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- 2018
血管紧张素转换酶抑制剂/血管紧张素受体拮抗剂对非酒精性脂肪性肝病的疗效及作用机制
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Abstract:
摘要 目的 研究血管紧张素转换酶抑制剂/血管紧张素受体拮抗剂(ACEIs/ARBs)对于非酒精性脂肪性肝病的疗效及作用机制.方法 从新旧RAS系统、胰岛素抵抗、氧化应激、脂肪细胞因子等方面研究了非酒精性脂肪性肝病的发病机制及ACEIs/ARBs的治疗效果和作用机制.结果 ACELs/ARBs可通过调节脂肪细胞因子、抑制炎症因子的释放和肝星状细胞的激活等途径改善患者的胰岛素抵抗、脂质沉积、肝脏炎症及纤维化.结论 通过对NAFLD的发病机制及ACEI或ARB可能的作用途径的研究,给NAFLD的治疗提供了一个新的方向和理论依据.
[1] | BYRNE C D, TARGHER G.NAFLD: a multisystem disease[J]. J Hepatol. 2015, 62(1):S47-S64. |
[2] | YOUNOSSI Z M, KOENIG A B, ABDELATIF D, et al.Global epidemiology of nonalcoholic fatty liver disease—Meta-analytic assessment of prevalence, incidence, and outcomes[J]. Hepatology, 2016, 64(1):73. |
[3] | WARAICH R S, WEIGERT C, KALBACHER H, et al. Phosphorylation of ser357 of rat insulin receptor substrate-1 mediates adverse effects of protein kinase c-on insulin action in skeletal muscle cells[J]. Journal of Biological Chemistry, 2008, 4(25); 283(17):11226-11233. |
[4] | PASCHOS P, TZIOMALOS K.Nonalcoholic fatty liver disease and the renin-angiotensin system: Implications for treatment[J]. World J Hepatol, 2012, 4(12):327. |
[5] | CHU K Y, LEUNG P S.Angiotensin II in type 2 diabetes mellitus[J]. Current Protein & Peptide Science, 2009, 10(1):75-84. |
[6] | INUKAI K,NAKASHIMA Y,WATANABE M,et al.Regulation of adiponectin receptor gene expression in diabetic mice[J]. Am J Physiol Endocrinol Metab, 2005, 288(5):E876. |
[7] | LI, C.ZOU ,N.ZHANG X,et al.Angiotensin-(1-7) as means to improve nonalcoholic steatohepatitis.J Dig Dis.2014;15(93): 1751-2972. |
[8] | SONG H, SHOJIMA N,SAKODA H,et al.Resistin is regulated by C/EBPs, PPARs, and signal-transducing molecules[J]. Biochem Biophys Res Commun, 2002, 299(2):291. |
[9] | SANCHEZSOLANA B,LABORDA J,BALADRON V.Mouse resistin modulates adipogenesis and glucose uptake in 3T3-L1 preadipocytes through the ROR1 receptor[J]. Mol Endocrinol, 2012, 26(1):110-127. |
[10] | ZHOU L,YU X, MENG Q,et al.Resistin reduces mitochondria and induces hepatic steatosis in mice by the protein kinase C/protein kinase G/p65/PPAR gamma coactivator 1 alpha pathway[J]. Hepatology, 2013, 57(4):1384-1393. |
[11] | BERTOLANI C,SANCHOBRU P,FAILLI P,et al.Resistin as an intrahepatic cytokine: overexpression during chronic injury and induction of proinflammatory actions in hepatic stellate cells[J]. Am J Pathol, 2006, 169(6):2042-2053. |
[12] | DONG ZX,SU L,BRYMORA J,et al.Resistin mediates the hepatic stellate cell phenotype[J]. World J Gastroenterol, 2013, 19(28):4475-4485. |
[13] | GALIC S,SACHITHANANDAN N,KAY T W,et al.Suppressor of cytokine signalling (SOCS) proteins as guardians of inflammatory responses critical for regulating insulin sensitivity[J]. Biochemical Journal, 2014, 461(2):177-88. |
[14] | RUI L,YUAN M,FRANTZ D,et al.SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2[J]. J Biol Chem, 2002, 277(44):42394-42398. |
[15] | 李迎新, 洪郁芝. SOCS-3在胰岛素抵抗中的作用机制及研究进展[J]. 中国现代医生, 2016, 54(36):163-168. |
[16] | LI Y X, HONG Y Z.The mechanism and research progress of SOCS3 in insulin resistance[J].Chinese modern doctor, 2016, 54(36):163-168. |
[17] | YU J H, KIM K H, KIM H.SOCS 3 and PPAR-gamma ligands inhibit the expression of IL-6 and TGF-beta1 by regulating JAK2/STAT3 signaling in pancreas[J]. Int J Biochem Cell Biol, 2008, 40(4):677-688. |
[18] | HANDY JA,SAXENA N K,FU P,et al.Adiponectin activation of AMPK disrupts leptin-mediated hepatic fibrosis via suppressors of cytokine signaling (SOCS-3)[J]. J Cell Biochem, 2011, 112(2):1195-1207. |
[19] | SONG B, JIN H,YU X,et al.Angiotensin-converting enzyme 2 attenuates oxidative stress and VSMC proliferation via the JAK2/STAT3/SOCS3 and profilin-1/MAPK signaling pathways[J]. Regulatory Peptides, 2013, 185(16):44. |
[20] | lSHII S,lIZUKA K,MILLER B C,et al.Carbohydrate response element binding protein direcdy promotes lipogenic enzyme gene transcription[J].Proc Natl Acad Sci U S A,2004,101(44):15597. |
[21] | KAKINO S,OHKI T,NAKAYAMA H,et al.Pivotal Role of TNF-a in the Development and Progression of Nonalcoholic Fatty Liver Disease in a Murine Model[J]. Horm Metab Res, 2018,50(1):80-87. |
[22] | PEREIRA R M, SANTOS R A S D,TEIXEIRA M M, et al.The renin-angiotensin system in a rat model of hepatic fibrosis: Evidence for a protective role of Angiotensin-(1-7)[J]. J Hepatol, 2007, 46(4):674-681. |
[23] | HERATH C B, MAK K, BURRELL L M, et al.Angiotensin-(1-7) reduces the perfusion pressure response to angiotensin II and methoxamine via an endothelial nitric oxide-mediated pathway in cirrhotic rat liver[J]. American Journal of Physiology Gastrointestinal & Liver Physiology, 2013, 304(1):G99. |
[24] | HUANG M L, LI X, MENG Y, et al.Upregulation of angiotensin-converting enzyme (ACE) 2 in hepatic fibrosis by ACE inhibitors[J]. Clin Exp Pharmacol Physiol, 2010, 37(1):e1. |
[25] | CHEN Z, YU R, XIONG Y, et al.A vicious circle between insulin resistance and inflammation in nonalcoholic fatty liver disease[J]. Lipids Health Dis, 2017, 16(1):203. |
[26] | OLIVARES-REYES J A, ARELLANO-PLANCARTE A, CASTILLO-HERNANDEZ J R. Angiotensin II and the development of insulin resistance: implications for diabetes[J]. Mol Cell Endocrinol, 2009, 302(2):128-139. |
[27] | DRAZNIN B.Molecular mechanisms of insulin resistance: serine phosphorylation of insulin receptor substrate-1 and increased expression of p85alpha: the two sides of a coin[J]. Diabetes, 2006, 55(8):2392-2397. |
[28] | HIRATANI K, HARUTA T, TANI A J, et al.Roles of mTOR and JNK in serine phosphorylation, translocation, and degradation of IRS-1[J]. Biochemical & Biophysical Research Communications, 2005, 335(3):836-842. |
[29] | XUE B, KIM Y B, LEE A, et al.Protein-tyrosine phosphatase 1B deficiency reduces insulin resistance and the diabetic phenotype in mice with polygenic insulin resistance[J]. Journal of Biological Chemistry, 2007, 282(33):23829-23840. |
[30] | GAUTHERON J, VUCUR M, REISINGER F, et al.A positive feedback loop between RIP3 and JNK controls non-alcoholic steatohepatitis[J]. EMBO Mol Med, 2014, 6(8):1062. |
[31] | CAO X, YANG F Y, XIN Z, et al.The ACE2/Ang-(1-7)/Mas axis can inhibit hepatic insulin resistance[J]. Mol Cell Endocrinol, 2014, 393(1/2):30-38. |
[32] | ICHIOKA M, SSGANAMI T, TSUDA N, et al.Increased expression of macrophage-inducible C-type lectin in adipose tissue of obese mice and humans[J]. Diabetes, 2011, 60(3):819-826. |
[33] | FERDER L, INSERRA F, MARTINEZ-MALDONADO M.Inflammation and the metabolic syndrome: Role of angiotensin II and oxidative stress[J]. Curr Hypertens Rep, 2006, 8(3):191-198. |
[34] | PANERA N,DELLA CC,CRUDELE A, et al.Recent advances in understanding the role of adipocytokines during non-alcoholic fatty liver disease pathogenesis and their link with hepatokines[J]. Expert Rev Gastroenterol Hepatol, 2016, 10(3):393. |
[35] | LARSEN TM,TOUBRO S,ASTRUP A.PPARgamma agonists in the treatment of type II diabetes: is increased fatness commensurate with long-term efficacy?[J]. Int J Obes Relat Metab Disord, 2003, 27(2):147. |
[36] | GIANI J F, MAYER M A, MUNOZ M C, et al.Chronic infusion of angiotensin-(1-7) improves insulin resistance and hypertension induced by a high-fructose diet in rats[J]. Am J Physiol Endocrinol Metab, 2009, 296(2):E262. |
[37] | IWAI M,KANNO H,SENBA I,et al.Irbesartan increased PPARγ activity in vivo in white adipose tissue of atherosclerotic mice and improved adipose tissue dysfunction[J]. Biochemical & Biophysical Research Communications, 2011, 406(1):123-126. |
[38] | HANDY J A,FU P P,KUMAR P,et al.Adiponectin inhibits leptin signalling via multiple mechanisms to exert protective effects against hepatic fibrosis[J]. Biochem J, 2011, 440(3):385-395. |
[39] | ZHANG Q,WANG Y,LIU Y,et al.Effects of telmisartan on resistin expression in a rat model of nonalcoholic steatohepatitis and insulin resistance[J]. Zhonghua Gan Zang Bing Za Zhi, 2015, 23(4):281-285. |
[40] | 张自力, 赵士峰, 许文萱,等. 细胞因子信号转导抑制分子-3在肝纤维化中的作用及研究进展[J]. 中国药理学通报, 2015(12):1646-1651. |
[41] | ZHANG Z L, ZHAO S F, XU W X,et al.Role and progress of cytokines signal transduction inhibitor-3 in liver fibrosis[J]. Chinese Pharmacological Bulletin, 2015(12):1646-1651. |
[42] | FASSHAUER M,PASCHKE R.Regulation of adipocytokines and insulin resistance[J]. Diabetologia, 2003, 46(12):1594-1603. |
[43] | HUANG S,CZECH M P.The GLUT4 glucose transporter[J]. Cell Metabolism, 2007, 5(4):237. |
[44] | SCHENK S,SABERI M,OLEFSKY J M.Insulin sensitivity: modulation by nutrients and inflammation[J]. Journal of Clinical Investigation, 2008, 118(9):2992. |
[45] | DOU L,WANG S, SUN L,et al.Mir-338-3p Mediates Tnf-A-Induced Hepatic Insulin Resistance by Targeting PP4r1 to Regulate PP4 Expression[J]. Cell Physiol Biochem, 2017, 41(6):2419. |
[46] | PRATAP A,SINGH S,MUNDRA V,et al.Attenuation of early liver fibrosis by pharmacological inhibition of smoothened receptor signaling[J]. J Drug Target,2012, 20(9/10/11/12): 770-782. |
[47] | ZHANG X Q,XU C F,YU C H, et al.Role of endoplasmic reticulum stress in the pathogenesis of nonalcoholic fatty liver disease[J]. World J Gastroenterol, 2014, 20(7):1768. |
[48] | 李军, 罗良平, 张洁. 城市社区中老年人群非酒精性脂肪肝与糖尿病、冠心病患病的现况[J]. 暨南大学学报(自然科学与医学版), 2014, 35(3):310-314. |
[49] | LI J, LUO L P, ZHANG J.Prevalence of non-alcoholic fatty liver disease, diabetes, and coronary heart disease in middle-aged and elderly people in urban communities[J]. Journal of Jinan University(Natural Science & Medicine Edition), 2014, 35(3):310-314. |
[50] | FERNANDEZALVAREZ A,ALVAREZ M S,GONZALEZ R,et al.Human SREBP1c expression in liver is directly regulated by peroxisome proliferator-activated receptor alpha (PPARalpha)[J]. Journal of Biological Chemistry, 2011, 286(24):21466-21477. |
[51] | 姬霞. 替米沙坦对NAFLD大鼠肝脏及大网膜脂肪组织中PPARγ表达的影响[D]. 石家庄:河北医科大学, 2012. |
[52] | JI X.Effect of telmisartan on the expression of PPARγ in liver and omental adipose tissue of NAFLD rats[D]. Shijiazhuang: Hebei Medical University, 2012. |
