臭氧自体血回输治疗对脂肪性肝病血清细胞因子的影响
摘要
目的：观察高压臭氧自体血回输治疗对脂肪性肝病患者血清瘦素、白介素-6、高敏C反应蛋白、一氧化氮、氧化低密度脂蛋白、8异前列腺素F2a水平的影响,探讨臭氧自体血回输治疗对脂肪性肝病及其并发症的潜在预防及治疗作用。方法：选取2009年10月至2010年6月于新疆医科大学附属第一医院肝病科住院治疗的脂肪性肝病患者40例(按排除标准剔除4例),依照患者治疗意愿分为臭氧自体血回输治疗组(治疗组)和对照组,所有伴有糖尿病及血脂紊乱的入选者均接受专业的降糖和／或降脂治疗,所有入选者基础治疗相同,在此基础上治疗组接受臭氧自体血回输治疗,对照组不接受任何抗氧化治疗。治疗前测定全部入选者血清瘦素、白介素-6、高敏C反应蛋白、一氧化氮、氧化低密度脂蛋白、8异前列腺素F2a水平,于治疗疗程结束后再次测定上述血清细胞因子指标进行比较。结果：两组患者在年龄,民族,性别,体重指数,伴有的2型糖尿病及血脂紊乱基线情况具有良好的均衡可比性,治疗前脂肪性肝病患者血清白介素-6、高敏C反应蛋白、一氧化氮、氧化低密度脂蛋白水平差异无统计学意义,治疗组血清瘦素水平明显高于对照组(P=0.03),而8异前列腺素F2a水平明显低于对照组(P=0.00),差异具有统计学意义；治疗疗程结束后比较两组患者血清瘦素、高敏C反应蛋白、白细胞介素-6、一氧化氮、氧化低密度脂蛋白治疗前后差值,差异无统计学意义,血清8异前列腺素F2a治疗前后差值仍具有统计学意义,但差异性降低(治疗前P=0.00,治疗后P=0.02)。结论：臭氧自体血回输治疗可降低脂肪性肝病患者血清瘦素水平,改善瘦素抵抗,对脂肪性肝病及其远期预后可能有预防及治疗作用。
Objective:The aim of this study was to assess the effect of ozone treatment on leptin, interleukin-6 (I-6L), high sensitivity C-reactive protein (hs-crp), NO, oxidized low-density lipoprotein (oxLDL),8-iso-prostaglandin F2a (8iso-PGF2a) levels in patients with non-alcoholic fatty liver disease (NAFLD). Methods:The study conducted at the Hepatology Department of First Affiliated Hospital of Xinjiang Medical University.Thirty-six FLD patients were selected, who were not undergoing any antioxidant treatment were divided into treatment and control groups. The treatment group comprised patients who willingly received ozone-enriched autologous blood transfusion (OATT). Patients with type 2 diabetes mellitus (T2DM) or dyslipidemia received professional guidance for lowering of blood lipids and sugar treatment. Patients in the treatment group received OATT, while the patients in the control group did not receive any antioxidant treatment. Results:There were no significant intergroup differences with regard to the age, body mass index (BMI), ethnicity, sex, T2DM, and dyslipidemia. The baseline serum leptin (P= 0.03) levels were significantly higher and 8iso-PGF2a (P= 0.00) levels significantly lower in the treatment group than those in the control group. No significant intergroup difference was observed in the serum leptin levels at the end of the study period. Conclusion:Ozone intervention decreased serum leptin levels of FLD patients in only 5 weeks. However, further clinical studies need to be performed to identify the potential for the use of ozone as an antioxidant in patients with FLD, and the mechanism(s) that improve leptin resistance in patients who receive ozone.
Objective:The aim of this study was to assess the effect of ozone treatment on leptin, interleukin-6 (I-6L), high sensitivity C-reactive protein (hs-crp), NO, oxidized low-density lipoprotein (oxLDL),8-iso-prostaglandin F2a (8iso-PGF2a) levels in patients with non-alcoholic fatty liver disease (NAFLD). Methods:The study conducted at the Hepatology Department of First Affiliated Hospital of Xinjiang Medical University.Thirty-six FLD patients were selected, who were not undergoing any antioxidant treatment were divided into treatment and control groups. The treatment group comprised patients who willingly received ozone-enriched autologous blood transfusion (OATT). Patients with type 2 diabetes mellitus (T2DM) or dyslipidemia received professional guidance for lowering of blood lipids and sugar treatment. Patients in the treatment group received OATT, while the patients in the control group did not receive any antioxidant treatment. Results:There were no significant intergroup differences with regard to the age, body mass index (BMI), ethnicity, sex, T2DM, and dyslipidemia. The baseline serum leptin (P= 0.03) levels were significantly higher and 8iso-PGF2a (P= 0.00) levels significantly lower in the treatment group than those in the control group. No significant intergroup difference was observed in the serum leptin levels at the end of the study period. Conclusion:Ozone intervention decreased serum leptin levels of FLD patients in only 5 weeks. However, further clinical studies need to be performed to identify the potential for the use of ozone as an antioxidant in patients with FLD, and the mechanism(s) that improve leptin resistance in patients who receive ozone.
引文
[1]范建高,曾民德.脂肪性肝病[M].北京：人民卫生出版社,2005,306～321.
[2]范建高,蔡晓波.非酒精性脂肪性肝病促进动脉粥样硬化的发生[J].中国动脉硬化杂志,2008,16(1)：1～3.
[3]范建高.非酒精性脂肪肝与代谢综合征[J].国外医学内分泌学分册,2002,22(5)：273～275.
[4]Clark JM, Diehl AM. Defining nonalcoholic fatty liver disease:implication for epidemiologic studies [J]. Gastroenterogy,2003,124(1):248～250.
[5]马晓燕.益气化痰消癖法治疗脂肪肝临床研究[J].山西中医药研究,2000,3(16)：32.
[6]范建高.酒精性与非酒精性脂肪性肝病[J].中华肝脏病杂志,2003,11(11)：692.
[7]卢晓岚,陶明,罗燕,等.饮酒与肝病流行病学调查[J].中华肝脏病杂志,2002,10(6)：467～468.
[8]曾民德脂肪肝发病机制”二次打击”假设[J].肝脏,2001,6(3)：14.
[9]Day CP, James OF. Steatohepatitis:a tale of two "hits" [J]? Gastroenterology,1998, 114(4):842～845.
[10]季光,张莉.重视非酒精性脂肪性肝病胰岛素抵抗的防治[J].世界华人消化杂志,2010,18(4)：1469～1473.
[11]Angulo P. Nonalcoholic fatty liver disease [J]. N Eng J Med,2002,346(16): 1221-1231.
[12]Medina Fernandez-Salazar LI, Garcia-Buey Moreno-Otero R. Approach to the pathogenesis and treatment of nonalcoholic steatohepatitis [J]. Diabetes Care,2004, 27(8):2057～2066.
[13]Rodriguez G, Gallego S, Breidenassel C, et al. Is liver transaminases assessment an appropriate tool for the screening of non-alcoholic fatty liver diseases in at risk obese children and adolescents [J]? Nutr Hosp,2010,25(5):712～717.
[14]Younossi ZM, Diehl AM, Ong JP. Nonalcoholic fatty liver disease:an agenda for clinical research [J]. Hepatology,2002; 35(4):746～752.
[15]Sanyal AJ. AGA technical review on nonalcoholic fatty liver disease [J]. Gastroenterology,2002,125(3):1705～1725.
[16]周卫东,杨亚玲,车志宏,等.非酒精性脂肪肝与超敏C反应蛋白、胰岛素抵抗的关系[J].中南大学学报：医学版,2008,33(7)：565～570.
[17]Yoneda M, Mawatar I H, Fujita K, et al. Highsensitivity C-reactive protein is an independent clinical feature of nonalcoholic steatohepatitis (NASH) and al-so of the severity of fibrosis in NASH [J]. J Gastroenterol,2007,42 (7):573-582.
[18]Poordad FF. The role of leptin in NAFLD:contender or pretender [J]? J Clin Gastroenterology,2004,38(10):841～63.
[19]Angulo P, Alba LM, Petro Vic LM. Leptin, insulin resistance, and liver fibrosis in human nonalcoholic fatty liver disease [J]. J Hepatol,2004,41(6):943～949.
[20]Alwayn IP, Andersson C, Lee S, et al. Inhibition of matrix metalloproteinases increases PPAR-alpha and IL-6 and p revents dietary-induced hepatic steatosis and injury in a murine model [J]. Am J Physiology Gastrointestinal Liver Physiology, 2006,291(6):1011-1009.
[21]Eiserich J P, Patel R P, Odonnel V B. Pathophysiology of nitric oxide and related species; free radical reactions and modification of biomolecules[J]. Mol Aspects Med, 1998,19(4-5):221～357.
[22]周荣根.脂肪肝与OX-LDL异常的中医分型治疗[J].云南中医中药杂志,2005,26(6)：64～65.
[23]Zimran A, Wasser G, Forman L, et al. Effect of ozone on red blood cell enzymes and intermediates [J]. Acta Haematol,2000,102 (3):148～151.
[24]Larini A, Bianchi L, Bocci V. The ozone tolerance:Enhancement of antioxidant enzymes is ozone dose dependent in Jurkat cells [J]. Free Radic Res,2003,37 (11): 1163-1168.
[25]Zamora ZB, Borrego A, Lopez OY, et al. Effects of ozone oxidative preconditioning on TNF-alpha release and antioxidant prooxidant intracellular balance in mice during endot oxic shock [J]. Mediators Inflamm,2005,2005 (1):16～22.
[26]郭亚兵.医用臭氧在内科临床中的应用[J].中华实验和临床感染病杂志(电子版),2008,2(1)：106.
[27]中华医学会肝脏病学会脂肪肝和酒精性肝病学组.非酒精性脂肪性肝病诊疗指南[J].肝脏,2006,11(11)：68～70.
[28]陈言东,党彤,孟宪梅.脂肪肝患者血清瘦素水平研究[J].包头医学院学报,2010,26(1)：42～44.
[29]Bugianesi E. Leone N, Vanni E, et al. Expanding t he natural history of nonalcoholic steatohepatitis:from cryptogenic cirrhosis to hepatocellular carcinoma [J]. Gast roenterology,2002,123 (1):134～140.
[30]E.Bugianesi MD. nonalcoholic Steatohepatitis and cancer [J]. Clinics in Liver Desease,2007,11(1):191～207.
[31]胡中伟,郭家伟,邓西龙.非酒精性脂肪肝与血清瘦素和胰岛素抵抗关系[J].南方医科大学学报,2006；26(6)：853～855.
[32]Sanyal AJ, Campbell-Sargent C, Mishahi F, et al. Non-alcoholic steatohepatitis: Association of insulin resistance and mitochondrial abnoemalities [J]. Gastroenterology,2001,120 (5):1183～1193.
[33]Gornicki A, Gutsze A. In vitro effects of ozone on human erythrocyte emembranes: an EPR study [J]. Acta Biochim Pol,2000,47 (4):963-971.
[34]Tsukamoto H, Rippe R, Niemela O. Roles of oxidative stress in activation of Kupffer and Ito cells in liver fibro genesis [J]. J Gast rent-roll Hepatol,1995; 10 (Supple l):S50-52.
[35]乔汗晨.非酒精性脂肪肝病研究进展[J].新乡医学院学报,2006,23(6)：630～634.
[36]Lieber CS. New concepts of the alcoholic liver disease lead to noveltreatments [J]. Cuur Gast roenterol Rep,2004,6:60～65.
[37]韩萍,成军,李莉.非酒精性脂肪肝炎的研究[J].世界华人消化杂志,2002,10(9)：1038～1039.
[38]成军,李莉,张玲霞,陈菊梅.丙型肝炎病毒感染与脂类代谢的相关性[J].肝脏2002；7：56～58.
[39]Weltman MO, Farrell GC, Liddle C. Increased hepatocyteCYP2El expression in a rat nutritional model of hepatic steatosis with inflammation [J]. Gastroenterology 1996; 111:1645～1650.
[40]吴勤,成军,李莉.酒精性脂肪肝的研究[J].世界华人消化杂志,2002,10(9)：1037～1038.
[41]Choudhury J, Sanyal AJ. Insulin resistance and the pathogenesis of nonalcoholic fatty liver disease [J]. Clin liver Dis,2004,8(3):575～594.
[42]Saxena N K, Ikeda K, Rockeyd C, et al. Leptin in hepatic fibrosis:evidence for increased collagen Production in stellate cells and lean littermates of obPob mice [J]. Hepatol,2002,35(4):762～771.
[43]Wang MY, Zhou YT, Newgard CB, et al. A novel leptin receptor isoform in rat [J]. F EBS Lett,1996,392(2):87～90.
[44]CHITTURI S, ABEYGUNADEKERA S, FARRELL GC, et al. NASH and insulin resistance:Insulin hypersecretion and specific association with the insulin resistance syndrome [J]. Hepatol,2002,35(2):497～499.
[45]Barek J, Bartos J, Galuska J, et al. Expression of ob-gene coding the production of the hormone leptin in hepatocytes of liver with steatosis [J]. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub,2001,145 (1):15-20.
[46]马向华,王维敏.非酒精性脂肪肝患者瘦素抵抗和胰岛素抵抗研究[J].中华肝脏病杂志,2004,12(11)：651～655.
[47]Bethanis SK, Theohari's SE. Leptin in the Field of Hepatic FIbrosis:A Pivotal or an Incidental Player [J]? Dig Dis Sci 2006,51(10):1685-1696.
[48]Lydatakis H, Hager IP, Kostadelou E,et al. Noninvasive markers to predict the liver fibrosis in non-alcoholic fatty liver disease [J]. Liver Int,2006,26(7):864～871.
[49]Namecz M, Preiniger K, Englishch R, et al. Acute effect of leptin on hepatic glycogenolysis and gluconeogenesis in perfused rat liver [J]. Hepatology,1999,29 (1); 166～172.
[50]Dong H, Lu FE, Gao ZQ, et al. Effect s of emodin ont reating murine nonalcoholic fatty liver induced by high caloric laboratory chaw [J]. World J Gast roenterol,2005, 11 (9):1339～1344.
[51]农兵,罗和生.瘦素在实验性大鼠肝纤维化发生中的作用机制初探[J].内科,2007,2(1)：7～11.
[52]Ibabe A, Bilbao E, Cajaraville MP, et al. Expression of peroxisome proliferator Oactivated receptors in zebrafish (Danio rerio) depending on gender and developmental stage [J]. Histochem Cell Biol,2005,123 (1):75-87.
[53]杨辉,李瑜元,江庆澜,等.瘦素与非酒精性脂肪肝的关系[J].广州医学院学报,2005,33(5)：10～13.
[54]Chitturi S, Farrell GC, Hashimoto E, et al. Non-alcoholic fatty liver disease in the Asia-Pacific region:definitions and overview of proposed guidelines [J]. J Gastroenterol Hepatol,2007,22(6):778-87.
[55]Chitturi S, Farrell GC. Etiopathogenesis of nonalcoholic steatohepatitis [J]. Semin Liver Dis,2001; 21(1):27-41.
[56]丁佳,范竹萍.非酒精性脂肪肝和心血管疾病[J].国际消化病杂志,2008,28(4)：320～322.
[57]Bugianesi E, Manzini P, D'Antico S, et al. Relative contribution of iron burden, HFE mutations, and insulin resistance to fibrosis in nonalcoholic fatty liver[J]. Hepatology, 2004; 39(6):179～187.
[58]卫建筠,杨海红,曾文铤.非酒精性脂肪肝患者血清瘦素水平与肝纤维化关系研究[J].临床医学工程,2009,16(4)：46～47.
[59]Cortez-Pinto H, Camilo ME, Baptista A, et al. Non-alcoholic fatty liver, Another feature of the metabolic syndrome [J]. Clin Nut r,1999,18(6):353～358.
[60]Chen X, Osborne M C, Rybczynski P J, et al. Pharmacological profile of a novel, non-OTZD PPAR-gamma agonist [J]. Diabetes Obes Metab,2005,7(5):536～546.
[61]黄伟,季峰,姜玲玲,等.脂肪肝患者血清瘦素水平检测及其与发病的关系[J].中华检验医学杂志,2004,27(2)：106.
[62]Marsh DJ, Hollopeter G, Huszar D, et al. Response of neuropeptide Y deficient mice to feeding effectors [J]. Nat Genet,1998,25(75-76):119～122.
[63]Cohen B, Novick D, Rubinstein M. Modulation of insulin activity by leptin [J]. Science,1996,274 (5290):1185～1188.
[64]Laubner K, Kieffer T J, Lam N T, et al. Inhibition of prepro-insulin gene expression by leptin induction of suppressor of cytokine signaling 3 in pancreatic beta-cells [J]. Diabetes,2005,54:3410-3417.
[65]Considine RV, Sinha MK, Heiman ML, et al. Serum immunoreactive-leptin concentrations in normal-weight and obesehumans [J]. N Eng JMed,1996,334(5): 292～296.
[66]魏良洲,杨正武.瘦素、胰岛素在非酒精性脂肪肝发病中的作用[J].临床肝胆病杂志,2006,22(1)：71～73.
[67]Beckman JS, KoppenolWH. Nitric oxide, superoxide, and peroxynitrite:the good, the bad, and ugly [J]. Am J Physi2ol,1996; 271 (5):C1424-1437.
[68]Ekstedt M, Franzen LE, Mathiesen UL. Long term followup of patients with NAFLD and elevated liver enzymes [J]. Hepatology,2006,44:865～873.
[69]Raij L. Nitric oxide in the pathogenesis of cardiac disease [J]. Clin Hypertens (Greenwich),2006; 8 (12 Supp 1):S30-39.
[70]Cengel A, Sahinarslan A. Nitric oxide and cardiovascular system [J]. Anadolu Kardiyol Derg,2006; 6 (4):364～368.
[71]王秀红,路方红.内皮素、一氧化氮与心血管疾病[J].中国慢性病预防与控制,2005,13(3)：139～141.
[72]Beckman JS, KoppenolWH. Nitric oxide, superoxide, and peroxynitrite:the good, the bad, and ugly [J]. Am J Physi2ol,1996; 271(5):C1424～1437.
[73]吕天英,卢震亚.非酒精性脂肪性肝病大鼠肝组织NO和iNOS的变化[J].浙江预防医学,2009,21(4)：9～11.
[74]Sanchez-M, argalet V, Martin-Romero C.Human leptin signaling in human peripheral blood mononuclear cells:Activation of the JAK-STAT pathway [J].Cell Immuno, 2001, (211):30-36.
[75]Yin XY, Jiang JM, Liu JY, et al. Effects of endogenous nitric oxide induced by 5-fluorouracil and L-Arg on liver carcinoma in nude mice [J]. World J Gastroenterol, 2007,13 (46):6249～6253.
[76]温继梨,承喜凤,陈凤英.一氧化氮与心血管疾病[J].内蒙古医学院学报,2008,30(3)：223～228.
[77]Pratico D, Lawson JA, Rokach J, et al. The isoprostanes in biology and medicine. Trends Endocrinol Metab,2001,12(6):243～7.
[78]Janssen LJ. Isoprostanes:an overview and putative roles in pulmonary pathophysiology. Am J Physiol Lung Cell Mol Physiol.2001,280(6):L1067-82.
[79]Rader D J. Effect of insulin resistance, dyslip idemia, and intraabdominal adiposity on the development of cardiovascular disease and diabetesmellitus [J]. Am J Med, 2007,120(3 Supp 11):S12-18.
[80]Feng R, HeW, Ochi H, et al. Ozone exposure impairs antigen specific immunity but activates IL-7 induced proliferation of CD4-CD8- thymocytes in BALB/c mice [J]. J Toxicol Environ Health A,2006,69 (16):1511-1526.
[81]Bocci V, Luzzi E, Corradeschi F, et al. Studies on the biological effects of ozone:5. Evaluation of immunological parameters and tolerability in normal volunteers receiving ambulatory autohaemotherapy [J]. Biotherapy,1993-1994,7 (2):83～90.
[82]Merin O, Attias E, Elstein D, et al. Ozone administration reduces reperfusion injury in an isolated rat heart model [J]. J Card Surg,2007,22 (4):339-342.
[83]Zamora ZB, Borrego A, Lopez OY, et al. Effects of ozone oxidative p reconditioning on TNF-alpha release and antioxidant prooxidant intracellular balance in mice during endo-toxic shock [J]. Mediators Inflamm,2005,2005 (1):16～22.
[84]Peralta C, Xaus C, Barttrons R, et al. Effect of ozone treatment on reactive oxygen species and adenosine production during hepatic is chemiareperfusion [J]. Free Radic Res,2000,33 (5):595～605.
[1]Day CP, James OF. Steatohepatitis:a tale of two "hits" [J]? Gastroenterology, 1998,114 (4):842～845.
