高级搜索

活性肽调节肿瘤细胞代谢途径的研究进展

李伟欣, 龚维, 吴磊燕, 穆利霞, 邹宇晓, 廖森泰

李伟欣, 龚维, 吴磊燕, 穆利霞, 邹宇晓, 廖森泰. 活性肽调节肿瘤细胞代谢途径的研究进展[J]. 肿瘤防治研究, 2017, 44(6): 428-432. DOI: 10.3971/j.issn.1000-8578.2017.16.1611
引用本文: 李伟欣, 龚维, 吴磊燕, 穆利霞, 邹宇晓, 廖森泰. 活性肽调节肿瘤细胞代谢途径的研究进展[J]. 肿瘤防治研究, 2017, 44(6): 428-432. DOI: 10.3971/j.issn.1000-8578.2017.16.1611
LI Weixin, GONG Wei, WU Leiyan, MU Lixia, ZOU Yuxiao, LIAO Sentai. Research Progress of Active Peptides Regulating Tumor Cells Metabolic Pathways[J]. Cancer Research on Prevention and Treatment, 2017, 44(6): 428-432. DOI: 10.3971/j.issn.1000-8578.2017.16.1611
Citation: LI Weixin, GONG Wei, WU Leiyan, MU Lixia, ZOU Yuxiao, LIAO Sentai. Research Progress of Active Peptides Regulating Tumor Cells Metabolic Pathways[J]. Cancer Research on Prevention and Treatment, 2017, 44(6): 428-432. DOI: 10.3971/j.issn.1000-8578.2017.16.1611

活性肽调节肿瘤细胞代谢途径的研究进展

基金项目: 

国家自然科学基金 31401643

国家现代农业产业技术体系建设专项资金 CARS-22-ZJ0501

广东省省级科技计划项目 2013B090600060

详细信息
    作者简介:

    李伟欣(1991-),男,硕士在读,主要从事活性肽抗肿瘤研究

    通讯作者:

    吴磊燕,E-mail: fswuly@163.com

    穆利霞,E-mail: lisa1980119@126.com

  • 中图分类号: R730.1

Research Progress of Active Peptides Regulating Tumor Cells Metabolic Pathways

More Information
  • 摘要:

    生物活性肽具有多种生物学功能,可特异性作用于恶性肿瘤,与其生长转移相关的信号转导分子相互作用,抑制肿瘤生长或促进肿瘤细胞凋亡。本文从活性肽对STAT3信号通路的调节、对TRAIL死亡受体信号通路的调控、PKM2调节有氧糖酵解以及对NF-кB信号通路的调控来抑制肿瘤细胞生长代谢等几个方面进行概述,为寻找更明确更具有针对性的抗肿瘤活性肽类药物提供参考。

     

    Abstract:

    Bioactive peptides have a variety of biological functions. They can influence malignant tumor specifically, interact with signal transduction molecule aboutgrowth and metastasis, and inhibit the growth of tumourcells or accelerate the apoptosis. In order to provide a reference for researching the more purposeful anti-tumor bioactive peptides, this paper will overview the research progress of active peptides regulating tumor cells metabolic pathways from STAT3 signalpathway, TRAIL death receptor pathway, PKM2aerobic glycoysisand NF-кB signalpathway.

     

  • 宫颈小细胞神经内分泌癌(small cell neuroendocrine carcinoma, SCNEC)是一种较为罕见的原发于宫颈的神经内分泌性肿瘤,约占宫颈恶性肿瘤的1%~2%[1-2]。在各种类型的宫颈癌中,SCNEC是一种侵袭性强的病理类型[3-8]。但因为该类病例较少,目前尚无规范化的治疗。本研究对101例宫颈小细胞神经内分泌癌患者的临床病理资料及生存状况进行分析,旨在探讨SCNEC合理的治疗方案及预后相关因素,为此类患者治疗及预后判断提供临床依据。