[53] | SHARMA A M, STAELS B.Review: Peroxisome proliferator-activated receptor gamma and adipose tissue--understanding obesity-related changes in regulation of lipid and glucose metabolism[J]. J Clin Endocrinol Metab, 2007, 92(2):386-395. |
[54] | GAO Y, LI Z, GABRIELSEN J S,et al.Adipocyte iron regulates leptin and food intake[J]. J Clin Invest, 2015, 125(9):3681. |
[55] | CHATTERJEE S,GANINI D,TOKAR E J,et al.Leptin is key to peroxynitrite-mediated oxidative stress and Kupffer cell activation in experimental nonalcoholic steatohepatitis[J]. J Hepatol, 2013,58(4): 778-784. |
[56] | UEKI K,FRUMAN D A,BRACHMANN S M,et al.Molecular balance between the regulatory and catalytic subunits of phosphoinositide 3-kinase regulates cell signaling and survival[J]. Molecular & Cellular Biology, 2002, 22(3):965. |
[57] | MAUVAIS-JARVIS F,UEKI K,FRUMAN D A,et al.Reduced expression of the murine p85alpha subunit of phosphoinositide 3-kinase improves insulin signaling and ameliorates diabetes[J]. Journal of Clinical Investigation, 2002, 109(1):141-149. |
[58] | 徐丹, 黄晓东, 张姮,等. 瘦素和瘦素受体及其下游信号通路在非酒精性脂肪性肝病中的表达及临床意义研究[J]. 中国全科医学, 2013, 15(35):4126-4130. |
[59] | XU D, HUANG X D, ZHANG H,et al.Expression and clinical significance of leptin and leptin receptors and their downstream signaling pathways in nonalcoholic fatty liver disease[J]. Chinese Journal of General Surgery, 2013, 15(35): 4126-4130. |
[60] | POLYZOS SA,KOUNTOURAS J,MANTZOROS CS.Leptin in nonalcoholic fatty liver disease: a narrative review[J].Metabolism, 2015, 64(1):60. |
[61] | IKEJIMA K,TAKEI Y,HONDA H,et al.Leptin receptor-mediated signaling regulates hepatic fibrogenesis and remodeling of extracellular matrix in the rat[J]. Gastroenterology, 2002, 122(5):1399. |
[62] | POLYZOS S A,KOUNTOURAS J,MANTZOROS C S.Leptin in nonalcoholic fatty liver disease: a narrative review[J]. Metabolis, 2015, 64(1):60-78. |
[63] | ALAM S,KABIR J,MUSTAFA G,et al.Effect of telmisartan on histological activity and fibrosis of non-alcoholic steatohepatitis: A 1-year randomized control trial[J]. Saudi Journal of Gastroenterology Official Journal of the Saudi Gastroenterology Association, 2016, 22(1):69-76. |
[64] | ZHANG Q Z,LIU Y L,WANG Y R,et al.Effects of telmisartan on improving leptin resistance and inhibiting hepatic fibrosis in rats with non-alcoholic fatty liver disease[J]. Exp Ther Med, 2017, 14(3):2689. |
[65] | 曹倩颖. 替米沙坦对非酒精性脂肪肝大鼠大网膜脂肪组织瘦素分泌及肝组织瘦素受体表达的影响[D]. 石家庄:河北医科大学, 2013. |
[66] | CAO Q Y.Effects of telmisartan on leptin secretion and hepatic leptin receptor expression in omental adipose tissue in rats with non-alcoholic fatty liver[D]. Shijiazhuang: Hebei Medical University, 2013. |
[67] | ESMAILI S,XU A,GEORGE J.The multifaceted and controversial immunometabolic actions of adiponectin[J]. Trends Endocrinol Metab, 2014, 25(9):444. |
[68] | HOSSAIN M M,MUKHEEM A,KAMARUL T.The prevention and treatment of hypoadiponectinemia-associated human diseases by up-regulation of plasma adiponectin[J]. Life Sci, 2015, 135(18):55-67. |
[69] | POLYZOS S A, KOUNTOURAS J,ZAVOS C H.The multi-hit process and the antagonistic roles of tumor necrosis factor-alpha and adiponectin in non alcoholic fatty liver disease[J]. Hippokratia, 2009, 13(2):127. |
[70] | HOWARD J K,FLIER J S.Attenuation of leptin and insulin signaling by SOCS proteins[J].Trends in Endocrinology & Metabolism Tem, 2006, 17(9):365-371. |