[2]Choudhury J, Sanyal AJ. Insulin resistance and the pathogenesis of nonalcoholic fatty liver disease [J]. Clin liver Dis,2004,8(3):575～594.
[3]王征,刘东戈.非酒精性脂肪性肝炎与细胞因子[J].世界华人消化杂志,2007,15(3)：266～271.
[4]SAXENA N K, IKEDA K, ROCKEYD C, et al. Leptin in hepatic fibrosis:evidence for increased collagen Production in stellate cells and lean littermates of obPob mice [J]. Hepatol,2002,35(4):762-771.
[5]Wang MY, Zhou YT, Newgard CB, et al. A novel leptin receptor isoform in rat [J]. F EBS Lett,1996,392(2):87-90.
[6]CHITTURI S, ABEYGUNADEKERA S, FARRELL GC, et al. NASH and insulin resistance:Insulin hypersecretion and specific association with the insulin resistance syndrome [J]. Hepatol,2002,35(2):497-499.
[7]杨辉,李瑜元,聂玉强,等脂肪组织瘦素基因与非酒精性脂肪肝的研究[J].中华肝脏病杂志,2006,11(14)：828～831.
[8]HUAN J N, LI J, HAN Y, et al. Adipocyte selective reduction of the leptin receptors induced by antisense RNA leads to increased adiposity, dyslipidemia, and insulin resistance [J]. J Biol Chem,2003,278(46):45638-45650.
[9]马向华,王维敏.非酒精性脂肪肝患者瘦素抵抗和胰岛素抵抗研究[J].中华肝脏病杂志,2004,12(11)：651～655.
[10]Saxena NK, Ikeda K, Rockey DC, et al. Leptin in hepatic fibrosis:evidence for Increased collagen production in stellate cells and lean littermates of ob/ob mice [J]. Hepatology,2002,35 (4):762-771.
[11]Bethanis SK, Theohari's SE. Leptin in the Field of Hepatic Fibrosis:A Pivotal or an Incidental Player [J]? Dig Dis Sci 2006,51(10):1685-1696.
[12]Lydatakis H, Hager I P, Kostadelou E, et al. Noninvasive markers to predict the liver fibrosis in non-alcoholic fatty liver disease [J]. Liver Int,2006,26(7):864-871.
[13]Chitturi S, Farrell G, Frost L, et al. Serum leptin in NASH correlates with hepatic steatosis but not fibrosis:a manifestation of lipotoxicity [J]? Hepatology,2002,36(2): 403-409.
[14]杨辉,李瑜元,江庆澜,等.瘦素与非酒精性脂肪肝的关系[J].广州医学院学报,2005,33(5)：10～13.
[15]Scherer PE, Williams S, Fogliano M, et al. A novel serum protein similar to CIq, produced exclusively in adipocytes [J]. J Biol Chem,1995,270(45):26746-26749.
[16]Yamauchi T, Kamon J, Ito Y, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects [J]. Nature,2004,43(7021):762-769.
[17]Targher G, Bertolini L, Rodella S, et al. Associations between plasma adiponectin concentrations and liver histology in patients with nonalcoholic fatty liver disease [J]. Clin Endocrinol (Oxf),2006,64:679-683.
[18]Abiru S, Migita K, Maeda Y, et al. Serum cytokine and soluble cytokine receptor levels in patients with non-alcoholic steatohepatitis [J]. Liver Int,2006,26(1):39～45.
[19]Claudio P, Giorgio S, Walter E. Plasma adiponectin is decreased in nonalcoholic fatty liver disease [J]. Eur J Endocrinol,2004,152(1):113-118.
[20]Xu A,Wang Y, Keshaw H, et al. The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice [J]. Eur J Endoerinol, 2003,112(1):91-100.
[21]Vuppalanchi R, Marri S, Kolwankar D, et al. Is adiponectin involved in the pathogens is of nonalcoholic steatohepatitis? A preliminary human study [J]. J Clin Gastroenterology,2005,39(3):237-242.
[22]Yang H, Li YY, Nie YQ, Zhou YJ, DU YL, Sha WH, Hng Y. The relationship between insulin resistance and adiponectin gene expression in nonalcoholic fatty liver disease [J]. Zhonghua Ganzangbing Zazhi 2007; 15:525-528.
[23]Steppan CM, Baily ST, Bhat S, et al.The hormone resisistin links obesity to diabetes [J]. Nature,200,409(1):307-312.
[24]Steppan CM, Baily ST, Bhat S, et al. he hormone resisistin links obesity to diabetes [J].Regul Integr Comp Physiol,2005,288(5):1220-1225.
[25]Steppan CM, Bailey ST, Bhat S, et al. The hormone resistin links obesity to diabetes [J]. Nature,2001,49(18):307-312.
[26]杨文慧,赵和平.抵抗素与非酒精性脂肪性肝病[J].国际内科学杂志,2007,34(8)：452～455.
[27]Weisberg SP, McCann D, Desai M, et al. Obesity is associated with macrophage accumulation in adipose tissue [J]. J Clin Invest,2003,112(12):1796-1808.
[28]Smith SR, Bai F, Charbonneau C, et al. A promoter genotype and oxidative stress potentially link resistin to human insulin resistance [J]. Diabetes,2003,52(7): 1611-1618.
[29]STEPPAN C M, LAZAR M A. The current biology of resistin [J]. J Intern Med,2004, 255(4):439-447.
[30]Hartman HB, Hu X, Tyler KX, et al. Mechanisms regulating adipicyte expression of resistance [J]. J Biol Chem.2002,277(22):19754-19761.
[31]钱林,胡小宣.非酒精性脂肪肝分子发病机制的研究进展[J].世界华人消化杂志,2008,16(25)：2848～2852.
[32]王莹,蔡东联脂肪细胞因子与非酒精性脂肪肝相关性研究进展[J].国外医学卫生学分册,2008,35(5)：296-299.
[33]Haukeland JW, Damas JK, Konopski Z, et al. Systemic inflammation in nonalcoholic fatty liver disease is characterized by elevated levels of CCL2 [J]. J Hepatol 2006,44: 1167-1174.
[34]Wong VW, Hui AY, Tsang SW, et al. Metabolic and adipokine profile of Chinese patients with nonalcoholic fatty liver disease [J]. Clin Gastroenterol Hepatol,2006,4 (9):1154-1161.
[35]HOTAMISLIGIL G S, SHARGILL N S, SPIEGELMAN B M. Adipose expression of tumor necrosis factoralpha: direct role in obesity linked insulin resistance [J]. Sci, 1993,259(5091):87-91.
[36]LEWIS G F, CARPENTIER A, ADELI K. Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes [J]. Endocr Rev,2002,23 (2):201-229.
[37]Peraldi P, Hotamisligil GS, Buurman WA, et al. Tumor necrosis factor (TNF)-alpha sphingomyelinase [J]. J Biol Chem,1996,271(7):13018-13022.
[38]Begum N, Ragolia L, Srinivasan M. Effect of tumor necrosis factor-alpha on insulin-stimulated mitogen-activated protein kinase cascade in cultured rat skeletal muscle cells [J]. Eur J Biochem,1996,238(1):214-220.