    收集2007年1月—2018年6月在江西省妇幼保健院确诊并完成治疗的101例宫颈小细胞神经内分泌癌患者作为研究对象。患者确诊年龄25~73岁,中位年龄44岁,其中41~50岁者有40例。宫颈局部肿瘤直径 > 4 cm患者34例,≤4 cm患者67例。患者临床资料及年龄分布见表 1。所有患者均知情同意。

    表  1  101例SCNEC患者临床病理特征
    Table  1  Clinical and pathological features of 101 SCNEC patients
    下载: 导出CSV 
    | 显示表格

    (1)所有患者接受治疗前均经江西省妇幼保健院病理确诊为宫颈小细胞神经内分泌癌;(2)临床分期盆腔检查均经三位以上有经验的妇科肿瘤专业医师检查确定;(3)治疗前均未接受任何干预性治疗,且初始治疗及后续治疗均在同一机构完成;(4)纳入研究的患者治疗模式均为手术+术后补充放化疗(下文简称手术治疗组)或根治性放化疗,且按计划完成全部治疗;(5)全部患者术后病理检查均在同一医院完成;(6)建立了完整的病历档案,并持续随访,具备完整的住院及门诊复查病历资料。

    72例手术治疗患者手术方式为广泛子宫切除+盆腔淋巴结切除术±腹主动脉旁淋巴结切除术,其中47例行腹主动脉旁淋巴结切除术。69例行双附件切除,其余3例保留一侧卵巢且进行了保留卵巢的组织活检。

    放疗包括体外照射+腔内后装治疗,体外照射采用全盆腔体外照射+中央遮盖体外照射。体外照射剂量:全盆照射肿瘤剂量30~40 Gy,中央遮盖照射剂量15~25 Gy,放疗频率及强度:每周5次,每次分割剂量2 Gy。腔内后装采用高剂量率后装治疗设备,放射源为铱192。放疗剂量参照点A点累积剂量要求60~70 Gy;B点累积剂量要求54~56 Gy。放疗期间均给予铂类为基础的同步化疗。

    通过电话或门诊复查方式进行随访,截止时间为2018年9月。

    采用GraphPad7.0统计软件对不同组间患者生存率进行显著性比较。生存分析采用Kaplan-Meier法,生存率的比较采用Log rank检验。P < 0.05为差异有统计学意义。

    72例手术组患者中,2例失访,19例死亡,51例生存。19例死亡患者生存时间1~63月,中位生存时间19月,平均生存时间18.5月。51例生存的患者中,生存时间1~139月,中位生存时间39月,平均生存时间47.3月。随访5年以上共33例,生存20例,五年生存率60.6%。

    29例根治性放化疗患者中,随访5年以上20例,其中2例失访,死亡15例,生存3例,五年生存率15%。生存时间1~75月,中位生存时间21月。3例生存患者年龄分别为40岁、41岁、46岁,临床分期均为ⅡB期,病理均为单纯的宫颈小细胞神经内分泌癌,化疗方案均为多西他赛+卡铂,放疗给予根治性同步放化疗。ⅠB1期~ⅡA期手术治疗组患者生存率优于ⅡB期~Ⅳ期期根治性放化疗组患者(P=0.0025),见图 1

    图  1  手术组与放化疗组患者生存曲线图
    Figure  1  Survival curves of Surgery and CCRT groups

    72例接受手术治疗的患者均行宫颈癌根治术+盆腔淋巴结切除术,47例行腹主动脉旁淋巴结切除术,其中1例(1/47, 2.12%)腹主动脉旁淋巴结阳性。27例(27/72, 37.5%)盆腔淋巴结阳性。淋巴结阳性与阴性患者生存曲线比较差异有统计学意义,淋巴结阴性患者生存优于淋巴结阳性患者(P=0.0004),见图 2

    图  2  盆腔淋巴结阳性和阴性手术患者生存曲线
    Figure  2  Survival curves of surgical SCNEC patients with pelvic lymph node positive and negative

