非酒精性脂肪性肝病患者血清视黄醛结合蛋白4的变化及临床意义

摘要/Abstract

摘要： 目的观察非酒精性脂肪性肝病(NAFLD)患者视黄醇结合蛋白4(RBP4)的变化及其临床意义。方法收集2016年7月至2018年6月上海市第八人民医院收治的80例NAFLD患者( NAFLD组),另选取健康体检者72例(健康对照组)。80例NAFLD患者中单纯NAFLD患者30例,伴ALT异常的NAFLD患者50例。检测所有研究对象的ALT、AST、TG、TC、FBG、空腹胰岛素水平及RBP4水平,观察NAFLD患者ALT异常、肝纤维化程度、胰岛素抵抗程度与RBP4的相关性。计量资料组间比较采用独立样本t检验,计数资料组间比较采用χ²检验,两变量间的相关性采用Pearson相关系数分析。结果 NAFLD组患者的AST、ALT、TG、TC、FBG、HOMA-IR、NAFLDFS水平均显著高于健康对照组(t值分别为8.016、8.581、4.997、10.080、4.877、6.989、5.639, P值均＜0.01 );RBP4水平显著高于健康对照组[(533.95±197.21) ngl/ml vs (249.09±58.78) ngl/mL,t=11.791,P<0.05]。肝纤维化危险组的FBG、HOMA-IR、RBP4高于无肝纤维化组[FBG:(7.05±2.12)mmol/L vs (5.05±0.33)mmol/L,t=-4.644,P<0.01;HOMA-IR(3.88±1.76)vs(2.36±1.72),t=-4.725,P<0.01;RBP4:(588.23±133.33)ngl/ml vs (463.40±103.20)ngl/mL,t=-4.721,P<0.01]。伴ALT异常NAFLD患者的血清ALT水平显著高于单纯NAFLD患者[ALT:(106.79±59.56) U/L vs (26.90±8.21)U/L,t=-7.081,P<0.01];但RBP4无明显差异[RBP4:(509.80±118.76) ngl/mL vs (520.44±139.93) ngl/mL,t=-0.348,P=0.729]。Pearson相关性分析结果显示,RBP4与HOMA-IR、NAFLDFS呈显著正相关(r值分别为0.430、0.464,P值均＜0.01);与ALT(r=-0.061,P=0.593)无相关。结论 NAFLD患者存在RBP4高表达,且在胰岛素抵抗、肝纤维化程度高的NAFLD患者中表现更为明显。血清RBP4能在一定程度上反映NAFLD患者胰岛素抵抗、肝纤维化的严重程度。

宁惠明, 徐燕华. 非酒精性脂肪性肝病患者血清视黄醛结合蛋白4的变化及临床意义[J]. 肝脏, 2020, 25(4): 429-432.

参考文献

[1] Seo JA, Kim NH, Park SY, et al. Serum retinol-binding protein 4 levels are elevated in nonalcoholic fatty liver disease.Clin Endocrinol( Oxf),2008,68:555-560.
[2] Wu H, Jia W, Bao Y, et al.Serum retinol binding protein 4 and nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus . Diabetes Res Clin Pract, 2008, 79:185-190.
[3] Schina M, Koskinas J, Tiniakos D , et al.Circulating and liver tissue levels of retinol-binding protein4 in nonalcoholic fatty liver disease.Hepatol Res,2009,39:972-978.
[4] Nobili V, Alkhouri N, Alisi A,et al.Retinol-binding protein 4:a promising circulating marker of liver damage in pediatric nonalcoholic fatty liver disease. Gastroenterol Hepatol,2009,7:575-579.
[5] 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疗指南(2018年更新版).实用肝脏病杂志,2018,21:177-186.
[6] Graham TE, Yang Q, Blüher M, et al. Retinol-binding protein 4 and insulin resistance in lean,obese,and diabetic subjects.N Engl J Med,2006,354: 2552-2563.
[7] Blaner WS.Vitamin A signaling and homeostasis in obesity, diabetes,and metabolic disorders.Pharmacol Ther,2019,197:153-178.
[8] Lee SA, Yuen JJ, Jiang H,et al.Adipocyte-specific over-expression of retinol-binding protein 4(RBP4) causes hepatic steatosis in mice.Hepatology,2016,64:1534-546.
[9] Zhong G, Kirkwood J, Won KJ, et al.Characterization of Vitamin A Metabolome in Human Livers With and Without Nonalcoholic Fatty Liver Disease.J Pharmacol Exp Ther, 2019,370:92-103.
[10] Wang X, Chen X, Zhang H, et al.Circulating retinol-binding protein 4 is associated with the development and regression of non-alcoholic fatty liver disease.Diabetes Metab,2019, S1262-3636:30069-30072.
[11] von Eynatten M, Humpert PM.Retinol-binding protein-4 in experimental and clinical metabolic disease.Expert Rev Mol Diagn,2008,8:289-299
[12] Yang Q, Graham TE, Mody N, et al.Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes.Nature,2005,436:356-362.
[13] Kukla M, Ciupińska-Kajor M, Kajor M, et al.Liver visfatin expression in morbidly obese patients with nonalcoholic fatty liver disease undergoing bariatric surgery.Pol J Pathol,2010,61:147-153.
[14] Liu S, Wu HJ, Zhang ZQ, et al.The ameliorating effect of rosiglitazone on experimental nonalcoholic steatohepatitis is associated with regulating adiponectin receptor expression in rats. Eur J Pharmacol,2011,650:384-389.
[15] Zarzour RHA, Alshawsh MA, Asif M, et al. Adipocytokine regulation and antiangiogenic activity underlie the molecular mechanisms of therapeutic effects of phyllanthus niruriagainst non-alcoholic fatty liver disease. Nutrients,2018,10:1057.
[16] Tan Y, Sun LQ, Kamal MA, et al.Suppression of retinol-binding protein 4 with RNA oligonucleotide prevents high-fat diet-induced metabolic syndrome and non-alcoholic fatty liver disease in mice. Biochim.Biophys.Acta Mol.Cell Boil.Lipids,2011,1811: 1045-1053.