平均血小板体积与非酒精性脂肪性肝病的关系研究
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摘要
目的:血小板平均体积(mean platelet volume, MPV)是评价血小板活性的一种指标。血小板活化、聚集是冠心病(coronary heart disease, CHD)发病机制的中心环节。非酒精性脂肪性肝病(non-alcoholic fatty liver disease, NAFLD)在普通人群中的发病率高达1/3,并且是心脏代谢性疾病的主要危险因素,常常合并有腹型肥胖、2型糖尿病(T2DM)及其它代谢综合征(metabolic syndrome, MS)亚组分。本研究的目的就是初步阐明NAFLD患者MVP的变化规律。
方法:检测50例正常人和例NAFLD患者的MPV水平,并进行统计学分析。
结果:①NAFLD组与正常对照组相比PC减少而MPV升高(10.43±1.14 vs. 9.09±1.25; p < 0.001)。②MPV与谷草转氨酶(AST) (r=0.186, p < 0.042)、谷丙转氨酶(ALT)(r=0.279; p=0.002)及NAFLD(r=0.492; p < 0.001)正相关;而与血小板计数(PC)(r=?0.26; p=0.004)、肌酐(Cr)(r=?0.255; p=0.005)负相关。③以MPV为应变量,性别、年龄、收缩压(SBP)、舒张压(DBP)、NAFLD、MPV、空腹血糖(FPG)、总胆固醇(TC)、甘油三酯(TG)、PC、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、Cr、AST、ALT为自变量,进行逻辑回归分析,结果表明NAFLD是MPV的独立预测指标(Odds Ratio (OR) 21.98) [95% confidence interval (CI): 2.404–201.048; p= 0.006]。
结论:NAFLD患者有较大的MPV值,并可在一定程度上预测心血管疾病(cardiovascular disease, CVD)的发生。
Objective: Mean platelet volume (MPV) is an indictor of platelet activation. Platelet activation and aggregation are central processes in the pathophysiology of coronary heart disease(CHD). Non-alcoholic fatty liver disease (NAFLD) is present up to one–third of the general population and the majority of patients with cardio-metabolic risk factors such as abdominal obesity, type 2 diabetes and other components of the metabolic syndrome (MS). The aim of the current study was to investigate the MPV in patients who had NAFLD.
Methods: The level of MPV was measured in 50 normal controls and 65 patients with NAFLD. A statistically analysis of the data was conducted.
Results:①MPV values of the patients with NAFLD and of the patients without fatty liver disease were compared.Among biochemical variables, fasting plasma glucose and triglyceride were significantly higher in the NAFLD group. NAFLD cases also had lower platelet count and higher MPV (10.43±1.14 vs. 9.09±1.25; p < 0.001, respectively). ②MPV was positively correlated with AST (r=0.186, p < 0.042), ALT level (r=0.279; p= 0.002) and the presence of NAFLD (r=0.492; p < 0.001) but negatively correlated with platelet number (r=?0.26; p=0.004) and creatinine (r=?0.255; p=0.005).③In logistic regression analysis [age, gender, NAFLD, high-density lipid cholesterol (HDL-C), systolic and diastolic blood pressure (SBP, DBP), triglyceride (TG) and fasting plasma glucose (FPG) were used as covariates] only NAFLD was found to be the independent predictor of MPV (Odds Ratio (OR) 21.98) [95% confidence interval (CI): 2.404–201.048; p= 0.006].
Conclusions: Patients with NAFLD have higher MPV. It may,to some extence, have prognostic value in NAFLD patients indicating a possible cardiovascular disease (CVD).
方法:检测50例正常人和例NAFLD患者的MPV水平,并进行统计学分析。
结果:①NAFLD组与正常对照组相比PC减少而MPV升高(10.43±1.14 vs. 9.09±1.25; p < 0.001)。②MPV与谷草转氨酶(AST) (r=0.186, p < 0.042)、谷丙转氨酶(ALT)(r=0.279; p=0.002)及NAFLD(r=0.492; p < 0.001)正相关;而与血小板计数(PC)(r=?0.26; p=0.004)、肌酐(Cr)(r=?0.255; p=0.005)负相关。③以MPV为应变量,性别、年龄、收缩压(SBP)、舒张压(DBP)、NAFLD、MPV、空腹血糖(FPG)、总胆固醇(TC)、甘油三酯(TG)、PC、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、Cr、AST、ALT为自变量,进行逻辑回归分析,结果表明NAFLD是MPV的独立预测指标(Odds Ratio (OR) 21.98) [95% confidence interval (CI): 2.404–201.048; p= 0.006]。
结论:NAFLD患者有较大的MPV值,并可在一定程度上预测心血管疾病(cardiovascular disease, CVD)的发生。
Objective: Mean platelet volume (MPV) is an indictor of platelet activation. Platelet activation and aggregation are central processes in the pathophysiology of coronary heart disease(CHD). Non-alcoholic fatty liver disease (NAFLD) is present up to one–third of the general population and the majority of patients with cardio-metabolic risk factors such as abdominal obesity, type 2 diabetes and other components of the metabolic syndrome (MS). The aim of the current study was to investigate the MPV in patients who had NAFLD.
Methods: The level of MPV was measured in 50 normal controls and 65 patients with NAFLD. A statistically analysis of the data was conducted.
Results:①MPV values of the patients with NAFLD and of the patients without fatty liver disease were compared.Among biochemical variables, fasting plasma glucose and triglyceride were significantly higher in the NAFLD group. NAFLD cases also had lower platelet count and higher MPV (10.43±1.14 vs. 9.09±1.25; p < 0.001, respectively). ②MPV was positively correlated with AST (r=0.186, p < 0.042), ALT level (r=0.279; p= 0.002) and the presence of NAFLD (r=0.492; p < 0.001) but negatively correlated with platelet number (r=?0.26; p=0.004) and creatinine (r=?0.255; p=0.005).③In logistic regression analysis [age, gender, NAFLD, high-density lipid cholesterol (HDL-C), systolic and diastolic blood pressure (SBP, DBP), triglyceride (TG) and fasting plasma glucose (FPG) were used as covariates] only NAFLD was found to be the independent predictor of MPV (Odds Ratio (OR) 21.98) [95% confidence interval (CI): 2.404–201.048; p= 0.006].
Conclusions: Patients with NAFLD have higher MPV. It may,to some extence, have prognostic value in NAFLD patients indicating a possible cardiovascular disease (CVD).
引文
[1] Schreuder TC, Verwer BJ, van Nieuwkerk CM, et al. Nonalcoholic fatty liver disease:An overview of current insights in pathogenesis, diagnosis and treatment[J]. World J Gastroenterol. 2008, 14: 2474–2486
[2] Hamaguchi M, Kojima T, Takeda N, et al. The metabolic syndrome as a predictor of nonalcoholic fatty liver disease[J]. Ann Intern Med. 2005, 143: 722–728
[3] Socha P, Wierzbicka A, Neuhoff M. Nonalcoholic fatty liver disease as a feature of the metabolic syndrome[J]. Rocz Panstw Zakl Hi. 2007, 58(1):129-137
[4] Sattar N, Scherbakova O, Ford I, et al. Elevated alanine aminotransferase predicts new-onset type 2 diabetes independently of classical risk factors, metabolic syndrome, and C-reactive protein in the West of Scotland Coronary Prevention Study[J]. Diabete. 2004, 53: 2855–2860
[5] Hanley AJ, Williams K, Festa A,et al. Liver markers and development of the metabolic syndrome: the Insulin Resistance Atherosclerosis Study[J].Diabete. 2005, 54: 3140–3147
[6] Tsiara S, Elisaf M, Jagroop IA, et al. Platelets as predictors of vascular risk: Is there a practical index of platelet activity?[J]. Clin Appl Thromb Hemost. 2003, 9: 177–190
