贵州医药, 2016, 40(6): 567-8. Li H Y, Zhang H H, Yang Y P, et al. Relationship between glutathione S-transferase M1 gene polymorphism and diabetes mellitus[J]. Guizhou Med J, 2016, 40(6): 567-8.
[14] 徐小惠, 范氏泰和, 韦晓洁, 等. 杨桃根总提取物对糖尿病小鼠肾功能及其抗氧化应激作用的研究[J]. 中国药理学通报, 2017, 33(1): 95-100. Xu X H, Fan S T H, Wei X J, et al. Study on the effect of total extract of carambola root on renal function and antioxidative stress in diabetic mice[J]. Chin Pharmacol Bull, 2017, 33(1): 95-100.
[15] 李吉萍, 袁野, 张文友. 西洋参茎叶皂苷对糖尿病大鼠氧化损伤和血管内皮功能的影响[J]. 中国药理学通报, 2017, 33(12): 1698-702. Li J P, Yuan Y, Zhang W Y. Effects of Panax quinquefolium saponin on oxidative damage and endothelial function in diabetic rats[J]. Chin Pharmacol Bull, 2017, 33(12): 1698-702.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |