消痰散结方对荷瘤大鼠蛋白质代谢影响的实验研究
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
背景
     代谢异常是恶性肿瘤重要并发症,是恶性肿瘤治疗困难、预后不佳的原因之一。改善代谢异常是提高患者生存质量的治疗关键。魏品康教授提出肿瘤“痰污染”假说,认为代谢异常的物质基础是痰。现代研究已证实肿瘤蛋白质代谢异常与炎性因子有关。我科以“消痰散结”为法则,创立消痰散结方应用于恶性肿瘤的临床治疗,取得了令人满意的疗效。因此,本实验通过观察消痰散结方对荷瘤大鼠炎性因子表达的调节作用,探讨消痰散结方调整恶性肿瘤蛋白质代谢异常的可能机制。
     目的
     通过建立Wistar大鼠皮下移植Walker256瘤模型,构建恶性肿瘤痰污染环境,运用ELISA、EnVision、实时PCR等方法,检测消痰散结方对痰浊中TNF-α、IL-6等炎性因子蛋白和mRNA表达的调控作用,探讨消痰散结方调整恶性肿瘤蛋白质代谢异常的作用机制,佐证肿瘤痰证理论的科学性以及肿瘤代谢异常的痰污染环境“痰浊”的物质存在性。
     方法
     30只Wistar大鼠,随机分为正常对照组、空白组、消痰散结方组;除正常对照组外,其余各组为荷瘤大鼠,皮下接种Walker256瘤,建立大鼠蛋白质代谢异常模型。24h后消痰散结方组灌胃给药(2ml/天,×4w);正常对照组、空白组大鼠同期、同条件下一般饮食饲养;观察实验动物体重变化;第4周实验结束时,麻醉解剖所有动物,心脏取血后检测血清总蛋白、白蛋白水平,ELISA法检测血清TNF-α、IL-6表达。取胫骨前肌组织、肝组织行Envision、实时PCR等方法检测其中TNF-αIL-6、NF-Kb、泛素等的蛋白和mRNA表达。
     结果
     1.成功建立大鼠Walker256皮下移植瘤模型。移植术后7天左右可在皮下触及较硬肿块,后肿块逐渐增大。荷瘤鼠逐渐出现皮毛干枯、少食、消瘦、倦怠乏力、行动迟缓等衰竭症状。HE染色证实荷瘤鼠骨骼肌结构紊乱。
     2.荷瘤鼠因肿瘤而影响机体的正常生长,造模7天后各荷瘤鼠组体重增加值低于正常组(P<0.05);造模21天后消痰散结方组体重增加值高于空白组(P<0.05)而低于正常对照组(P<0.05)。
     3.消痰散结方对血清总蛋白和白蛋白的影响:与正常组相比,空白组、消痰散结方组总蛋白未见明显降低(P>0.05);各荷瘤鼠组白蛋白均较正常组有所下降(P<0.05),消痰散结方组高于空白组(P<0.05)。
     4.消痰散结方对血清TNF-α蛋白表达的影响:各荷瘤鼠组血清中TNF-α蛋白表达均较正常对照组明显升高(P<0.05);消痰散结方组血清TNF-α蛋白明显低于空白组(P<0.05)
     消痰散结方对血清IL-6蛋白表达的影响:各荷瘤鼠组血清中IL-6蛋白表达均较正常对照组明显升高(P<0.05);消痰散结方组血清IL-6蛋白明显低于空白组(P<0.05)。
     5.消痰散结方对肌肉组织TNF-α蛋白表达的影响:各荷瘤鼠组肌肉组织中TNF-a蛋白表达较正常对照组均明显升高(P<0.05);消痰散结方组与空白组未见明显统计学差异(P>0.05)。
     消痰散结方对肌肉组织TNF-αmRNA表达的影响:各荷瘤鼠组肌肉组织中TNF-αmRNA表达较正常对照组均明显升高(P<0.05);消痰散结方组与空白组未见明显统计学差异(P>0.05)。
     消痰散结方对肝脏组织TNF-α蛋白表达的影响:各荷瘤鼠组肝脏组织中TNF-α蛋白表达较正常对照组均明显升高(P<0.05);消痰散结方组低于空白组(P<0.05)。
     消痰散结方对肝脏组织TNF-αmRNA表达的影响:各荷瘤鼠组肝脏组织中TNF-αmRNA表达较正常对照组均明显升高(P<0.05);消痰散结方组低于空白组(P<0.05)
     6.消痰散结方对肌肉组织IL-6蛋白表达的影响:各荷瘤鼠组肌肉组织中IL-6蛋白表达较正常对照组均明显升高(P<0.05);消痰散结方组与空白组差异无统计学意义(P>0.05)
     消痰散结方对肌肉组织IL-6 mRNA表达的影响:各荷瘤鼠组肌肉组织中IL-6 mRNA表达较正常对照组均明显升高(P<0.05);消痰散结方组与空白组差异无统计学意义(P>0.05)
     消痰散结方对肝脏组织IL-6蛋白表达的影响:各荷瘤鼠组肝脏组织中TNF-α蛋白表达较正常对照组均明显升高(P<0.05);消痰散结方组低于空白组(P<0.05)。
     消痰散结方对肝脏组织IL-6 mRNA表达的影响:各荷瘤鼠组肝脏组织中TNF-a mRNA表达较正常对照组均明显升高(P<0.05);消痰散结方组低于空白组(P<0.05)。
     7.消痰散结方对肌肉组织NF-Kb蛋白表达的影响:各荷瘤鼠组肌肉组织中NF-Kb蛋白表达较正常对照组均明显升高(P<0.05);消痰散结方组与空白组差异无统计学意义(P>0.05)
     消痰散结方对肌肉组织NF-Kb mRNA表达的影响:各荷瘤鼠组肌肉组织中NF-Kb mRNA表达较正常对照组均明显升高(P<0.05);消痰散结方组与空白组差异无统计学意义(P>0.05)。
     8.消痰散结方对肌肉组织泛素蛋白表达的影响:各荷瘤鼠组肌肉组织中泛素蛋白表达较正常对照组均明显升高(P<0.05);消痰散结方组低于空白组(P<0.05)。
     消痰散结方对肌肉组织泛素mRNA表达的影响:各荷瘤鼠组肌肉组织中泛素mRNA表达较正常对照组均明显升高(P<0.05);消痰散结方组低于空白组(P<0.05)。
     结论
     1.建立的大鼠Walker256皮下移植瘤模型,制作方法简单,成瘤率高,具有与临床恶性肿瘤代谢异常类似的表现。
     2.消痰散结方可提高荷瘤大鼠的体重及血清白蛋白水平。
     3.荷瘤鼠血清、肌肉组织、肝脏组织中rNF-α、IL-6等炎性因子表达升高,证实炎性因子与肿瘤蛋白质代谢异常密切相关,
     4.消痰散结方可下调荷瘤大鼠肝脏组织中TNF-α、IL-6等炎性因子的表达,调控肝脏的蛋白合成,下调荷瘤大鼠肌肉组织中泛素的表达,调控骨骼肌ATP-泛素蛋白酶体途径,是其清化肿瘤痰污染环境,改善肿瘤代谢异常的可能机制之一。同时证明了肿瘤痰污染假说的科学性、“痰”的物质存在性。
Background:
     Metabolic abnormalities which are the important complications of malignant tumor are one of the reasons for difficult treatment and bad prognosis. Adjusting metabolic abnormalities is the key to elevate patients'survival quality. Phlegm pollution hypothesis proposed by Professor Wei-Pinkang is said that the reason for metabolic abnormalities is muddy phlegm. It is already confirmed that tumor protein metabolic abnormalities are relevant to inflammation. Prof. Wei has established his theory of "dispersing phlegm and dissipating bind" in clinically treating patients with tumors. Therapeutic effect is satisfactory. So the purpose of this study is to discover the mechanism of Xiaotan Sanjie Decoction adjusting tumor protein metabolic abnormalities in a more comprehensive and convincing way by regulating the expressions of different inflammatory factors in the tumor-bearing rats.
     Objective:
     The study was designed to investigate the mechanism of Xiaotan Sanjie Decoction in tumor protein metabolic abnormalities and prove scientific nature of the theory of tumor phlegm syndrome and material existence of environment polluted by phlegm "muddy phlegm" promoting the tumor metabolic abnormalities. To construct environment polluted by phlegm by establishing subcutaneous model of Carcinosarcome Walker 256 in Wistar rats and by the methods of ELISA, Envision, realtime-PCR to detect the expressions of inflammatory factors'(TNF-a, IL-6, ect) mRNA and encoded protein regulated by Xiaotan Sanjie Decoction.
     Methods:
     30 Wistar mice were randomly divided into normal group, no-drugs group and Xiaotan Sanjie Decoction group. The rats were made subcutaneous model of Carcinosarcome Walker 256 except the rats in normal group to establish tumor protein metabolic abnormalities model. The rats in Xiaotan Sanjie Decoction group were applied with herbs 24 hours after the surgery (2ml/d,×4w); normal group and no-drugs group were raised in the same condition and with common food and drink. The weight was observed. The experiment was terminated on the 4th week.The rats were sacrificed after blood sampling collected from heart. The total protein and albumin were detected. The expressions of mRNA and encoded protein of TNF-a, IL-6, NF-Kb and Ubiquitin were detected by the methods of ELISA, Envision and Realtime-PCR.
     Results:
     1. We built subcutaneous model of Carcinosarcome Walker 256, the lump could be touched in the Subcutaneous 7 days after modeling and increas gradually. Rats bearing tumor emerged exhausted symptoms of dried-up coat, less food, athrepsy, lassitude and slowly action. The HE staining illustrated the structural disorder of skeletal muscle.
     2. Rats bearing tumor grew slowly because of tumor. Their weight were lower than normal group 7 days after modeling(P<0.05); Xiaotan Sanjie Decoction group's was higher than that of no-drugs group (P<0.05) but was lower than normal group 21 days after modeling (P<0.05)
     3. Total protein and albumin exam showed:compared with normal group, total protein of no-drugs group and Xiaotan Sanjie Decoction group were not lower (P>0.05). Albumin of all rats bearing tumor was decreased (P<0.05). Albumin of Xiaotan Sanjie Decoction group's was higher than that of no-drugs group (P<0.05).
     4. The results of Xiaotan Sanjie Decoction affecting the expressions of serum TNF-a protein showed:the expressions of serum TNF-a protein of rats bearing tumor were higher than those of normal rats (P<0.05). Xiaotan Sanjie Decoction group was lower than no-drugs group (P<0.05)
     The results of Xiaotan Sanjie Decoction affecting the expressions of serum IL-6 protein showed:the expressions of serum IL-6 protein of rats bearing tumor were higher than those of normal rats (P<0.05). Xiaotan Sanjie Decoction group was lower than no-drugs group (P<0.05)
     5. The results of Xiaotan Sanjie Decoction affecting the expressions of TNF-a protein in muscle tissues showed:the expressions of TNF-a protein in muscle tissues of rats bearing tumor were higher than those of normal rats (P<0.05). Xiaotan Sanjie Decoction group had no difference with no-drugs group (P>0.05)
     The results of Xiaotan Sanjie Decoction affecting the expressions of TNF-a mRNA in muscle tissues showed:the expressions of TNF-amRNA in muscle tissues of rats bearing tumor were higher than those of normal rats (P<0.05). Xiaotan Sanjie Decoction group had no difference with no-drugs group (P>0.05)
     The results of Xiaotan Sanjie Decoction affecting the expressions of TNF-a protein in livers showed:the expressions of TNF-a protein of rats bearing tumor were higher than those of normal rats (P<0.05). Xiaotan Sanjie Decoction group was lower than no-drugs group (P<0.05)
     6. The results of Xiaotan Sanjie Decoction affecting the expressions of IL-6 protein in muscle tissues showed:the expressions of IL-6 protein in muscle tissues of rats bearing tumor were higher than those of normal rats (P<0.05). Xiaotan Sanjie Decoction group had no difference with no-drugs group (P>0.05).