    72例手术治疗的患者中,按病理类型分,单纯SCNEC例41例,混合其他病理类型者31例,其中混合有腺癌19例,鳞癌9例,腺鳞癌3例。混合型与单纯型SCNEC生存曲线比较差异无统计学意义(P=0.0546),见图 3

    图  3  单纯型与混合型SCNEC生存曲线
    Figure  3  Survival curves of pure and mixed type SCNEC patients

    WHO分类将宫颈神经内分泌肿瘤分为低级别神经内分泌肿瘤(包括类癌及非典型类癌)和高级别神经内分泌肿瘤(包括小细胞神经内分泌癌和大细胞神经内分泌癌)。目前无公认的、规范有效的治疗方案,对于宫颈神经内分泌肿瘤多参照常见宫颈癌的分期治疗原则,主张手术、化疗和放疗的综合性治疗,但其治疗是否应有别于宫颈鳞癌需要更大样本、多中心的研究。美国国立综合癌症网络(National Comprehensive Cancer Network, NCCN)指南也将SCNEC列入特殊类型宫颈癌。

    关于SCNEC患者生存率及预后方面的研究,Ishikawa等的一项多中心研究显示淋巴血管间隙受侵是患者的总生存率及无进展生存率的重要预后因素,盆腔淋巴结转移是DFS的重要预后影响因素[9]。Cohen等研究发现Ⅰ~ⅡA、ⅡB~ⅣA、ⅣB期5年生存率分别为36.8%、9.8%和0[10],本研究结果显示临床分期与预后密切相关,各期别5年生存率均较以往文献报道略高。FIGO分期是较为公认的影响患者预后的最重要的独立危险因素[11-12]。由于SCNEC侵袭性强,易发生远处转移,有学者认为早期SCNEC患者手术联合化疗的预后优于单纯手术者[13-14]。本研究中ⅠB~ⅡA期患者均采用手术+放化疗综合治疗,5年总生存率60%以上,提示手术联合术后放化疗对此类患者疗效较好。

    宫颈小细胞神经内分泌癌早期容易发生转移,但从72例早期患者手术情况发现,仅1例(1.39%)发生卵巢转移。提示对于存在生育要求的年轻SCNEC患者,是否一定要行卵巢切除有待进一步研究证实。研究证实,SCNEC好发转移器官为肺、脑、肝,预后差[15-16]

    此外,几乎所有文献均支持此类肿瘤早期即容易发生远处转移,本研究资料中,死亡病例主要病因为肺转移、全身转移,临床观察也支持上述观点。关于淋巴结转移,有研究认为,即使是早期的SCNEC患者,淋巴结转移也非常普遍,淋巴结转移率为41.6%~57%[17]。本研究中,72例早期SCNEC患者手术后病理提示淋巴结转移22例,转移率37.5%,与文献报道接近,但是对于腹主动脉旁淋巴结,72例患者中47例患者行腹主动脉旁淋巴结活检或切除,仅1例发生腹主动脉旁淋巴结转移,转移率仅为2.13%,远低于盆腔淋巴结转移率。这一研究结果提示我们,即便是早期SCNEC患者,化疗对于控制转移也有重要的临床意义。

    与以往报道相比,本研究中手术患者术后均补充了放化疗,且均达到6个疗程,其中49例采用紫杉醇+铂类化疗方案,23例采用顺铂+环磷酰胺+表阿霉素化疗方案,提示手术后放化疗的必要性。

    总之,宫颈小细胞神经内分泌癌发病率低、恶性程度高、易发生远处转移和复发,患者预后差、死亡率高、有独特的病理特征,诊断主要依据病理诊断和免疫组织化学结果可提高其诊断的准确率。由于研究样本少,尚需大量的临床资料及多中心研究探索最佳早期诊断及治疗的方法。

  • [1]

    Mayevsky A. Mitochondrial function and energy metabolism in cancer cells: past overview and future perspectives[J]. Mitochondrion, 2009, 9(3): 165-79. doi: 10.1016/j.mito.2009.01.009

    [2]