[7] Pizzulli L, Yang A, Martin JF, et al. Changes in platelet size and count in unstable angina compared tostable angina or non-cardiac chest pain[J]. Eur Heart J. 1998, 19: 80–84
[8] Endler G, Klimesch A, Sunder-Plassmann H, et al. Mean platelet volume is an independent risk factor for myocardial infarction but not for coronary artery disease[J].Br J Haemato. 2002, 117(2):399-404
[9]中华医学会肝病学分会脂肪肝和酒精性肝病学组.非酒精性脂肪性肝病诊断标准[J].中华肝脏病杂志. 2003, 11(2): 71
[10] Angelico F, Del Ben M, Conti R, et al. Insulin resistance, the metabolic syndrome, and nonalcoholic fatty liver disease[J]. J Clin Endocrinol Metab. 2005, 90:1578–1582
[11] Marchesini G, Bugianesi E, Forlani G, et al. Nonalcoholic fattyliver, steatohepatitis, and the metabolic syndrome[J]. Hepatology. 2003, 37: 917–923
[12] Mirbagheri SA, Rashidi A, Abdi S, et al. Liver: An alarm for the heart?[J]. Liver Int. 2007, 27: 891–894
[13] Targher G, Bertolini L, Padovani R, et al. Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients[J]. Diabetes Care. 2007, 30: 1212–1218
[14] Targher G, Bertolini L, Rodella S, et al. Nonalcoholic fatty liver disease is independently associated with an increased incidence of cardiovascular events in type 2 diabetic patients[J]. Diabetes Care. 2007, 30: 2119–2121
[15] Thompson CB, Jakubowski JA. The pathophysiology and clinical relevance of platelet heterogeneity[J]. Blood. 1998, 72: 1–8
[16] Martin JF, Trowbridge EA, Salmon G, et al. The biological significance of platelet volume: Its relationship to bleeding time, thromboxane B2 production and megakaryocyte nuclear DNA concentration[J]. Thromb Res. 1983, 32: 443–460.
[17] Sewell R, Ibbotson RM, Philips R. High mean platelet volume after myocardial infarction: Is it due to consumption of small platelets?[J]. Br Med J. 1984, 289: 1576–1580
[18] Zuberi B, Akhtar N, Afsar S. Comparison of mean platelet volume in patients with diabetes mellitus, impaired fasting glucose and non-diabetic subjects[J]. Singapore Med J. 2008, 49(2):114-116
[19] Coban E, Ozdogan M, Yazicioglu G, et al. The mean platelet volume in patients with obesity[J]. Int J Clin Pract. 2005, 59: 981–982
[20] Kong AP, Choi KC, Cockram CS, et al. Independent associations of alanine aminotransferase (ALT) levels with cardiovascular risk factor clustering in Chinese adolescents[J]. J Hepato. 2008, 49: 115–122
[21] Wang CC, Lin SK, Tseng YF, et al. Elevation of serum aminotransferase activityincreases risk of carotid atherosclerosis in patients with non-alcoholic fatty liver disease[J]. J Gastroenterol Hepato. 2009, 24: 1411–1416
[1] Raszeja-Wyszomirska J, Lawniczak M, Marlicz W, et al. Non-alcoholic fatty liver disease--new view[J]. Pol Merkur Lekarski, 2008, 24(144): 568-571.
[2] Keishi K, Susumu T, Tomoji N, et al. Angiotensin II participates in hepatic inflammation and fibrosis through MCP-1 expression[J]. Dig Dis Sci, 2005, 5(50): 942–948.
[3] Yokohama S , Yoneda M, Haneda M, et al.Therapeutic efficacy of an angiotensin II receptor antagonist in patients with nonalcoholic steatohepatitis[J]. J Hepatol, 2004, 40(5): 1222-1225.
[4] Paschos P, Paletas K. Non alcoholic fatty liver disease and metabolic syndrome[J]. Hippokratia, 2009, 13(1): 9–19.
[5] Sudheer K, Mantena A, King K, et al. Mitochondrial dysfunction and oxidative stress in the pathogenesis of alcohol and obesity induced fatty liver diseases[J]. Free Radical Biology and Medicine, 2008, 44(7): 1259-1272.
[6] Cusi K. Role of insulin resistance and lipotoxicity in non-alcoholic steatohepatitis[J]. Clin Liver Dis, 2009, 13(4): 545-563.
[7] Santos R, Ferreira A. Angiotensin-(1-7) and the renin-angiotensin system[J]. Curr Opin Nephrol Hypertens, 2007, 16(2): 122–128.
[8] Herath C, Warner F, Lubel J, et al. Upregulation of hepatic angiotensin-converting enzyme 2 (ACE2) and angiotensin-(1-7) levels in experimental biliary fibrosis[J]. J Hepatol, 2007, 47(3): 387–395.
[9] Nogueira A, Souza S, Simoes E, et al. The pregnancy induced increase of plasma angiotensin -(1-7) is blunted in gestational diabetes[J]. Regul Pept, 2007, 141(1-3): 55–60.
[10] Walkíria W, Ant?nio R, Regina M, et al. Relationship between angiotensin(1-7) and angiot- ensin II correlates with hemodynamic changes in human liver cirrhosis[J]. World J Gastroenterol, 2009 ,15(20): 2512–2519.
[11] Bataller R, Sancho-Bru P, Ginès P, et al. Activated human hepatic stellate cells express the renin-angiotensin system and synthesize angiotensin II[J].Gastroenterology, 2003, 125(1): 117-25.
[12] Yang L, Bataller R, Dulyx J, et al. Attenuated hepatic inflammation and fibrosis in angiotensin type 1a receptor deficient mice[J]. J Hepatol, 2005, 43(2): 317–323.
[13] Hitoshi Y, Ryuichi N, Yasuhide I, et al. Losartan, an angiotensin-II type 1 receptor blocker, attenuates the liver fibrosis development of non-alcoholic steatohepatitis in the rat[J]. BMC Res Notes, 2009, 2: 70.
[14] Shimamoto K, Miura T. Metabolic syndrome[J]. Nippon Rinsho, 2009, 67(4): 771-776.
[15] Weir M. Effects of renin-angiotensin system inhibition on end-organ protection: can we do better?[J]. Clin Ther, 2007, 29(9): 1803-1824.
[16] Jorge E, Marina C, Gabriel C, et al. ACE inhibition and AT1 receptor blockade prevent fatty liver and fibrosis in obese zucker rats[J]. Obesity, 2008, 16(4): 770–776.
[17] Harrihar A, Pershadsingh, David M. PPAR Agonists: Potential as therapeutics for neovascular retinopathies[J]. PPAR Res, 2008, 2008: 164273.
[18] Ziemke F, Mantzoros C. Adiponectin in insulin resistance: lessons from translational rsearch[J]. Am J Clin Nutr, Epub 2009 Nov 11.
[19] Parsons C, Takashima M, Rippe R. Molecular mechanisms of hepatic fibrogenesis[J]. J Gastroenterol Hepatol, 2007, 22 Suppl 1: S79-84.
[20] Kitamura K, Tada S, Nakamoto N, et al. Rho/Rho kinase is a key enzyme system involved in the angiotensin II signaling pathway of liver fibrosis and steatosis[J]. J Gastroenterol Hepatol, 2007, 22(11): 2022-2033.
[21] Bataller R, Sancho-Bru P, Ginès P. Liver Fibrogenesis: A new role for the renin–angiotensin system[J]. Antioxid Redox Signal, 2005, 7(9-10): 1346-1355.
[22] Park D, Baik S, Choi Y, et al. Inhibitory effect of angiotensin blockade on hepatic fibrosis in common bile duct-ligated rats. Korean J Hepatol, 2007, 13(1): 61-69.
[23] Kim M, Baik S, Park D, et al. Angiotensin receptor blockers are superior to angiotensin -converting enzyme inhibitors in the suppression of hepatic fibrosis in a bile duct-ligated rat model[J]. J Gastroenterol, 2008, 43(11): 889-896.