     The results of Xiaotan Sanjie Decoction affecting the expressions of IL-6 mRNA in muscle tissues showed:the expressions of IL-6 mRNA in muscle tissues of rats bearing tumor were higher than those of normal rats (P<0.05). Xiaotan Sanjie Decoction group had no difference with no-drugs group (P>0.05)
     The results of Xiaotan Sanjie Decoction affecting the expressions of IL-6 protein in livers showed:the expressions of IL-6 protein of rats bearing tumor were higher than those of normal rats (P<0.05). Xiaotan Sanjie Decoction group was lower than no-drugs group (P<0.05)
     7. The results of Xiaotan Sanjie Decoction affecting the expressions of NF-Kb protein in muscle tissues showed:the expressions of NF-Kb protein in muscle tissues of rats bearing tumor were higher than those of normal rats (P<0.05). Xiaotan Sanjie Decoction group had no difference with no-drugs group (P>0.05)
     The results of Xiaotan Sanjie Decoction affecting the expressions of NF-Kb mRNA in muscle tissues showed:the expressions of NF-κb mRNA in muscle tissues of rats bearing tumor were higher than those normal rats (P<0.05). Xiaotan Sanjie Decoction group had no difference with no-drugs group (P>0.05)
     8. The results of Xiaotan Sanjie Decoction affecting the expressions of Ubiquitin protein in muscle tissues showed:the expressions of Ubiquitin protein in muscle tissues of rats bearing tumor were higher than those normal rats (P<0.05). Xiaotan Sanjie Decoction group was lower than no-drugs group (P<0.05)
     The results of Xiaotan Sanjie Decoction affecting the expressions of Ubiquitin mRNA in muscle tissues showed:the expressions of Ubiquitin mRNA in muscle tissues of rats bearing tumor were higher than those normal rats (P<0.05). Xiaotan Sanjie Decoction group was lower than no-drugs group (P<0.05)
     Conclusion
     1. The subcutaneous model of Carcinosarcome Walker 256 in rats, which is made simply and has a high successful rate, is similar to the biological features of tumor protein metabolic abnormalities.
     2. Xiaotan Sanjie Decoction can conspicuously inhibit the weight lost of tumor-bearing rats.and Improve the level of serum albumin of tumor-bearing rats.
     3. They are confirmed that inflammation is correlated to tumor protein metabolic abnormalities, phlegm pollution hypothesis about tumor metabolic abnormalities is scientific and muddy phlegm exists corporeally, because the expressions of inflammatory factors increasing in serum, liver and muscle tissues.
     4. Xiaotan Sanjie Decoction can down-regulate the expressions of TNF-a and IL-6 in liver of tumor-bearing rats, regulation of liver protein synthesis. Down-regulate the expressions of ubiquitin in muscle tissues of tumor-bearing rats, and regulat skeletal muscle ATP-ubiquitin-proteasome. This may be one of the mechanisms of Xiaotan Sanjie Decoction adjusting tumor metabolic abnormalities and clearing phlegm polluted environment.
引文
[1]Tisdale MJ. Tumor-host interactions. [J]. Cell Biochem 2004,93:871-877
    [2]Argil'es, J. M., Alvarez, B.,& L'opez-Soriano, F. J. The metabolic basis of cancer cachexia. [J]. Med Res Rev 1997,17:477-498
    [3]Harris RA, Joshi M, Jeoung NH. Mechanisms responsible for regulation of branched-chain amino acid catabolism. [J]. Biochem Biophys Res Commun 2004,313:391-396
    [4]魏品康,中药金龙蛇口服液临床应用报告,中医杂志,1996,37(增刊):421
    [5]李相勇,金龙蛇口服液治疗晚期胃癌的疗效观察,湖北中医杂志,2001,23(11):3-4
    [6]Argiles, J. M., Alvarez, B., Lopez-Soriano, F. J. The pivotal role of cytokines in muscle wasting during cancer. [J]. Inter. J. Biol.2005,37:2036-2046
    [7]K.B. Harvey, A. Bothe, G.L. Blackburn. Nutritional assessment and patient outcome during oncological therapy. [J]. Cancer 1979 43 (5):2065-2069
    [8]Inui A. Cancer anorexia-cachexia syndrome:current issuesin research and management. [J]. C.A. Cancer J.Clin.2002,52:72-91.
    [9]MacDonald N, Easson AM, Mazurak VC, et al. Understanding and managing cancer cachexia. [J].J Am. Coll. Surg.2003 197:143-61.
    [10]Argiles, J. M., Alvarez, B., Lopez-Soriano, F. J. Molecular mechanisms involved in muscle wasting in cancerand ageing:cachexia versus sarcopenia. [J]. Inter. J. Biol.2005 37: 1084-1104
    [11]Tisdale MJ. Biomedicine. Protein loss in cancer cachexia [J] Science,2000,289(5488):2293 —2294.
    [12]Guttridge DC, Mayo MW,Madrid LV,et al. NF-kappaB-induced loss of MyoD messenger RNA:possible role in muscle decay and cachexia [J]. Science,2000,289(5488):2363— 2366.
    [13]Newsholme EA, Parry-Billings M. Properties of glutamine release from muscle and importance for the immune system. [J]. Parenteral Enteral Nutr 1990,14:63-64.
    [14]Costelli, P.; Baccino, F. M. Mechanisms of skeletal muscle depletion in wasting syndromes: role of ATP-ubiquitin-dependent proteolysis. [J]. Curr. Opin. Clin. Nutr. Metab. Care 2003, 6:407-412;
    [15]Attaix D, Combaret L, Pouch M-N & Taillandier D Regulation of proteolysis. [J]. Curr Opin Clin Nutr Metab Care 2001,4:45-49;
    [16]Pickart CM Mechanisms underlying ubiquitination. [J].Annu Rev Biochem 2001,70: 503-533
    [17]Tisdale MJ Pathogenesis of cancer cachexia. [J]. Support Oncol 2003,1:159-168;
    [18]Argiles JM, Lopez-Soriano FJ The ubiquitin-dependent proteolytic pathway in skeletal muscle:its role in pathological states. [J]. Trends Pharmacol Sci 1996,17:223-226;
    [19]Wing SS, Haas AL, Goldberg AL Increase in ubiquitin-protein conjugates concomitant with the increase in proteolysis in rat skeletal muscle during starvation and atrophy denervation. [J]. Biochem J 1995,307:639-645;
    [20]Williams A, Sun X, Fischer JE et al The expression of genes in the ubiquitin-proteasome proteolytic pathway is increased in skeletal muscle from patients with cancer. [J]. Surgery 1999,126:744-749;
    [21]Smith KL, Tisdale MJ Increased protein degradation and decreased protein synthesis in skeletal muscle during cancer cachexia. [J]. Br J Cancer 1993,67:680-685
    [22]Nakashima, J., Tachibana, M., Ueno, M., Baba, S., and Tazaki, H. Tumor necrosis factor and coagulapathy in patient with prostate cancer. [J]. Cancer Res.1995,55:4881-4885
    [23]Oliff A, Defeo-Jones D, Boyer M, Martinez D, Kiefer D, Vuocolo G, Wolfe A, Socher SH. Tumors secreting human TNF/cachectin induce cachexia in mice. [J]. Cell 1987,50:555-563
    [24]Langstein HN, Doherty GM, Fraker DL, Buresh CM, Norton JA. The roles of gamma-interferon and tumor necrosis factor alpha in an experimental rat model of cancer cachexia. [J]. Cancer Res 1991,51:2302-2306.
    [25]N. Carbo, S. Busquets, M. Van Royen, B. Alvarez, F.J. Lopez-Soriano, J.M. Argiles, TNF-_ is involved in activating DNA fragmentation in skeletal muscle [J]. Br. J. Can.2002,86 (6): 1012-1016
    [26]Costelli P, Carbo N, Tessitore L, Bagby GJ, Lopez-Soriano FJ, Argiles JM, Baccino FM. Tumor necrosis factor-alpha mediates changes in tissue protein turnover in a rat cancer cachexia model. [J]. Clin Invest 1993,92:2783-2789.
    [27]Murray S, Schell K, McCarthy DO, Albertini MR. Tumor growth, weight loss and cytokines in SCID mice. [J]. Cancer Lett 1997,111:111-115.
    [28]Strassmann G, Fong M, Kenney JS, Jacob CO. Evidence for the involvement of interleukin 6 in experimental cancer cachexia. [J]. Clin Invest 1992,89:1681-1684
    [29]Strassmann G, Fong M, Freter CE, Windsor S, D'Alessandro F, Nordan RP. Suramin interferes with interleukin-6 receptor binding in vitro and inhibits colon-26-mediated experimental cancer cachexia in vivo. [J]. Clin Invest 1993,2:2152-2159.