    Kroemer G, Pouyssegur J. Tumor cell metabolism: cancer's Achilles' heel[J]. Cancer Cell, 2008, 13(6): 472-82. doi: 10.1016/j.ccr.2008.05.005

    [3]

    Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism[J]. Nat Rev Cancer, 2011, 11(2): 85-95. doi: 10.1038/nrc2981

    [4]

    Loud JT, Peters JA, Fraser M, et al. Applications of advances in molecular biology and genomics to clinical cancer care[J]. Cancer Nurs, 2002, 25(2): 110-22. doi: 10.1097/00002820-200204000-00007

    [5]

    Giessen TW, Marahiel MA. Ribosome-independent biosynthesis of biologically active peptides: Application of synthetic biology to generate structural diversity[J]. FEBS Lett, 2012, 586(15): 2065-75. doi: 10.1016/j.febslet.2012.01.017

    [6]

    Cheong SH, Kim EK, Hwang JW, et al. Purification of a novel peptide derived from a shellfish, Crassostrea gigas, and evaluation of its anticancer property[J]. J Agric Food Chem, 2013, 61(47): 11442-6. doi: 10.1021/jf4032553

    [7]

    Lv S, Gao J, Liu T, et al. Purification and partial characterization of a new antitumor protein from Tegillarca granosa[J]. Mar Drugs, 2015, 13(3): 1466-80. doi: 10.3390/md13031466

    [8]

    Martincuks A, Fahrenkamp D, Haan S, et al. Dissecting functions of the N-terminal domain and GAS-site recognition in STAT3 nuclear trafficking[J]. Cell Signal, 2016, 28(8): 810-25. doi: 10.1016/j.cellsig.2016.03.011

    [9]

    Yan W, Fan W, Chen C, et al. IL-15 up-regulates the MMP-9 expression levels and induces inflammatory infiltration of macrophages in polymyositis through regulating the NF-κB pathway[J]. Gene, 2016, 591(1): 137-47. doi: 10.1016/j.gene.2016.06.055

    [10]

    Alenzi FQ. The significance and occurrence of TNF receptor polymorphisms in the Saudi population[J]. Saudi J Biol Sci, 2016, 23(6): 767-72. doi: 10.1016/j.sjbs.2016.04.015

    [11]

    Hou Y, Nie Y, Cheng B, et al. Qingfei Xiaoyan Wan, a traditional Chinese medicine formula, ameliorates Pseudomonas aeruginosa -induced acute lung inflammation by regulation of PI3K/AKT and Ras/MAPK pathways[J]. Acta Pharm Sin B, 2016, 6(3): 212-21. doi: 10.1016/j.apsb.2016.03.002

    [12]

    Bi CL, Wang H, Wang YJ, et al. Selenium inhibits Staphylococcus aureus -induced inflammation by suppressing the activation of the NF-κB and MAPK signalling pathways in RAW264.7 macrophages[J]. Eur J Pharmacol, 2016, 780: 159-65. doi: 10.1016/j.ejphar.2016.03.044

    [13]

    Erkasap N, Özyurt R, Özkurt M, et al. The role of JAK/STAT signaling pathway and TNF-α crosstalk in human colorectal cancer[J]. Gene Reports, 2016, 3: 1-4. doi: 10.1016/j.genrep.2016.01.002

    [14]

    Papatriantafyllou M. Gene regulation: STATs control subset-specific enhancer activation[J]. Nat Rev Immunol, 2013, 13(1): 7. http://www.nature.com/articles/doi:10.1038%2Fnri3381

    [15]

    Zare F, Dehghan-Manshadi M, Mirshafiey A. The signal transducer and activator of transcription factors lodge in immunopathogenesis of rheumatoid arthritis[J]. Reumatismo, 2015, 67(4): 127-37.