[39]Li Z, Yang S, Lin H, Huang J, et al. Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease [J]. Hepatology, 2003,37(2):343-350.
[40]甄真,周俊英,刘金星,等.IL-6和SIL-6R在病毒性肝炎中的关系及其致病作用[J].世界华人消化杂志,2000,8(12)：1434～1435.
[41]高春芳.肥胖相关肝病的常见生物化学改变[J].中华肝脏病杂志,2004,12(7)：433～434.
[42]Alwayn IP, Andersson C, Lee S, et al. Inhibition of matrix metallop roteinases increases PPAR-alpha and IL-6 and p revents dietary-induced hepatic steatosis and injury in a murine model [J]. Am J Physiol Gastrointest Liver Physiol,2006,291(6): 1011-1009.
[43]Hui JM, Hodge A, Farrell GC, et al. Beyond insulin resistance in NASH:TNF-alpha or adiponectin [J]? Hepatology,2004,40(1):46-54.
[44]Farrell GC. Signalling links in the liver:knitting SOCS with fat and Inflammation [J]. J Hepatol,2005,43(1):193～196.
[45]Kim HJ, Higashimori T, Park SY, et al. Differential effects of interleukin-6 and-10 on skeletal muscle and liver insulin action in vivo [J]. Diabetes,2004,53(4):1060-1067.
[46]Lutchman G, Prom rat K, KleinerDE, et al. Changes in serum adipokine levels during pioglitazone treatment for nonalcoholic steato-hepatitis:relationship to histological imp rovement [J]. Clin Gastroenterol Hepatol,2006,4:1048-1052.
[47]Jepsen P, Vilstrup H, Mellemkjaer L, et al. Prognosis of patients with a diagnosis of fatty liver--a registry based cohort study [J].Hepatogastroenterology,2003,50 (54):2101～2104.
[48]谢伶俐,周力,李丽滨.TNF-a和IL-6在非酒精性脂肪性肝病患者血清中的水平及意义[J].世界华人消化杂志,2010,18(14)：1492～1496.
[49]Shoelson SE, Herrero L, Naaz A. Obesity, inflammation, and insulin resistance [J]. Gastroenterology,2007,132 (6):2169-2180.
[50]Choi S, Diehl AM. Role of inflammation in nonalcoholic steatohepatitis [J]. Curr Opin Gastroenterol,2005,21(6):702-707.
[51]王欣,张明威,孙淑艳,等.酒精性肝病患者血清NO、TNF-α和IL-6的检测及意义[J].临床肝胆病杂志,2000,16(3)：163～164.
[2]范建高,蔡晓波.非酒精性脂肪性肝病促进动脉粥样硬化的发生[J].中国动脉硬化杂志,2008,16(1)：1～3.
[3]范建高.非酒精性脂肪肝与代谢综合征[J].国外医学内分泌学分册,2002,22(5)：273～275.
[4]Clark JM, Diehl AM. Defining nonalcoholic fatty liver disease:implication for epidemiologic studies [J]. Gastroenterogy,2003,124(1):248～250.
[5]马晓燕.益气化痰消癖法治疗脂肪肝临床研究[J].山西中医药研究,2000,3(16)：32.
[6]范建高.酒精性与非酒精性脂肪性肝病[J].中华肝脏病杂志,2003,11(11)：692.
[7]卢晓岚,陶明,罗燕,等.饮酒与肝病流行病学调查[J].中华肝脏病杂志,2002,10(6)：467～468.
[8]曾民德脂肪肝发病机制”二次打击”假设[J].肝脏,2001,6(3)：14.
[9]Day CP, James OF. Steatohepatitis:a tale of two "hits" [J]? Gastroenterology,1998, 114(4):842～845.
[10]季光,张莉.重视非酒精性脂肪性肝病胰岛素抵抗的防治[J].世界华人消化杂志,2010,18(4)：1469～1473.
[11]Angulo P. Nonalcoholic fatty liver disease [J]. N Eng J Med,2002,346(16): 1221-1231.
[12]Medina Fernandez-Salazar LI, Garcia-Buey Moreno-Otero R. Approach to the pathogenesis and treatment of nonalcoholic steatohepatitis [J]. Diabetes Care,2004, 27(8):2057～2066.
[13]Rodriguez G, Gallego S, Breidenassel C, et al. Is liver transaminases assessment an appropriate tool for the screening of non-alcoholic fatty liver diseases in at risk obese children and adolescents [J]? Nutr Hosp,2010,25(5):712～717.
[14]Younossi ZM, Diehl AM, Ong JP. Nonalcoholic fatty liver disease:an agenda for clinical research [J]. Hepatology,2002; 35(4):746～752.
[15]Sanyal AJ. AGA technical review on nonalcoholic fatty liver disease [J]. Gastroenterology,2002,125(3):1705～1725.
[16]周卫东,杨亚玲,车志宏,等.非酒精性脂肪肝与超敏C反应蛋白、胰岛素抵抗的关系[J].中南大学学报：医学版,2008,33(7)：565～570.
[17]Yoneda M, Mawatar I H, Fujita K, et al. Highsensitivity C-reactive protein is an independent clinical feature of nonalcoholic steatohepatitis (NASH) and al-so of the severity of fibrosis in NASH [J]. J Gastroenterol,2007,42 (7):573-582.
[18]Poordad FF. The role of leptin in NAFLD:contender or pretender [J]? J Clin Gastroenterology,2004,38(10):841～63.
[19]Angulo P, Alba LM, Petro Vic LM. Leptin, insulin resistance, and liver fibrosis in human nonalcoholic fatty liver disease [J]. J Hepatol,2004,41(6):943～949.
[20]Alwayn IP, Andersson C, Lee S, et al. Inhibition of matrix metalloproteinases increases PPAR-alpha and IL-6 and p revents dietary-induced hepatic steatosis and injury in a murine model [J]. Am J Physiology Gastrointestinal Liver Physiology, 2006,291(6):1011-1009.
[21]Eiserich J P, Patel R P, Odonnel V B. Pathophysiology of nitric oxide and related species; free radical reactions and modification of biomolecules[J]. Mol Aspects Med, 1998,19(4-5):221～357.
[22]周荣根.脂肪肝与OX-LDL异常的中医分型治疗[J].云南中医中药杂志,2005,26(6)：64～65.
[23]Zimran A, Wasser G, Forman L, et al. Effect of ozone on red blood cell enzymes and intermediates [J]. Acta Haematol,2000,102 (3):148～151.
[24]Larini A, Bianchi L, Bocci V. The ozone tolerance:Enhancement of antioxidant enzymes is ozone dose dependent in Jurkat cells [J]. Free Radic Res,2003,37 (11): 1163-1168.
[25]Zamora ZB, Borrego A, Lopez OY, et al. Effects of ozone oxidative preconditioning on TNF-alpha release and antioxidant prooxidant intracellular balance in mice during endot oxic shock [J]. Mediators Inflamm,2005,2005 (1):16～22.
[26]郭亚兵.医用臭氧在内科临床中的应用[J].中华实验和临床感染病杂志(电子版),2008,2(1)：106.
[27]中华医学会肝脏病学会脂肪肝和酒精性肝病学组.非酒精性脂肪性肝病诊疗指南[J].肝脏,2006,11(11)：68～70.
[28]陈言东,党彤,孟宪梅.脂肪肝患者血清瘦素水平研究[J].包头医学院学报,2010,26(1)：42～44.
[29]Bugianesi E. Leone N, Vanni E, et al. Expanding t he natural history of nonalcoholic steatohepatitis:from cryptogenic cirrhosis to hepatocellular carcinoma [J]. Gast roenterology,2002,123 (1):134～140.
[30]E.Bugianesi MD. nonalcoholic Steatohepatitis and cancer [J]. Clinics in Liver Desease,2007,11(1):191～207.
[31]胡中伟,郭家伟,邓西龙.非酒精性脂肪肝与血清瘦素和胰岛素抵抗关系[J].南方医科大学学报,2006；26(6)：853～855.
[32]Sanyal AJ, Campbell-Sargent C, Mishahi F, et al. Non-alcoholic steatohepatitis: Association of insulin resistance and mitochondrial abnoemalities [J]. Gastroenterology,2001,120 (5):1183～1193.
[33]Gornicki A, Gutsze A. In vitro effects of ozone on human erythrocyte emembranes: an EPR study [J]. Acta Biochim Pol,2000,47 (4):963-971.
[34]Tsukamoto H, Rippe R, Niemela O. Roles of oxidative stress in activation of Kupffer and Ito cells in liver fibro genesis [J]. J Gast rent-roll Hepatol,1995; 10 (Supple l):S50-52.
[35]乔汗晨.非酒精性脂肪肝病研究进展[J].新乡医学院学报,2006,23(6)：630～634.
[36]Lieber CS. New concepts of the alcoholic liver disease lead to noveltreatments [J]. Cuur Gast roenterol Rep,2004,6:60～65.
[37]韩萍,成军,李莉.非酒精性脂肪肝炎的研究[J].世界华人消化杂志,2002,10(9)：1038～1039.
[38]成军,李莉,张玲霞,陈菊梅.丙型肝炎病毒感染与脂类代谢的相关性[J].肝脏2002；7：56～58.
[39]Weltman MO, Farrell GC, Liddle C. Increased hepatocyteCYP2El expression in a rat nutritional model of hepatic steatosis with inflammation [J]. Gastroenterology 1996; 111:1645～1650.
[40]吴勤,成军,李莉.酒精性脂肪肝的研究[J].世界华人消化杂志,2002,10(9)：1037～1038.
[41]Choudhury J, Sanyal AJ. Insulin resistance and the pathogenesis of nonalcoholic fatty liver disease [J]. Clin liver Dis,2004,8(3):575～594.
[42]Saxena N K, Ikeda K, Rockeyd C, et al. Leptin in hepatic fibrosis:evidence for increased collagen Production in stellate cells and lean littermates of obPob mice [J]. Hepatol,2002,35(4):762～771.
[43]Wang MY, Zhou YT, Newgard CB, et al. A novel leptin receptor isoform in rat [J]. F EBS Lett,1996,392(2):87～90.
[44]CHITTURI S, ABEYGUNADEKERA S, FARRELL GC, et al. NASH and insulin resistance:Insulin hypersecretion and specific association with the insulin resistance syndrome [J]. Hepatol,2002,35(2):497～499.
[45]Barek J, Bartos J, Galuska J, et al. Expression of ob-gene coding the production of the hormone leptin in hepatocytes of liver with steatosis [J]. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub,2001,145 (1):15-20.
[46]马向华,王维敏.非酒精性脂肪肝患者瘦素抵抗和胰岛素抵抗研究[J].中华肝脏病杂志,2004,12(11)：651～655.
[47]Bethanis SK, Theohari's SE. Leptin in the Field of Hepatic FIbrosis:A Pivotal or an Incidental Player [J]? Dig Dis Sci 2006,51(10):1685-1696.
[48]Lydatakis H, Hager IP, Kostadelou E,et al. Noninvasive markers to predict the liver fibrosis in non-alcoholic fatty liver disease [J]. Liver Int,2006,26(7):864～871.
[49]Namecz M, Preiniger K, Englishch R, et al. Acute effect of leptin on hepatic glycogenolysis and gluconeogenesis in perfused rat liver [J]. Hepatology,1999,29 (1); 166～172.
[50]Dong H, Lu FE, Gao ZQ, et al. Effect s of emodin ont reating murine nonalcoholic fatty liver induced by high caloric laboratory chaw [J]. World J Gast roenterol,2005, 11 (9):1339～1344.
[51]农兵,罗和生.瘦素在实验性大鼠肝纤维化发生中的作用机制初探[J].内科,2007,2(1)：7～11.
[52]Ibabe A, Bilbao E, Cajaraville MP, et al. Expression of peroxisome proliferator Oactivated receptors in zebrafish (Danio rerio) depending on gender and developmental stage [J]. Histochem Cell Biol,2005,123 (1):75-87.
[53]杨辉,李瑜元,江庆澜,等.瘦素与非酒精性脂肪肝的关系[J].广州医学院学报,2005,33(5)：10～13.
[54]Chitturi S, Farrell GC, Hashimoto E, et al. Non-alcoholic fatty liver disease in the Asia-Pacific region:definitions and overview of proposed guidelines [J]. J Gastroenterol Hepatol,2007,22(6):778-87.
[55]Chitturi S, Farrell GC. Etiopathogenesis of nonalcoholic steatohepatitis [J]. Semin Liver Dis,2001; 21(1):27-41.
[56]丁佳,范竹萍.非酒精性脂肪肝和心血管疾病[J].国际消化病杂志,2008,28(4)：320～322.
[57]Bugianesi E, Manzini P, D'Antico S, et al. Relative contribution of iron burden, HFE mutations, and insulin resistance to fibrosis in nonalcoholic fatty liver[J]. Hepatology, 2004; 39(6):179～187.
[58]卫建筠,杨海红,曾文铤.非酒精性脂肪肝患者血清瘦素水平与肝纤维化关系研究[J].临床医学工程,2009,16(4)：46～47.
[59]Cortez-Pinto H, Camilo ME, Baptista A, et al. Non-alcoholic fatty liver, Another feature of the metabolic syndrome [J]. Clin Nut r,1999,18(6):353～358.
[60]Chen X, Osborne M C, Rybczynski P J, et al. Pharmacological profile of a novel, non-OTZD PPAR-gamma agonist [J]. Diabetes Obes Metab,2005,7(5):536～546.
[61]黄伟,季峰,姜玲玲,等.脂肪肝患者血清瘦素水平检测及其与发病的关系[J].中华检验医学杂志,2004,27(2)：106.
[62]Marsh DJ, Hollopeter G, Huszar D, et al. Response of neuropeptide Y deficient mice to feeding effectors [J]. Nat Genet,1998,25(75-76):119～122.
