非酒精性脂肪性肝病儿童血清25-(OH)D3和IL-17水平变化初步研究
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摘要
目的调查非酒精性脂肪性肝病(NAFLD)肥胖儿童血清25羟维生素D3[血清25-(OH)D3]和白介素-17(IL-17)水平变化。方法 2014年1月～2017年12月我院诊治的肥胖儿童62例,参照非酒精性脂肪性肝病诊疗指南标准诊断单纯性非酒精性脂肪肝(NAFL)36例,非酒精性脂肪性肝炎(NASH)26例,另选健康儿童30例,采用ELISA法检测血清25-(OH)D和IL-17水平。结果 NAFL儿童血清25-(OH)D3水平为(15.2±2.1) ng/mL,NASH儿童为(9.6±1.3) ng/ml,均显著低于健康儿童的(26.3±2.3) ng/mL,而血清IL-17水平分别为(17.1±7.8)μg/L和(36.2±12.6)μg/L,均显著高于健康儿童的(1.4±0.5)μg/L,差异均有统计学意义(P<0.05);中度脂肪变儿童血清ALT和AST水平分别为(54.1±15.4) U/L和(46.5±12.6) U/L,重度组儿童分别为(117.1±37.1) U/L和(78.5±31.0) U/L,均显著高于轻度组的(33.4±4.6) U/L和(30.5±2.9) U/L(P<0.05);中度脂肪变儿童血清25-(OH)D3水平为(10.2±1.4) ng/ml,重度组儿童为(8.4±1.1) ng/ml,显著低于轻度组的(15.8±2.0) ng/mL(P<0.05),而血清IL-7水平分别为(22.2±6.3)μg/L和(39.6±9.2)μg/L,显著高于轻度脂肪变儿童的(13.5±3.5)μg/L,组间差异均有显著性统计学意义(P<0.05)。结论 NAFLD儿童血清25-(OH)D3水平降低,而血清IL-17水平升高,它们的变化可能与肝内脂肪变程度有关,动态监测这些变化,可能对了解病情和防治效果判断起指导作用。
Objective To investigate serum 25-(OH)D_3 and interleukin-17(IL-17) levels in obese children with nonalcoholic fatty liver disease(NAFLD). Methods Sixty-two obese children were enrolled in this study between January 2014 and December 2017,and out of them,36 cases were diagnosed as nonalcoholic fatty liver(NAFL) and 26 were nonalcoholic steatohepatitis(NASH). Thirty healthy children were selected as control.Serum IL-17 and 25-(OH)D_3 levels were assayed by ELISA. Results Serum 25-(OH)D_3 level in children with NAFL was(15.2±2.1) ng/mL,and in children with NASH was(9.6±1.3) ng/ml,both significantly lower than(26.3±2.3) ng/mL in healthy children,while serum IL-17 levels were(17.1±7.8) μg/L and(36.2±12.6) μg/L,both significantly higher than(1.4±0.5) μg/L in healthy children(P<0.05);serum ALT and AST levels in children with moderate NAFLD were(54.1±15.4) U/L and(46.5±12.6) U/L,and were(117.1±37.1) U/L and(78.5±31.0) U/L in children with severe NAFLD,all significantly higher than(33.4±4.6) U/L and(30.5±2.9) U/L in kids with mild NAFLD(P<0.05);serum 25-(OH)D_3 level in children with moderate NAFLD was(10.2±1.4) ng/ml and in children with severe NAFLD was(8.4 ±1.1) ng/ml,both significantly lower than(15.8 ±2.0) ng/ml in children with mild NAFLD(P<0.05),while serum IL-7 levels were(22.2±6.3)μg/L and(39.6±9.2) μg/L,respectively,significantly higher than(13.5±3.5) μg/L in children with mild NAFLD(P<0.05). Conclusion Serum 25-(OH)D_3 levels decrease and serum IL-17 levels increase in obese children with NAFLD,which might be new indicators for supervision of disease progress.
Objective To investigate serum 25-(OH)D_3 and interleukin-17(IL-17) levels in obese children with nonalcoholic fatty liver disease(NAFLD). Methods Sixty-two obese children were enrolled in this study between January 2014 and December 2017,and out of them,36 cases were diagnosed as nonalcoholic fatty liver(NAFL) and 26 were nonalcoholic steatohepatitis(NASH). Thirty healthy children were selected as control.Serum IL-17 and 25-(OH)D_3 levels were assayed by ELISA. Results Serum 25-(OH)D_3 level in children with NAFL was(15.2±2.1) ng/mL,and in children with NASH was(9.6±1.3) ng/ml,both significantly lower than(26.3±2.3) ng/mL in healthy children,while serum IL-17 levels were(17.1±7.8) μg/L and(36.2±12.6) μg/L,both significantly higher than(1.4±0.5) μg/L in healthy children(P<0.05);serum ALT and AST levels in children with moderate NAFLD were(54.1±15.4) U/L and(46.5±12.6) U/L,and were(117.1±37.1) U/L and(78.5±31.0) U/L in children with severe NAFLD,all significantly higher than(33.4±4.6) U/L and(30.5±2.9) U/L in kids with mild NAFLD(P<0.05);serum 25-(OH)D_3 level in children with moderate NAFLD was(10.2±1.4) ng/ml and in children with severe NAFLD was(8.4 ±1.1) ng/ml,both significantly lower than(15.8 ±2.0) ng/ml in children with mild NAFLD(P<0.05),while serum IL-7 levels were(22.2±6.3)μg/L and(39.6±9.2) μg/L,respectively,significantly higher than(13.5±3.5) μg/L in children with mild NAFLD(P<0.05). Conclusion Serum 25-(OH)D_3 levels decrease and serum IL-17 levels increase in obese children with NAFLD,which might be new indicators for supervision of disease progress.