    [16]

    Przanowski P, Dabrowski M, Ellert-Miklaszewska A, et al. The signal transducers Stat1 and Stat3 and their novel target Jmjd3 drive the expression of inflammatory genes in microglia[J]. J Mol Med(Berl), 2014, 92(3): 239-54. https://www.researchgate.net/profile/Jan_Komorowski2/publication/257463940_The_signal_transducers_STAT1_and_STAT3_and_their_novel_target_JMJD3_drive_the_expression_of_inflammatory_genes_in_microglia/links/0c9605322bbc64ba8a000000.pdf

    [17]

    Kuang S, Qi C, Liu J, et al. 2-Methoxystypandrone inhibits signal transducer and activator of transcription 3 and nuclear factor-κB signaling by inhibiting Janus kinase 2 and IκB kinase[J]. Cancer Sci, 2014, 105(4): 473-80. doi: 10.1111/cas.2014.105.issue-4

    [18]

    Nelson EA, Sharma SV, Settleman J, et al. A chemical biology approach to developing STAT inhibitors: molecular strategies for accelerating clinical translation[J]. Oncotarget, 2011, 2(6): 518-24. doi: 10.18632/oncotarget

    [19]

    Barbieri I, Pensa S, Pannellini T, et al. Constitutively active Stat3 enhances neu-mediated migration and metastasis in mammary tumors via upregulation of Cten[J]. Cancer Res, 2010, 70(6): 2558-67. doi: 10.1158/0008-5472.CAN-09-2840

    [20]

    Fletcher S, Turkson J, Gunning PT. Molecular Approaches towards the Inhibition of the Signal Transducer and Activator of Transcription 3 (Stat3) Protein[J]. Chem Med Chem, 2008, 3(3): 1159-68. https://www.researchgate.net/publication/23152137_Molecular_Approaches_towards_the_Inhibition_of_the_Signal_Transducer_and_Activator_of_Transcription_3_Stat3_Protein

    [21]

    Turkson J, Ryan D, Kim JS, et al. Phosphotyrosyl peptides block Stat3-mediated DNA binding activity, gene regulation, and cell transformation[J]. J Biol Chem, 2001, 276(48): 45443-55. doi: 10.1074/jbc.M107527200

    [22]

    Nagel-Wolfrum K, Buerger C, Wittig I, et al. The interaction of specific peptide aptamers with the DNA binding domain and the dimerization domain of the transcription factor Stat3 inhibits transactivation and induces apoptosis in tumor cells[J]. Mol Cancer Res, 2004, 2(3): 170-82. http://mcr.aacrjournals.org/content/molcanres/2/3/170.full.pdf

    [23]

    Borghouts C, Kunz C, Delis N, et al. Monomeric recombinant peptide aptamers are required for efficient intracellular uptake and target inhibition[J]. Mol Cancer Res, 2008, 6(2): 267-81. doi: 10.1158/1541-7786.MCR-07-0245

    [24]

    Abdelsalam RM, Safar MM. Neuroprotective effects of vildagliptin in rat rotenone Parkinson's disease model: role of RAGE-NFκB and Nrf2-antioxidant signaling pathways[J]. J Neurochem, 2015, 133(5): 700-7. doi: 10.1111/jnc.2015.133.issue-5

    [25]

    Barnhart BC, Alappat EC, Peter ME. The CD95 typeⅠ/type Ⅱ model[J]. Semin Immunol, 2003, 15(3): 185-93. doi: 10.1016/S1044-5323(03)00031-9

    [26]

    Carrillo I, Droguett D, Castillo C, et al. Caspase-8 activity is part of the BeWo trophoblast cell defense mechanisms against Trypanosoma cruzi infection[J]. Exp Parasitol, 2016, 168: 9-15. doi: 10.1016/j.exppara.2016.06.008

    [27]

    Mahmood Z, Shukla Y, Death receptors: targets for cancer therapy[J]. Exp Cell Res, 2010, 316(6): 887-99. doi: 10.1016/j.yexcr.2009.12.011

    [28]

    Wilson NS, Yang A, Yang B, et al. Proapoptotic activation of death receptor 5 on tumor endothelial cells disrupts the vasculature and reduces tumor growth[J]. Cancer Cell, 2012, 22(1): 80-90. doi: 10.1016/j.ccr.2012.05.014

    [29] 林婷婷. TRAIL联合谷胱甘肽过氧化物酶模拟物治疗乳腺癌的实验研究[D]. 吉林: 吉林大学, 2010.

