异常黑胆质成熟剂对移植性宫颈癌(U27)肿瘤模型小鼠血清的代谢组学研究
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摘要
目的建立移植性宫颈癌(U27)肿瘤小鼠模型并探讨异常黑胆质成熟剂(Abnormal Savda Munziq,ASMq)对移植性宫颈癌(U27)肿瘤模型小鼠血清代谢的影响。方法采用核磁共振氢谱(1H-NMR)技术结合模式识别和正交偏最小二乘判别法(OPLS-DA)进行分析,寻求不同剂量的ASMq以及环磷酰胺(Cyclophosphamide,CY)给药干预后移植性宫颈癌(U27)肿瘤模型小鼠血清中代谢产物的变化以及发生改变的代谢网络途径。结果与正常对照组比较,移植性宫颈癌(U27)肿瘤模型组小鼠血清中异亮氨酸、缬氨酸、丙氨酸、谷氨酰胺、甘氨酸等氨基酸及乳酸、柠檬酸、肌酸和1-甲基组氨酸等代谢物含量明显降低,而低密度脂蛋白(low density lipoprotein,LDL)含量升高,差异有统计学意义(P<0.05)。与移植性宫颈癌(U27)肿瘤模型组比较,环磷酰胺组中亮氨酸、丙氨酸等代谢物含量升高,差异有统计学意义(P<0.05)。与移植性宫颈癌(U27)肿瘤模型组比较,灌胃不同剂量ASMq之后小鼠血清中异亮氨酸、亮氨酸、缬氨酸、丙氨酸、谷氨酰胺等氨基酸含量升高及糖蛋白、柠檬酸、肌酸等代谢物含量也有升高趋势,差异有统计学意义(P<0.05)。结论 ASMq对移植性宫颈癌(U27)肿瘤模型小鼠有一定的抗肿瘤作用,其作用机制可能是不仅调节移植性宫颈癌(U27)肿瘤模型小鼠体内发生紊乱的氨基酸、能量代谢,也可以提高免疫功能,从而实现其预防与治疗肿瘤的作用。
OBJECTIVE To establish the portability cervical cancer(U27) tumor mice model and to study the influence of Abnormal Savda Munziq(ASMq) on serum metabolism of cervical cancer(U27) tumor model mice. METHODS Using Nuclear Magnetic Resonance Spectroscopy(1H-NMR) technology combined with pattern recognition and orthogonal partial least squares discriminant analysis(OPLS-DA) method analyze to seeking for the variability of serum metabolites and metabolic network pathways of cervical cancer(U27) tumor mice's after oral administration of low, medium, high dose of ASMq and cyclophosphamide drug intervention. RESULTS Compared with normal control group, the concentration level of some metabolites were reduced in the cervical cancer(U27) tumor model group mice's serum, including isoleucine, valine, alanine, glutamine, glycine, amino acid and lactic acid, citric acid, creatine and 1-methyl histidine; while low density lipoprotein level was increased(P<0.05). Compared with the cervical cancer(U27) tumor model group, leucine and alanine levels was increased in the cyclophosphamide control group(P<0.05); after oral administration the different doses of ASMq, the serum in the cervical cancer(U27) tumor model group mice's, the amino acids that isoleucine, leucine, valine, alanine, glutamine content was increased and glycoprotein, citric acid, creatine content also had a rising trend(P<0.05). CONCLUSION ASMq has some antitumor effects on cervical cancer(U27) tumor mice model, and it's mechanism of prevention and treatment of tumor may be achieved not only by adjusting the disordered amino acid metabolism and energy metabolism, but also improving the immune function of cervical cancer(U27) tumor model mice.
OBJECTIVE To establish the portability cervical cancer(U27) tumor mice model and to study the influence of Abnormal Savda Munziq(ASMq) on serum metabolism of cervical cancer(U27) tumor model mice. METHODS Using Nuclear Magnetic Resonance Spectroscopy(1H-NMR) technology combined with pattern recognition and orthogonal partial least squares discriminant analysis(OPLS-DA) method analyze to seeking for the variability of serum metabolites and metabolic network pathways of cervical cancer(U27) tumor mice's after oral administration of low, medium, high dose of ASMq and cyclophosphamide drug intervention. RESULTS Compared with normal control group, the concentration level of some metabolites were reduced in the cervical cancer(U27) tumor model group mice's serum, including isoleucine, valine, alanine, glutamine, glycine, amino acid and lactic acid, citric acid, creatine and 1-methyl histidine; while low density lipoprotein level was increased(P<0.05). Compared with the cervical cancer(U27) tumor model group, leucine and alanine levels was increased in the cyclophosphamide control group(P<0.05); after oral administration the different doses of ASMq, the serum in the cervical cancer(U27) tumor model group mice's, the amino acids that isoleucine, leucine, valine, alanine, glutamine content was increased and glycoprotein, citric acid, creatine content also had a rising trend(P<0.05). CONCLUSION ASMq has some antitumor effects on cervical cancer(U27) tumor mice model, and it's mechanism of prevention and treatment of tumor may be achieved not only by adjusting the disordered amino acid metabolism and energy metabolism, but also improving the immune function of cervical cancer(U27) tumor model mice.
引文
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[11]HASIM A,SAIMAITI A,KUERBAN S,et al.Analysis of the blood amino acid metabonomics of cervical intraepithelial neoplasia and cervical cancer by High-performance Liquid Chromatography[J].Sin Technol Rev(科技导报),2014,32(6):80-84.