    [30]Enomoto A, Rho MC, Fukami A, Hiraku O, Komiyama K, Hayashi M. Suppression of cancer cachexia by 20S,21-epoxy-resibufogenin-3-acetate-a novel nonpeptide IL-6 receptor antagonist. [J]. Biochem Biophys Res Commun 2004,323:1096-1102.
    [31]Barton BE, Cullison J, Jackson J, Murphy T. A model that reproduces syndromes associated with human multiple myeloma in nonirradiated SCID mice. [J]. Proc Soc Exp Biol Med 2000,223:190-197.
    [32]Barton BE and Murphy TF. Cancer cachexia is mediated in part by the induction of IL-6-like cytokines from the spleen. Cytokine 2001,16:251-257.
    [33]Negri DR, Mezzanzanica D, Sacco S, Gadina M, Benigni F, Cajola L, et al. Role of cytokines in cancer cachexia in a murine model of intracerebral injection of human tumours. [J]. Cytokine 2001,15:27-38.
    [34]Zaki MH, Nemeth JA, Trikha M. CNTO 328, a monoclonal antibody to IL-6, inhibits human tumor-induced cachexia in nude mice. [J]. Int J Cancer 2004,111:592-595.
    [35]Lorite MJ, Thompson MG, Drake JL, Carling G, Tisdale MJ. Mechanism of muscle protein degradation induced by a cancer cachectic factor. [J]. Br J Cancer 1998,78:850-856.
    [36]Smith HJ, Lorite MJ, Tisdale MJ. Effects of a cancer cachectic factor on protein synthesis/degradation in murine C2C12 myoblasts:modulation by eicosapentaenoic acid. [J]. Cancer Res 1999,59:5507-5513.
    [37]Smith HJ, Wyke SM, Tisdale MJ. Role of protein kinase C and NF-kappaB in proteolysis-inducing factor-induced proteasome expression in C(2)C(12) myotubes. [J]. Br J Cancer 2004,90:1850-1857
    [38]Fearon, K. C., Falconer, J. S., Slater, C., McMillan, D. C., Ross, J. A.,& Preston, T. Albumin synthesis rates are not decreased in hypoalbuminemic cachectic cancer patients with an ongoing acute-phase protein response. [J].Ann. Surg.,1998,227:249-254
    [39]Falconer, J. S., Fearon, K. C. H., Plester, C. E., Ross, J. A.,& Carter D. C. (1994). Cytokines, the acute-phase response, and resting energy expenditure in cachectic patients with pancreatic cancer [J]. Ann. Surg.1994,219:325-331
    [40]Moshage, H. Cytokines and the hepatic acute phase response [J]. Pathol.1997,181:257-266
    [41]Smith HJ, Mukerji P, Tisdale MJ. Attenuation of proteasome-induced proteolysis in skeletal muscle by b-hydroxy-b-methylbutyrate in cancer-induced muscle loss. [J]. Cancer Res. 2005,65:277-83.
    [42]Nishihira T, Takagi T, Kawarabayashi Y, Izumi U, Ohkuma S, Koike N, Toyoda T, Mori S. Anti-cancer therapy with valine-depleted amino acid imbalance solution. [J]. Tohoku J Exp Med.1988,156:259-270.
    [43]Ishiwata K, Kubota K, Murakami M, Kubota R, Senda M. A comparative study on protein incorporation of L-[methyl-3H]methionine, L-[1-14C] leucine and L-2-[18F] fluorotyrosine in tumor bearing mice. [J]. Nucl Med Biol.1993,20:895-899.
    [44]Paxton K, Ward LC, Wilce PA. Amino acid oxidation in the tumor-bearing rat. [J]. Cancer Biochem Biophys.1988,9:343-351.
    [45]Le Bricon T, Cynober L, Field CJ, Baracos VE. Supplemental nutrition with ornithine a-ketoglutarate in rats with cancer-associated cachexia:surgical treatment of the tumor improves efficacy of nutritional support. [J]. J Nutr.1995,125:2999-3010.
    [46]Kawamura I, Sato H, Ogoshi S, Blackburn GL. Use of an intravenous branched chain amino acid enriched diet in the tumor-bearing rat. [J]. Jpn J Surg.1985,15:471-476.