[24] Ramon B, Pau S, Pere G, et al. Liver fibrogenesis: a new role for the renin–angiotensin system[J]. Antioxic Redox Signal, 2005, 7(9-10) : 1346–1355.
[25] Li X, Meng Y, Cai S, et al. Aldosterone stimulates alpha1-(1) procollagen mRNA expression in HSC via activation of ERK1/2 and AP-1[J]. Zhonghua Gan Zang Bing Za Zhi, 2005, 13(11): 815-818.
[26] Osterreicher C, Taura K, De -Minicis S, et al. Angiotensin-converting-enzyme 2 inhibits liver fibrosis in mice[J]. Hepatology, 2009, 50(3): 929-938.
[27] 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: 179-187.
[28] Osterreicher C, Taura K, De -Minicis S, et al. Angiotensin-converting-enzyme 2 inhibits liver fibrosis in mice[J]. Hepatology, 2009, 50(3): 929-938
[29] Pereira R, dos- Santos R, da -Costa D. Renin-angiotensin system in the pathogenesis of liver fibrosis[J]. World J Gastroenterol, 2009, 15(21): 2579-2586.
[30] Lubel J, Herath C, Burrell L, et al. Liver disease and the renin-angiotensin system: recent discoveries and clinical implications[J]. J Gastroenterol Hepatol, 2008, 23(9): 1327-1338.
[2] Hamaguchi M, Kojima T, Takeda N, et al. The metabolic syndrome as a predictor of nonalcoholic fatty liver disease[J]. Ann Intern Med. 2005, 143: 722–728
[3] Socha P, Wierzbicka A, Neuhoff M. Nonalcoholic fatty liver disease as a feature of the metabolic syndrome[J]. Rocz Panstw Zakl Hi. 2007, 58(1):129-137
[4] Sattar N, Scherbakova O, Ford I, et al. Elevated alanine aminotransferase predicts new-onset type 2 diabetes independently of classical risk factors, metabolic syndrome, and C-reactive protein in the West of Scotland Coronary Prevention Study[J]. Diabete. 2004, 53: 2855–2860
[5] Hanley AJ, Williams K, Festa A,et al. Liver markers and development of the metabolic syndrome: the Insulin Resistance Atherosclerosis Study[J].Diabete. 2005, 54: 3140–3147
[6] Tsiara S, Elisaf M, Jagroop IA, et al. Platelets as predictors of vascular risk: Is there a practical index of platelet activity?[J]. Clin Appl Thromb Hemost. 2003, 9: 177–190
[7] Pizzulli L, Yang A, Martin JF, et al. Changes in platelet size and count in unstable angina compared tostable angina or non-cardiac chest pain[J]. Eur Heart J. 1998, 19: 80–84
[8] Endler G, Klimesch A, Sunder-Plassmann H, et al. Mean platelet volume is an independent risk factor for myocardial infarction but not for coronary artery disease[J].Br J Haemato. 2002, 117(2):399-404
[9]中华医学会肝病学分会脂肪肝和酒精性肝病学组.非酒精性脂肪性肝病诊断标准[J].中华肝脏病杂志. 2003, 11(2): 71
[10] Angelico F, Del Ben M, Conti R, et al. Insulin resistance, the metabolic syndrome, and nonalcoholic fatty liver disease[J]. J Clin Endocrinol Metab. 2005, 90:1578–1582
[11] Marchesini G, Bugianesi E, Forlani G, et al. Nonalcoholic fattyliver, steatohepatitis, and the metabolic syndrome[J]. Hepatology. 2003, 37: 917–923
[12] Mirbagheri SA, Rashidi A, Abdi S, et al. Liver: An alarm for the heart?[J]. Liver Int. 2007, 27: 891–894
[13] Targher G, Bertolini L, Padovani R, et al. Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients[J]. Diabetes Care. 2007, 30: 1212–1218
[14] Targher G, Bertolini L, Rodella S, et al. Nonalcoholic fatty liver disease is independently associated with an increased incidence of cardiovascular events in type 2 diabetic patients[J]. Diabetes Care. 2007, 30: 2119–2121
[15] Thompson CB, Jakubowski JA. The pathophysiology and clinical relevance of platelet heterogeneity[J]. Blood. 1998, 72: 1–8
[16] Martin JF, Trowbridge EA, Salmon G, et al. The biological significance of platelet volume: Its relationship to bleeding time, thromboxane B2 production and megakaryocyte nuclear DNA concentration[J]. Thromb Res. 1983, 32: 443–460.