[63]Cohen B, Novick D, Rubinstein M. Modulation of insulin activity by leptin [J]. Science,1996,274 (5290):1185～1188.
[64]Laubner K, Kieffer T J, Lam N T, et al. Inhibition of prepro-insulin gene expression by leptin induction of suppressor of cytokine signaling 3 in pancreatic beta-cells [J]. Diabetes,2005,54:3410-3417.
[65]Considine RV, Sinha MK, Heiman ML, et al. Serum immunoreactive-leptin concentrations in normal-weight and obesehumans [J]. N Eng JMed,1996,334(5): 292～296.
[66]魏良洲,杨正武.瘦素、胰岛素在非酒精性脂肪肝发病中的作用[J].临床肝胆病杂志,2006,22(1)：71～73.
[67]Beckman JS, KoppenolWH. Nitric oxide, superoxide, and peroxynitrite:the good, the bad, and ugly [J]. Am J Physi2ol,1996; 271 (5):C1424-1437.
[68]Ekstedt M, Franzen LE, Mathiesen UL. Long term followup of patients with NAFLD and elevated liver enzymes [J]. Hepatology,2006,44:865～873.
[69]Raij L. Nitric oxide in the pathogenesis of cardiac disease [J]. Clin Hypertens (Greenwich),2006; 8 (12 Supp 1):S30-39.
[70]Cengel A, Sahinarslan A. Nitric oxide and cardiovascular system [J]. Anadolu Kardiyol Derg,2006; 6 (4):364～368.
[71]王秀红,路方红.内皮素、一氧化氮与心血管疾病[J].中国慢性病预防与控制,2005,13(3)：139～141.
[72]Beckman JS, KoppenolWH. Nitric oxide, superoxide, and peroxynitrite:the good, the bad, and ugly [J]. Am J Physi2ol,1996; 271(5):C1424～1437.
[73]吕天英,卢震亚.非酒精性脂肪性肝病大鼠肝组织NO和iNOS的变化[J].浙江预防医学,2009,21(4)：9～11.
[74]Sanchez-M, argalet V, Martin-Romero C.Human leptin signaling in human peripheral blood mononuclear cells:Activation of the JAK-STAT pathway [J].Cell Immuno, 2001, (211):30-36.
[75]Yin XY, Jiang JM, Liu JY, et al. Effects of endogenous nitric oxide induced by 5-fluorouracil and L-Arg on liver carcinoma in nude mice [J]. World J Gastroenterol, 2007,13 (46):6249～6253.
[76]温继梨,承喜凤,陈凤英.一氧化氮与心血管疾病[J].内蒙古医学院学报,2008,30(3)：223～228.
[77]Pratico D, Lawson JA, Rokach J, et al. The isoprostanes in biology and medicine. Trends Endocrinol Metab,2001,12(6):243～7.
[78]Janssen LJ. Isoprostanes:an overview and putative roles in pulmonary pathophysiology. Am J Physiol Lung Cell Mol Physiol.2001,280(6):L1067-82.
[79]Rader D J. Effect of insulin resistance, dyslip idemia, and intraabdominal adiposity on the development of cardiovascular disease and diabetesmellitus [J]. Am J Med, 2007,120(3 Supp 11):S12-18.
[80]Feng R, HeW, Ochi H, et al. Ozone exposure impairs antigen specific immunity but activates IL-7 induced proliferation of CD4-CD8- thymocytes in BALB/c mice [J]. J Toxicol Environ Health A,2006,69 (16):1511-1526.
[81]Bocci V, Luzzi E, Corradeschi F, et al. Studies on the biological effects of ozone:5. Evaluation of immunological parameters and tolerability in normal volunteers receiving ambulatory autohaemotherapy [J]. Biotherapy,1993-1994,7 (2):83～90.
[82]Merin O, Attias E, Elstein D, et al. Ozone administration reduces reperfusion injury in an isolated rat heart model [J]. J Card Surg,2007,22 (4):339-342.
[83]Zamora ZB, Borrego A, Lopez OY, et al. Effects of ozone oxidative p reconditioning on TNF-alpha release and antioxidant prooxidant intracellular balance in mice during endo-toxic shock [J]. Mediators Inflamm,2005,2005 (1):16～22.
[84]Peralta C, Xaus C, Barttrons R, et al. Effect of ozone treatment on reactive oxygen species and adenosine production during hepatic is chemiareperfusion [J]. Free Radic Res,2000,33 (5):595～605.
[1]Day CP, James OF. Steatohepatitis:a tale of two "hits" [J]? Gastroenterology, 1998,114 (4):842～845.
[2]Choudhury J, Sanyal AJ. Insulin resistance and the pathogenesis of nonalcoholic fatty liver disease [J]. Clin liver Dis,2004,8(3):575～594.
[3]王征,刘东戈.非酒精性脂肪性肝炎与细胞因子[J].世界华人消化杂志,2007,15(3)：266～271.
[4]SAXENA N K, IKEDA K, ROCKEYD C, et al. Leptin in hepatic fibrosis:evidence for increased collagen Production in stellate cells and lean littermates of obPob mice [J]. Hepatol,2002,35(4):762-771.
[5]Wang MY, Zhou YT, Newgard CB, et al. A novel leptin receptor isoform in rat [J]. F EBS Lett,1996,392(2):87-90.
[6]CHITTURI S, ABEYGUNADEKERA S, FARRELL GC, et al. NASH and insulin resistance:Insulin hypersecretion and specific association with the insulin resistance syndrome [J]. Hepatol,2002,35(2):497-499.
[7]杨辉,李瑜元,聂玉强,等脂肪组织瘦素基因与非酒精性脂肪肝的研究[J].中华肝脏病杂志,2006,11(14)：828～831.
[8]HUAN J N, LI J, HAN Y, et al. Adipocyte selective reduction of the leptin receptors induced by antisense RNA leads to increased adiposity, dyslipidemia, and insulin resistance [J]. J Biol Chem,2003,278(46):45638-45650.
[9]马向华,王维敏.非酒精性脂肪肝患者瘦素抵抗和胰岛素抵抗研究[J].中华肝脏病杂志,2004,12(11)：651～655.
[10]Saxena NK, Ikeda K, Rockey DC, et al. Leptin in hepatic fibrosis:evidence for Increased collagen production in stellate cells and lean littermates of ob/ob mice [J]. Hepatology,2002,35 (4):762-771.
[11]Bethanis SK, Theohari's SE. Leptin in the Field of Hepatic Fibrosis:A Pivotal or an Incidental Player [J]? Dig Dis Sci 2006,51(10):1685-1696.
[12]Lydatakis H, Hager I P, Kostadelou E, et al. Noninvasive markers to predict the liver fibrosis in non-alcoholic fatty liver disease [J]. Liver Int,2006,26(7):864-871.
[13]Chitturi S, Farrell G, Frost L, et al. Serum leptin in NASH correlates with hepatic steatosis but not fibrosis:a manifestation of lipotoxicity [J]? Hepatology,2002,36(2): 403-409.
[14]杨辉,李瑜元,江庆澜,等.瘦素与非酒精性脂肪肝的关系[J].广州医学院学报,2005,33(5)：10～13.