    [47]Argiles JM, Lopez-Soriano FJ. The oxidation of leucine in tumour-bearing rats. [J]. Biochem J.1990,268:241-244.
    [48]Siddiqui RA, Williams JF. The regulation of fatty acid and branched-chain amino acid oxidation in cancer cachectic rats:a proposed role for a cytokine, eicosanoid, and hormone trilogy. [J]. Biochem Med Metab Biol.1989,42:71-86
    [49]Goodlad GAJ, Tee MK, Clark CM. Leucine oxidation and protein degradation in extensor digitorum longus and soleus of the tumor-bearing host. [J]. Biochem Med.1981,26:143-147
    [50]Argiles JM, Lopez-Soriano FJ. Oxidation of branched-chain amino acids in tumor-bearing rats. Biochem Soc Trans. [J].1989,17:1044-1045.
    [51]Gomes-Marcondes MC, Ventrucci G, Toledo MT, Cury L, Cooper JC. A leucine-supplemented diet improved protein content of skeletal muscle in young tumor-bearing rats. [J]. Braz J Med Biol Res.2003,36:1589-1594.
    [52]Ventrucci G, Mello MA, Gomes-Marcondes MC. Effect of a leucinesupplemented diet on body composition changes in pregnant rats bearing Walker 256 tumor. [J]. Braz J Med Biol Res.2001,34:333-338.
    [53]Ventrucci G, de Mello MA, Gomes-Marcondes MC. Effects of leucine supplemented diet on intestinal absorption in tumor bearing pregnant rats. [J]. BMC Cancer.2002,2:7.
    [54]Ventrucci G, Mello MA, Gomes-Marcondes MC. Proteasome activity is altered in skeletal muscle tissue of tumour-bearing rats fed a leucine-rich diet. [J]. Endocr Relat Cancer.2004, 11:887-895.
    [55]Costelli P, Llovera M, Garcia-Martinez C, Carbo N, Lopez-Soriano FJ, Argiles JM. Enhanced leucine oxidation in rats bearing an ascites hepatoma (Yoshida AH-130) and its reversal by clenbuterol. [J]. Cancer Lett.1995,91:73-78.
    [56]Busquets S, Alvarez B, Lopez-Soriano FJ, Argiles JM. Branched-chain amino acids:a role in skeletal muscle proteolysis in catabolic states? [J]. J Cell Physiol.2002,191:283-289.
    [57]Komatsu H, Nishihira T, Chin M, Doi H, Shineha R, Mori S, Satomi S. Effect of valine-depleted total parenteral nutrition on fatty liver development in tumor-bearing rats.[J]. Nutrition.1998,14:276-281.
    [58]Crosby LE, Bistrian BR, Ling P, Istfan NW, Blackburn GL, Hoffman SB. Effects of branched chain amino acid-enriched total parenteral nutrition on amino acid utilization in rats bearing Yoshida sarcoma. [J]. Cancer Res.1988,48:2698-2702.
    1、K.B. Harvey, A. Bothe, G.L. Blackburn. Nutritional assessment and patient outcome during oncological therapy. [J]. Cancer 1979 43 (5):2065-2069
    2、Inui A. Cancer anorexia-cachexia syndrome:current issuesin research and management. [J]. CA. Cancer J. Clin.200252:72-91.
    3、MacDonald N, Easson AM, Mazurak VC, et al. Understanding and managing cancer cachexia. [J].J Am. Coll. Surg.2003197:143-61.