[17] Sewell R, Ibbotson RM, Philips R. High mean platelet volume after myocardial infarction: Is it due to consumption of small platelets?[J]. Br Med J. 1984, 289: 1576–1580
[18] Zuberi B, Akhtar N, Afsar S. Comparison of mean platelet volume in patients with diabetes mellitus, impaired fasting glucose and non-diabetic subjects[J]. Singapore Med J. 2008, 49(2):114-116
[19] Coban E, Ozdogan M, Yazicioglu G, et al. The mean platelet volume in patients with obesity[J]. Int J Clin Pract. 2005, 59: 981–982
[20] Kong AP, Choi KC, Cockram CS, et al. Independent associations of alanine aminotransferase (ALT) levels with cardiovascular risk factor clustering in Chinese adolescents[J]. J Hepato. 2008, 49: 115–122
[21] Wang CC, Lin SK, Tseng YF, et al. Elevation of serum aminotransferase activityincreases risk of carotid atherosclerosis in patients with non-alcoholic fatty liver disease[J]. J Gastroenterol Hepato. 2009, 24: 1411–1416
[1] Raszeja-Wyszomirska J, Lawniczak M, Marlicz W, et al. Non-alcoholic fatty liver disease--new view[J]. Pol Merkur Lekarski, 2008, 24(144): 568-571.
[2] Keishi K, Susumu T, Tomoji N, et al. Angiotensin II participates in hepatic inflammation and fibrosis through MCP-1 expression[J]. Dig Dis Sci, 2005, 5(50): 942–948.
[3] Yokohama S , Yoneda M, Haneda M, et al.Therapeutic efficacy of an angiotensin II receptor antagonist in patients with nonalcoholic steatohepatitis[J]. J Hepatol, 2004, 40(5): 1222-1225.
[4] Paschos P, Paletas K. Non alcoholic fatty liver disease and metabolic syndrome[J]. Hippokratia, 2009, 13(1): 9–19.
[5] Sudheer K, Mantena A, King K, et al. Mitochondrial dysfunction and oxidative stress in the pathogenesis of alcohol and obesity induced fatty liver diseases[J]. Free Radical Biology and Medicine, 2008, 44(7): 1259-1272.
[6] Cusi K. Role of insulin resistance and lipotoxicity in non-alcoholic steatohepatitis[J]. Clin Liver Dis, 2009, 13(4): 545-563.
[7] Santos R, Ferreira A. Angiotensin-(1-7) and the renin-angiotensin system[J]. Curr Opin Nephrol Hypertens, 2007, 16(2): 122–128.
[8] Herath C, Warner F, Lubel J, et al. Upregulation of hepatic angiotensin-converting enzyme 2 (ACE2) and angiotensin-(1-7) levels in experimental biliary fibrosis[J]. J Hepatol, 2007, 47(3): 387–395.
[9] Nogueira A, Souza S, Simoes E, et al. The pregnancy induced increase of plasma angiotensin -(1-7) is blunted in gestational diabetes[J]. Regul Pept, 2007, 141(1-3): 55–60.
[10] Walkíria W, Ant?nio R, Regina M, et al. Relationship between angiotensin(1-7) and angiot- ensin II correlates with hemodynamic changes in human liver cirrhosis[J]. World J Gastroenterol, 2009 ,15(20): 2512–2519.
[11] Bataller R, Sancho-Bru P, Ginès P, et al. Activated human hepatic stellate cells express the renin-angiotensin system and synthesize angiotensin II[J].Gastroenterology, 2003, 125(1): 117-25.