[12]MA J Q,HASIMU A,MAMTIMIN B,et al.1H-NMR-based metabonomicis analysis of plasma samples with cervical intraepithelial neoplasia[J].Sin Technol Rev(科技导报),2010,28(10):36-40.
[13]MAMPASSI D M,顾月清.与肿瘤有关的氨基酸代谢缺陷及其相关药物的应用[J].药物生物技术,2012,19(4):373-376.
[14]FLARING U B,ROOYACKERS O E,WERNERMA J,et al.Glutamine attenuates post-traumatic glutathione depletion in human muscle[J].Clin Sin,2003,104(3):275-282.
[15]TURAHUN A,UPUR H,HAO F H,et al.Metabonomic studies on abnormal savda syndrome patients with neoplasm using NMR Spectroscop[J].Sin Technol Rev(科技导报),2009,27(13):27-31.
[16]XUE Q,NIE X L,LUO R,et al.1H-NMR-based metabonomics research on plasma from patients with hyperlipidemia with OPLS-DA[J].J Pract Med(实用医学杂志),2010,26(21):3874-3877.
[17]MAMTIMIN B,UPUR H.Plasma metabonomics analysis of tumor patients of phlegm-states syndrome[J].Chin J Integrat Tradit West Med(中国中西医结合杂志),2011,31(4):492-495.
[18]YAN X H,MAMTIMIN B,LI C Y,et al.Plasma metabonomics study on the asthma diagnosed as Shenxutanyu syndrome in traditional Chinese medicine with NMR[J].J Xinjiang Med Univ(新疆医科大学学报),2010,33(3):228-233.
[2]HU H H,SHENG L,UPUR H,et al.Anti-cancer effects of uighur medicine abnormal savda munzip and its influence on cell migration[J].Sin Technol Rev(科技导报),2011,29(03):62-65.
[3]AIKEMU A,BERKE B,UPUR H,et al.The impact of the Uighur medicine abnormal savda munziq on antitumor and antioxidant activity in a S180 and Ehrlich ascites carcinoma mouse tumor mode[J].Pharmacogn Mag,2012,8(30):141-148.
[4]KURBANTAY N,MAMTIMIN B,HIZBULLA M,et al.Effect of abnormal savda munziq on urine metabolites from abnormal savda syndrome carrying asthma rat model[J].J Xinjiang Med Univ(新疆医科大学学报),2013,36(4):419-426.
[5]HIZBULLA M,MAMTIMIN B,KURBANTAY N,et al.NMR metabonomic study of abnormal savda munziq`s mechanism of effect to the abnormal savda syndrom type 2diabets rats[J].J Xinjiang Med Univ(新疆医科大学学报),2013,36(4):411-418.
[6]UPUR H,MIJIT M,ISKANDAR B,et al.Effect of abnormal savda rat with hepatocarci based on serum metabonomic analysis[J].Sin Technol Rev(科技导报),2015,33(2):1-5.
[7]ABUDULA M,NUERMAIMAITI A,MOSHA G,et al.NMR metabonomics of serum in a rat model of abnormalsavda deasese carrying ulcerative colitis[J].World Chin J Digestol(世界华人消化杂志),2014,22(35):5414-5421.
[8]NICOLSON J K,LINDON J C,HOLMES E.Metabonomics:understandsing the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data[J].Xenobiotica(The fate of foreign compounds in biological systems),1999,29(11):1181-1189.
[9]ZHANG C C,SUN L X.Research progress on intracellular metabolites based on metabolomics[J].Acta Pharm Sin(药学学报),2012,47(8):978-985.
[10]FAN J,HONG J,HU J D,et al.Ion chromatography based urine amino acid profiling applied for diognosis of gastric cancer[J].Gastroneterol Res Pract,2012,doi:10.1155/2012/474907.
[11]HASIM A,SAIMAITI A,KUERBAN S,et al.Analysis of the blood amino acid metabonomics of cervical intraepithelial neoplasia and cervical cancer by High-performance Liquid Chromatography[J].Sin Technol Rev(科技导报),2014,32(6):80-84.
[12]MA J Q,HASIMU A,MAMTIMIN B,et al.1H-NMR-based metabonomicis analysis of plasma samples with cervical intraepithelial neoplasia[J].Sin Technol Rev(科技导报),2010,28(10):36-40.
[13]MAMPASSI D M,顾月清.与肿瘤有关的氨基酸代谢缺陷及其相关药物的应用[J].药物生物技术,2012,19(4):373-376.
[14]FLARING U B,ROOYACKERS O E,WERNERMA J,et al.Glutamine attenuates post-traumatic glutathione depletion in human muscle[J].Clin Sin,2003,104(3):275-282.
[15]TURAHUN A,UPUR H,HAO F H,et al.Metabonomic studies on abnormal savda syndrome patients with neoplasm using NMR Spectroscop[J].Sin Technol Rev(科技导报),2009,27(13):27-31.
[16]XUE Q,NIE X L,LUO R,et al.1H-NMR-based metabonomics research on plasma from patients with hyperlipidemia with OPLS-DA[J].J Pract Med(实用医学杂志),2010,26(21):3874-3877.
[17]MAMTIMIN B,UPUR H.Plasma metabonomics analysis of tumor patients of phlegm-states syndrome[J].Chin J Integrat Tradit West Med(中国中西医结合杂志),2011,31(4):492-495.
[18]YAN X H,MAMTIMIN B,LI C Y,et al.Plasma metabonomics study on the asthma diagnosed as Shenxutanyu syndrome in traditional Chinese medicine with NMR[J].J Xinjiang Med Univ(新疆医科大学学报),2010,33(3):228-233.