    4、Argiles, J. M., Alvarez, B., Lopez-Soriano, F. J. The pivotal role of cytokines in muscle wasting during cancer.[J]. Inter. J. Biol.200537:2036-2046
    5、Argiles, J. M., Alvarez, B., Lopez-Soriano, F. J. Molecular mechanisms involved in muscle wasting in cancerand ageing:cachexia versus sarcopenia. [J]. Inter. J. Biol.200537:1084-1104
    6、S.Warren, The immediate cause of death in cancer, Am. [J]. J.Med. Sci.1932,184:610-613
    7、Argiles, J. M., Alvarez, B., Lopez-Soriano, F. J. The metabolic basis of cancer cachexia. [J]. Med. Res. Rev.,1997 17:477-198
    8、崔慧娟,李佩文,李园等肺癌恶病质的中医辨证分型[J].内蒙古中医药,2002,21(5):1—2
    9、申维玺,刘玉梅细胞因子网络与中药的作用机理[J].世界科学技术-中药现代化基础研究,2000,2(6):24—27
    10、申维玺,孙燕,张叔人等白细胞介素1等细胞因子与肺阴虚证的研究[J].中医杂志,2000,41(7):423—425
    11、申维玺,孙燕细胞因子网络紊乱是疾病的基本发病学机理[J].医学研究通讯,2000,29(7):124—126
    12、韩美君,宫晓虹,王善利等TNF—α与中医阴虚证相关性的研究[J].大连大学学报,2005, 26(4):76—78
    13、姜军康莱特注射液治疗晚期癌症恶病质37例临床观察[J].青海医药杂志,2001,31(9):16
    14、刘爱国康莱特对晚期癌症患者血清恶病质细胞因子的影响[J].中国肿瘤临床康莱特专辑,2002.4:18
    15、赵忠仁康莱特联合放疗治疗中晚期恶性肿瘤的临床研究[J].现代肿瘤医学,2005,13(1):17—72
    16、周毅,何捷,刘旭荣康莱特注射液配合胃肠外营养治疗癌症恶液质[J].中国肿瘤,2006,15(9):635-636
    17、蔡洪培,谢渭芬,陈岳祥等三氧化二砷对腹腔荷瘤裸鼠的抗恶病质效应[J].第二军医大学学报,2002,23(3):279—280
    18、贾勇士,吴树强,钦志泉鸦胆子油乳配合介入治疗原发性肝癌的临床分析[J].中国中药杂志,2003(3):683—684
    19、许尤琪薛惠宁邹军复方苦参注射液联合化疗治疗恶性肿瘤近期疗效和毒副作用观察[J].安徽中医临床杂志,2001,13(3)160—162
    20、刘俊保,姚志伟白花蛇舌草注射液对原发性肝癌的临床作用[J].医药论坛杂志,2004,25(15):37—38
    21、黄挺,陈震,李 勇参麦液抗肿瘤作用及其对糖代谢的影响[J].中成药,2003,25(5):390—393
    22、葛成华,范成美,王世伟等生脉注射液在胃癌根治术后化疗中的作用[J].药学服务与研究,2005,5(3):292—295
    23、崔慧娟李园万冬桂等参附注射液抗癌症恶病质的临床研究[J].中国肿瘤临床与康复,2005,12(5):478—480
    24、杨宇飞,吴煜,邬冬华参附注射液抗癌症恶病质基因芯片研究[J].中国实验方剂杂志,2001,10(2):22—25
    25、刘昳,叶峰,邱根全等白术内酯1对肿瘤恶病质患者细胞因子和肿瘤代谢因子的影响[J].第一军医大学学报,2005,25(10):1308—1311
    26、武珊珊,高文远,段宏泉等重楼化学成分和药理作用研究进展[J].中草药,2004,35(3):344—347
    27、徐术,胡晋红,全山丛 白芷的活性成分研究与临床应用进展[J].中国药房,2005,16(6):467—469
    28、张静中药对癌症患者恶病质状态的影响[J].中国中西医结合杂志,2000,20(11):871
    29、蔡红兵,罗荣城,杨传标等补中益气汤治疗癌症食欲不振—恶病质综合征30例疗效观察[J].新中医,2003,35(3):25—26
    30、王守峰,张峰中医辨证配合小剂量化疗治疗晚期原发性肝癌疗效观察[J].内蒙古中医药,2000,19(4):2—3
    31、耿东升十全大补汤研究进展[J].中成药,2003,25(10):837—840
    32、许玲、陈亚琳、刘咏英等金龙蛇口服液合华蟾素注射液、黄芪注射液治疗Ⅳ期胃癌的临床观察[J].成都中医药大学学报,2005,28(1):7—9
    33、李相勇、魏品康金龙蛇口服液治疗晚期胃癌的疗效观察[J].湖北中医杂志,2001,23(11):3—5
    34、孙彤,王曙光,吴飞雪复方守宫散治疗肿瘤恶病质的临床研究[J].安徽中医学院学报,2003,22(6):19-20

© 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