[12] Yang L, Bataller R, Dulyx J, et al. Attenuated hepatic inflammation and fibrosis in angiotensin type 1a receptor deficient mice[J]. J Hepatol, 2005, 43(2): 317–323.
[13] Hitoshi Y, Ryuichi N, Yasuhide I, et al. Losartan, an angiotensin-II type 1 receptor blocker, attenuates the liver fibrosis development of non-alcoholic steatohepatitis in the rat[J]. BMC Res Notes, 2009, 2: 70.
[14] Shimamoto K, Miura T. Metabolic syndrome[J]. Nippon Rinsho, 2009, 67(4): 771-776.
[15] Weir M. Effects of renin-angiotensin system inhibition on end-organ protection: can we do better?[J]. Clin Ther, 2007, 29(9): 1803-1824.
[16] Jorge E, Marina C, Gabriel C, et al. ACE inhibition and AT1 receptor blockade prevent fatty liver and fibrosis in obese zucker rats[J]. Obesity, 2008, 16(4): 770–776.
[17] Harrihar A, Pershadsingh, David M. PPAR Agonists: Potential as therapeutics for neovascular retinopathies[J]. PPAR Res, 2008, 2008: 164273.
[18] Ziemke F, Mantzoros C. Adiponectin in insulin resistance: lessons from translational rsearch[J]. Am J Clin Nutr, Epub 2009 Nov 11.
[19] Parsons C, Takashima M, Rippe R. Molecular mechanisms of hepatic fibrogenesis[J]. J Gastroenterol Hepatol, 2007, 22 Suppl 1: S79-84.
[20] Kitamura K, Tada S, Nakamoto N, et al. Rho/Rho kinase is a key enzyme system involved in the angiotensin II signaling pathway of liver fibrosis and steatosis[J]. J Gastroenterol Hepatol, 2007, 22(11): 2022-2033.
[21] Bataller R, Sancho-Bru P, Ginès P. Liver Fibrogenesis: A new role for the renin–angiotensin system[J]. Antioxid Redox Signal, 2005, 7(9-10): 1346-1355.
[22] Park D, Baik S, Choi Y, et al. Inhibitory effect of angiotensin blockade on hepatic fibrosis in common bile duct-ligated rats. Korean J Hepatol, 2007, 13(1): 61-69.
[23] Kim M, Baik S, Park D, et al. Angiotensin receptor blockers are superior to angiotensin -converting enzyme inhibitors in the suppression of hepatic fibrosis in a bile duct-ligated rat model[J]. J Gastroenterol, 2008, 43(11): 889-896.
[24] Ramon B, Pau S, Pere G, et al. Liver fibrogenesis: a new role for the renin–angiotensin system[J]. Antioxic Redox Signal, 2005, 7(9-10) : 1346–1355.
[25] Li X, Meng Y, Cai S, et al. Aldosterone stimulates alpha1-(1) procollagen mRNA expression in HSC via activation of ERK1/2 and AP-1[J]. Zhonghua Gan Zang Bing Za Zhi, 2005, 13(11): 815-818.
[26] Osterreicher C, Taura K, De -Minicis S, et al. Angiotensin-converting-enzyme 2 inhibits liver fibrosis in mice[J]. Hepatology, 2009, 50(3): 929-938.
[27] 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: 179-187.
[28] Osterreicher C, Taura K, De -Minicis S, et al. Angiotensin-converting-enzyme 2 inhibits liver fibrosis in mice[J]. Hepatology, 2009, 50(3): 929-938
[29] Pereira R, dos- Santos R, da -Costa D. Renin-angiotensin system in the pathogenesis of liver fibrosis[J]. World J Gastroenterol, 2009, 15(21): 2579-2586.
[30] Lubel J, Herath C, Burrell L, et al. Liver disease and the renin-angiotensin system: recent discoveries and clinical implications[J]. J Gastroenterol Hepatol, 2008, 23(9): 1327-1338.