[15]Scherer PE, Williams S, Fogliano M, et al. A novel serum protein similar to CIq, produced exclusively in adipocytes [J]. J Biol Chem,1995,270(45):26746-26749.
[16]Yamauchi T, Kamon J, Ito Y, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects [J]. Nature,2004,43(7021):762-769.
[17]Targher G, Bertolini L, Rodella S, et al. Associations between plasma adiponectin concentrations and liver histology in patients with nonalcoholic fatty liver disease [J]. Clin Endocrinol (Oxf),2006,64:679-683.
[18]Abiru S, Migita K, Maeda Y, et al. Serum cytokine and soluble cytokine receptor levels in patients with non-alcoholic steatohepatitis [J]. Liver Int,2006,26(1):39～45.
[19]Claudio P, Giorgio S, Walter E. Plasma adiponectin is decreased in nonalcoholic fatty liver disease [J]. Eur J Endocrinol,2004,152(1):113-118.
[20]Xu A,Wang Y, Keshaw H, et al. The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice [J]. Eur J Endoerinol, 2003,112(1):91-100.
[21]Vuppalanchi R, Marri S, Kolwankar D, et al. Is adiponectin involved in the pathogens is of nonalcoholic steatohepatitis? A preliminary human study [J]. J Clin Gastroenterology,2005,39(3):237-242.
[22]Yang H, Li YY, Nie YQ, Zhou YJ, DU YL, Sha WH, Hng Y. The relationship between insulin resistance and adiponectin gene expression in nonalcoholic fatty liver disease [J]. Zhonghua Ganzangbing Zazhi 2007; 15:525-528.
[23]Steppan CM, Baily ST, Bhat S, et al.The hormone resisistin links obesity to diabetes [J]. Nature,200,409(1):307-312.
[24]Steppan CM, Baily ST, Bhat S, et al. he hormone resisistin links obesity to diabetes [J].Regul Integr Comp Physiol,2005,288(5):1220-1225.
[25]Steppan CM, Bailey ST, Bhat S, et al. The hormone resistin links obesity to diabetes [J]. Nature,2001,49(18):307-312.
[26]杨文慧,赵和平.抵抗素与非酒精性脂肪性肝病[J].国际内科学杂志,2007,34(8)：452～455.
[27]Weisberg SP, McCann D, Desai M, et al. Obesity is associated with macrophage accumulation in adipose tissue [J]. J Clin Invest,2003,112(12):1796-1808.
[28]Smith SR, Bai F, Charbonneau C, et al. A promoter genotype and oxidative stress potentially link resistin to human insulin resistance [J]. Diabetes,2003,52(7): 1611-1618.
[29]STEPPAN C M, LAZAR M A. The current biology of resistin [J]. J Intern Med,2004, 255(4):439-447.
[30]Hartman HB, Hu X, Tyler KX, et al. Mechanisms regulating adipicyte expression of resistance [J]. J Biol Chem.2002,277(22):19754-19761.
[31]钱林,胡小宣.非酒精性脂肪肝分子发病机制的研究进展[J].世界华人消化杂志,2008,16(25)：2848～2852.
[32]王莹,蔡东联脂肪细胞因子与非酒精性脂肪肝相关性研究进展[J].国外医学卫生学分册,2008,35(5)：296-299.
[33]Haukeland JW, Damas JK, Konopski Z, et al. Systemic inflammation in nonalcoholic fatty liver disease is characterized by elevated levels of CCL2 [J]. J Hepatol 2006,44: 1167-1174.
[34]Wong VW, Hui AY, Tsang SW, et al. Metabolic and adipokine profile of Chinese patients with nonalcoholic fatty liver disease [J]. Clin Gastroenterol Hepatol,2006,4 (9):1154-1161.
[35]HOTAMISLIGIL G S, SHARGILL N S, SPIEGELMAN B M. Adipose expression of tumor necrosis factoralpha: direct role in obesity linked insulin resistance [J]. Sci, 1993,259(5091):87-91.
[36]LEWIS G F, CARPENTIER A, ADELI K. Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes [J]. Endocr Rev,2002,23 (2):201-229.
[37]Peraldi P, Hotamisligil GS, Buurman WA, et al. Tumor necrosis factor (TNF)-alpha sphingomyelinase [J]. J Biol Chem,1996,271(7):13018-13022.
[38]Begum N, Ragolia L, Srinivasan M. Effect of tumor necrosis factor-alpha on insulin-stimulated mitogen-activated protein kinase cascade in cultured rat skeletal muscle cells [J]. Eur J Biochem,1996,238(1):214-220.
[39]Li Z, Yang S, Lin H, Huang J, et al. Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease [J]. Hepatology, 2003,37(2):343-350.
[40]甄真,周俊英,刘金星,等.IL-6和SIL-6R在病毒性肝炎中的关系及其致病作用[J].世界华人消化杂志,2000,8(12)：1434～1435.
[41]高春芳.肥胖相关肝病的常见生物化学改变[J].中华肝脏病杂志,2004,12(7)：433～434.
[42]Alwayn IP, Andersson C, Lee S, et al. Inhibition of matrix metallop roteinases increases PPAR-alpha and IL-6 and p revents dietary-induced hepatic steatosis and injury in a murine model [J]. Am J Physiol Gastrointest Liver Physiol,2006,291(6): 1011-1009.
[43]Hui JM, Hodge A, Farrell GC, et al. Beyond insulin resistance in NASH:TNF-alpha or adiponectin [J]? Hepatology,2004,40(1):46-54.
[44]Farrell GC. Signalling links in the liver:knitting SOCS with fat and Inflammation [J]. J Hepatol,2005,43(1):193～196.
[45]Kim HJ, Higashimori T, Park SY, et al. Differential effects of interleukin-6 and-10 on skeletal muscle and liver insulin action in vivo [J]. Diabetes,2004,53(4):1060-1067.
[46]Lutchman G, Prom rat K, KleinerDE, et al. Changes in serum adipokine levels during pioglitazone treatment for nonalcoholic steato-hepatitis:relationship to histological imp rovement [J]. Clin Gastroenterol Hepatol,2006,4:1048-1052.
[47]Jepsen P, Vilstrup H, Mellemkjaer L, et al. Prognosis of patients with a diagnosis of fatty liver--a registry based cohort study [J].Hepatogastroenterology,2003,50 (54):2101～2104.
[48]谢伶俐,周力,李丽滨.TNF-a和IL-6在非酒精性脂肪性肝病患者血清中的水平及意义[J].世界华人消化杂志,2010,18(14)：1492～1496.
[49]Shoelson SE, Herrero L, Naaz A. Obesity, inflammation, and insulin resistance [J]. Gastroenterology,2007,132 (6):2169-2180.
[50]Choi S, Diehl AM. Role of inflammation in nonalcoholic steatohepatitis [J]. Curr Opin Gastroenterol,2005,21(6):702-707.
[51]王欣,张明威,孙淑艳,等.酒精性肝病患者血清NO、TNF-α和IL-6的检测及意义[J].临床肝胆病杂志,2000,16(3)：163～164.