    Lin TT. Experimental study on treatment of human breast cancer cells with combination of TRAIL and glutathione peroxidase mimics[D]. Jilin: Jilin Da Xue, 2010.

    [30]

    Diaz-Ruiz R, Rigoulet M, Devin A. The Warburg and Crabtree effects: On the origin of cancer cell energy metabolism and of yeast glucose repression[J]. Biochim Biophys Acta, 2010, 1807(6): 568-76. http://d.scholar.cnki.net/detail/SJES_U/SJES13011701997687

    [31]

    Koppenol WH, Bounds PL, Dang CV. Otto Warburg's contributions to current concepts of cancer metabolism[J]. Nat Rev Cancer, 2011, 11(5): 325-37. doi: 10.1038/nrc3038

    [32]

    Mazurek S. Pyruvate kinase type M2: a key regulator of the metabolic budget system in tumor cells[J]. Int J Biochem Cell Biol, 2010, 43(7): 969-80. https://www.researchgate.net/publication/41435022_Pyruvate_kinase_type_M2_A_key_regulator_of_the_metabolic_budget_system_in_tumor_cells

    [33]

    Anastasiou D, Poulogiannis G, Asara JM, et al. Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses[J]. Science, 2011, 334(6060): 1278-83. doi: 10.1126/science.1211485

    [34]

    Guo D, Gu J, Jiang H, et al. Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to the development of pulmonary arterial hypertension[J]. J Mol Cell Cardiol, 2016, 91: 179-87. doi: 10.1016/j.yjmcc.2016.01.009

    [35]

    Sadri H, Giallongo F, Hristov AN, et al. Effects of slow-release urea and rumen-protected methionine and histidine on mammalian target of rapamycin (mTOR) signaling and ubiquitin proteasome-related gene expression in skeletal muscle of dairy cows[J]. J Dairy Sci, 2016, 99(8): 6702-13. doi: 10.3168/jds.2015-10673

    [36]

    Luo W, Semenza GL. Pyruvate kinase M2 regulates glucose metabolism by functioning as a coactivator for hypoxia-inducible factor 1 in cancer cells[J]. Oncotarget, 2011, 2(7): 551-6. doi: 10.18632/oncotarget

    [37]

    Gao X, Wang H, Yang JJ, et al. Pyruvate kinase M2 regulates gene transcription by acting as a protein kinase[J]. Mol Cell, 2012, 45(5): 598-609. doi: 10.1016/j.molcel.2012.01.001

    [38]

    Visekruna A, Volkov A, Steinhoff U. A key role for NF-κB transcription factor c-Rel in T-lymphocyte-differentiation and effector functions[J]. Clin Dev Immunol, 2012, 2012: 239368. https://www.researchgate.net/publication/223963393_A_Key_Role_for_NF-kB_Transcription_Factor_c-Rel_in_T-Lymphocyte-Differentiation_and_Effector_Functions

    [39]

    Park JM, Greten FR, Wong A, et al. Signaling pathways and genes that inhibit pathogen-induced macrophage apoptosis-CREB and NF-kappaB as key regulators[J]. Immunity, 2005, 23(3): 319-29. doi: 10.1016/j.immuni.2005.08.010

    [40]

    Yamamoto Y, Gaynor RB. IkappaB kinases: key regulators of the NF-kappaB pathway[J]. Trends Biochem Sci, 2004, 29(2): 72-9. doi: 10.1016/j.tibs.2003.12.003

    [41]

    Fili A. Business angel-venture negotiation in the post-investment relationship: the use of the good cop, bad cop strategy[J]. Venture Capital, 2015, 16(4): 309-25. https://www.researchgate.net/publication/273103049_Business_angel-venture_negotiation_in_the_post-investment_relationship_the_use_of_the_good_cop_bad_cop_strategy

