目的 分析T3溶液诱导甲亢阴虚型模型大鼠后血清中内源性代谢物的变化，初步探讨玉竹多糖预防甲亢阴虚的作用机制。方法 将SD 大鼠随机分为正常组，模型组，玉竹多糖组(400 mg·kg-1);利用注射T3溶液于大鼠腹腔(500 μg·kg-1)连续1周建立甲亢阴虚模型，测定血浆中cAMP、cGMP、血清中T3、T4等指标。采用GC-MS技术分析大鼠血清代谢物图谱，运用软件Simca-P12.0进行多元统计分析。结果 玉竹多糖可以显著降低模型动物的T3、T4、cAMP、cAMP/cGMP含量，升高cGMP含量，对甲亢阴虚型大鼠具有一定的改善作用。PCA得分图显示正常组、模型组和玉竹组的代谢轮廓有明显差别，通过偏最小二乘-判别分析(PLS-DA)对样品进行进一步分型，根据模型的变量重要性因子(VIP 值)结果筛选差异代谢物，鉴定出9种内源性代谢物为生物标记物。结论 研究表明，玉竹多糖干预的甲亢阴虚型大鼠整体代谢轮廓趋向正常水平，通过调节糖代谢、能量代谢、氨基酸代谢及脂类代谢等对甲亢阴虚发挥预防作用，其所揭示的代谢途径变化将为阴虚诊断及治疗提供一定的依据。
Abstract
OBJECTIVE To evaluate the effect of Polygonatum odoratum polysaccharide(POP) on hyperthyroidism Yin-deficiency rats based on GC-MS metabolomics and explore its mechanism. METHODS SD rats were randomly divided into control, model and POP groups. The hyperthyroidism Yin-deficiency rats were treated by intraperitoneal injection of T3 for a week. The content of T3、T4 in serum and cAMP、cGMP in plasma was determined. A GC-MS based metabolic profiling method was employed to analyze the distinctive metabolic patterns of serum in control, model and POP. Multivariate statistical analysis was applied for multivariate analysis to find potential biomarkers of Yin-deficiency by SIMCA-P 12.0 software. RESULTS Compared with the model group, polygonatum polysaccharide can significantly reduce the content of T3, T4, cAMP, the ratio of cAMP/cGMP and increase the content of cGMP, indicating it has certain Yin-nourishing action. The PCA score plot showed metabolic profiling of control, model and POP had significant differences. Nine potential biomarkers were identified by PLS-DA and variable importance for project values(VIP) based on the metabolomics. CONCLUSION The endogenous metabolites were changed by POP intervention significantly in Yin-deficiency rats, and the preventive role may be related to the synergism of glucose and lipid metabolism, amino acid metabolism, energy metabolism with the multi-targets, which provides a basis for further study of the mechanism of POP treatment of Yin-deficiency.
关键词
玉竹 /
多糖 /
阴虚 /
气相色谱-质谱 /
代谢组学
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Key words
Polygonatum odoratum /
polysaccharide /
Yin-deficiency /
GC-MS /
metabonomics
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中图分类号：
R969.1
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参考文献
[1] WANG B, SHEN L, CONG W J, et al. Metabonomic research on the intervention effects of Liuweidihuang Pill on hyperthyroidism Yin-deficiency rats . Chin Pharmacol Bull(中国药理学通报), 2013, 29(05):632-636.
[2] Ch.P(2015)VolⅠ(中国药典2015版.一部).2015:84-85.
[3] QUAN L T, WANG S C, ZHANG J. Chemical constituents from Polygonatum odoratum. Biochem Syst Ecol, 2015,58:281-284.
[4] ZHAO X, ZENG J, GAO H, et al. Optimization and composition of volatile oil from Polygonatum odoratum(Mill Druce) using supercritical fluid extraction. Trop J Pharm Res, 2014, 13(5):779-786.
[5] ZHANG L X, PANG W, FU J J, et al. Hypoglycemic effect study on streptozotocin induced type 1 diabetes in mice by Polygonatum odoratum. Pharmacol Clin Chin Mater Clin Med(中药药理与临床), 2012, 2(2):107-110.
[6] ZHOU X, YU P Z, ZHAO H, et al. Antioxidant homoiso flavonoids from Polygonatum odoratum. Food Chem, 2015,186:63-68.
[7] OUYANG L, CHEN Y, WANG X, et al. Polygonatum odoratum lectin induces apoptosis and autophagy via targeting EGFR-mediated Ras-Raf-MEK-ERK pathway in human MCF-7 breast cancer cells. Phytomedicine, 2014, 21(12):1658-1665.
[8] ZHAN R J, CHEN S H, LV G Y, et al. Effects of three TCM with sweet-flavor, cool-nature and meridian tropism in lung on the cAMP, cGMP of lung-yin deficiency rats. Pharmacol Clin Chin Mater Clin Med(中药药理与临床), 2012, 28(6):85-87.
[9] WANG S M, XU X Y. Efects of ziyinqingre agents on plasm a cyclic nucleotide. Chin Pharm(中国药业), 2003,12(7):26-27.
ZHANG J J, SHEN S H. Classification and distribution feature of TCM-based constitution of patients with impaired glucose tolerance:report of 400 cases. Chin Gen Pract(中国全科医学), 2013, 16(21):2527-2529.
ZHU Y B, WANG Q, DENG Q W, et al. Relationships between constitutional types of traditional Chinese medicine and hypertension. J Integr Tradit West Med(中西医结合学报), 2010, 8(1):40-45.
SONG L, WU J, LIU C X, et al. Research advance on metabonomics as a measure for safety evaluation. Chin Pharm J(中国药学杂志), 2006,41(12):881-885.
BAI J Q, CHENG Y Y. Metabolomics in drug-induced toxicity and drug metabolism. Chin Pharm J(中国药学杂志), 2005, 40(21):1601-1604.
ZHANG X L, JIN G Q, XU P C, et al. Study on effects of nourishing Yin and releasing Huo of Dabuyin Granulein rat model of Yin deficiency and Huo exuberance. Pharmacol Clin Chin Mater Clin Med(中药药理与临床), 2001, 17(1):7-8.
ESCOBAR-MORREALE H F, SAMINO S, INSENSER M, et al. Metabolic heterogeneity in polycystic ovary syndrome is determined by obesity: plasma metabolomic approach using GC-MS. Clin Chem, 2012, 58(6): 999-1009.
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基金
国家自然科学基金资助项目(81503041);教育部高等学校博士学科点专项科研基金资助(20124323120004);湖南省自然科学基金资助(13JJ4089);国家科技部公益性行业专项资助(201507002);湖南省教育厅科研优秀青年项目资助(15B170)
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