    [42] 蒋伟, 王正国, 赖西南.感觉神经肽SP在伤口愈合细胞因子网络调控中的作用[J].创伤外科杂志, 2002, 4(4): 250-2. http://www.cnki.com.cn/Article/CJFDTOTAL-CXWK200204029.htm

    Jiang W, Wang ZG, Lai XN. Effects of neuropeptide substance P on cellular factor net in wound healing[J]. Chuang Shang Wai Ke Za Zhi, 2002, 4(4): 250-2. http://www.cnki.com.cn/Article/CJFDTOTAL-CXWK200204029.htm

    [43]

    Lieb K, Fiebich BL, Berger M, et al. The neuropeptide substance P activates transcription factor NF-kappa B and kappa B-dependent gene expression in human astrocytoma cells[J]. J Immunol, 1997, 159(10): 4952-8.

    [44]

    Shahrokhi S, Ebtekar M, Alimoghaddam K, et al. Substance P and calcitonin gene-related neuropeptides as novel growth factors for ex vivo expansion of cord blood CD34(+) hematopoietic stem cells[J]. Growth Factors, 2009, 28(1): 66-73. http://en.journals.sid.ir/Supporting.aspx?ID=178639

    [45] 袁平戈, 张大志.还原型谷胱甘肽的作用机制及临床应用[J].药品评价, 2006, 3(5): 385-90. http://www.cnki.com.cn/Article/CJFDTOTAL-YYXK201309313.htm

    Yuan PG, Zhang DZ. The mechanism and clinical application of reduced glutathione[J]. Yao Pin Ping Jia, 2006, 3(5): 385-90. http://www.cnki.com.cn/Article/CJFDTOTAL-YYXK201309313.htm

    [46]

    Radosavljević T, Mladenović D, Vucević D, et al. The role of oxidative/nitrosative stress in pathogenesis of paracetamol-induced toxic hepatitis[J]. Med Pregl, 2011, 63(11-12): 827-32. http://www.oalib.com/paper/2380390

    [47] 赵兵, 张华茹, 李海明, 等.还原型谷胱甘肽对大鼠不同潮气量机械通气NF-κB、TNF-α蛋白表达影响[J].中国现代医学杂志, 2008, 18(13): 1853-5. doi: 10.3969/j.issn.1005-8982.2008.13.016

    Zhao B, Zhang HR, Li HM, et al. Effects of reduced glutathione on TNF-α, NF-κB expression on different tidal volume mechanical ventilation in rats[J]. Zhongguo Xian Dai Yi Xue Za Zhi, 2008, 18(13): 1853-5. doi: 10.3969/j.issn.1005-8982.2008.13.016

    [48] 谢书越. 蚕蛹蛋白酶解产物的抗氧化活性和功能特性研究: "食品工业新技术与新进展"学术研讨会暨2014年广东省食品学会年会论文集[C]. 广州: 2014.

    Xie SY. Antioxidant Activities and Functional Properties of the Hydrolysates of Silkworm Pupae(Bombyx mori)Protein: Proceedings of symposium on new technology and new progress of food industry and annual meeting of Guang Dong Institute of Food Science and Technology in 2014[C]. Guangzhou: 2014.

    [49] 谢书越. 蚕蛹蛋白酶解产物抗氧化和抑制肿瘤增殖活性研究[D]. 湛江: 广东海洋大学, 2015.

    Xie SY. Antioxidant and tumor growth inhibition activity of peptides prepared from silkworm pupae protein[D]. Zhanjiang: Guang Dong Hai Yang Da Xue, 2015.

计量
  • 文章访问数:  1492
  • HTML全文浏览量:  320
  • PDF下载量:  814
  • 被引次数: 0
出版历程
  • 收稿日期:  2016-12-27
  • 修回日期:  2017-02-07
  • 网络出版日期:  2024-01-12
  • 刊出日期:  2017-06-24

目录

/

返回文章
返回
x 关闭 永久关闭