引文
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[11]中华医学会肝病学分会脂肪肝和酒精性肝病学组,中国医师协会脂肪肝专家委员会.非酒精性脂肪性肝病防治指南(2018年版).实用肝脏病杂志,2018,21(2):177-186.
[12]Altinbas A,Sowa J P,Hasenberg T,et al.The diagnosis and treatment of non-alcoholic fatty liver disease.Minerva Gastroenterol Dietol,2015,61(3):159-169.
[13]王存川,张艺超.肥胖症与代谢疾病外科治疗的发展.中华消化外科杂志,2015,14(7):524-527.
[14]Ogden CL,Carroll MD,Kit BK,et al.Prevalence of childhood and adult obesity in the United States,2011-2012.JAMA,2014,311(8):806.
[15]王红清,付映旭,徐佩茹,等.25羟维生素D水平与儿童肥胖关系的Meta分析.中华临床医师杂志(电子版),2015,9(10):125-128.
[16]张红霞,原杰,贺业新,等.太原社区非糖尿病人群血清维生素D与腹型肥胖的相关性.中华临床营养杂志,2015,23(4):219-223.
[17]Ferro M,Terracciano D,Buonerba C,et al.The emerging role of obesity,diet and lipid metabolism in prostate cancer.Future Oncol,2016,34(2):285-293.
[18]Su DL,Lu ZM,Shen MN,et al.Roles of pro-and anti-inflammatory cytokines in the pathogenesis of SLE.J Biomed Biotechnol,2012,2012(4):347141.
[19]Dobritsa SV,Kuok IT,Nguyen H,et al.Development of a highthroughput cell-based assay for identification of IL-17 inhibitors.J Biomol Screen,2013,18(1):75-84.
[20]Carla H,Chackelevicius N,Sabrina LG,et al.Th17 involvement in nonalcoholic fatty liver disease progression to non-alcoholic steatohepatitis.World J Gastroenterol,2016,22(41):9096-9103.
[21]Fawaz L,Mrad MF,Kazan JM,et al.Comparative effect of 25(OH)D3and 1,25(OH)2D3on Th17 cell differentiation.Clin Immunol,2016,166-167:59-71.
[22]Webster GF,Webster TG,Grimes LR.Laboratory tests in patients treated with isotretinoin:occurrence of liver and muscle abnormalities and failure of AST and ALT to predict liver abnormality.Dermatol Online J,2016,23(5):103.
[23]Drori A,Rotnemergolinkin D,Avni S,et al.Attenuating the rate of total body fat accumulation and alleviating liver damage by oral administration of vitamin d-enriched edible mushrooms in a diet-induced obesity murine model is mediated by an anti-inflammatory paradigm shift.Bmc Gastroenterol,2017,17(1):130.
[24]Hakkak R,Gauss C,Bell A,et al.Short-term soy protein isolate feeding prevents liver steatosis and reduces serum ALT and AST levels in obese female Zucker rats.Biomedicines,2018,6(2):74-78.
[25]Karpyak V,Biernacka J,Geske J,et al.Genome-wide association analyses reveal snp-by-consumption interaction effects on ALT And AST levels in alcohol dependent patients.Eur Neuropsychopharmacol,2017,27(5):S412.
[2]赵泽华,范建高.2016年美国肝病年会非酒精性脂肪性肝病深度报道.实用肝脏病杂志,2017,20(1):21-24.
[3]Jiao N,Baker SS,Chapa-Rodriguez A,et al.Suppressed hepatic bile acid signalling despite elevated production of primary and secondary bile acids in NAFLD.Gut,2017,152(5):S1068.
[4]Doycheva I,Cui J,Nguyen P,et al.Non-invasive screening of diabetics in primary care for NAFLD and advanced fibrosis by MRI and MRE.Aliment Pharmacol Ther,2016,43(1):83-95.
[5]Eduardo F,Francisco F,Gemma V,et al.Mechanisms of chronic state of inflammation as mediators that link obese adipose tissue and metabolic syndrome.Mediators Inflamm,2013,2013(3):136584.
[6]Chehimi M,Vidal H,Eljaafari A.Pathogenic role of IL-17-producing immune cells in obesity,and related inflammatory diseases.J Clin Med,2017,6(7):68.
[7]Ali KR,Kapur P,Jain A,et al.Effect of orlistat on periostin,adiponectin,inflammatory markers and ultrasound grades of fatty liver in obese NAFLD patients.Ther Clin Risk Manag,2017,13:139.
[8]Clemente-Postigo M,Munoz-Garach A,Serrano M,et al.Serum25-hydroxyvitamin D and adipose tissue vitamin D receptor gene expression:relationship with obesity and type 2 diabetes.J Clin Endocrinol Metab,2015,100(4):591-595.
[9]Wu L,Ong S,Talor MV,et al.Cardiac fibroblasts mediate IL-17A-driven inflammatory dilated cardi omyopathy.J Exp Med,2014,211(7):1449-1464.
[10]Hatting M,Tacke F.From NAFLD to HCC:is IL-17 the crucial link Hepatology,2016,65(2):739.
[11]中华医学会肝病学分会脂肪肝和酒精性肝病学组,中国医师协会脂肪肝专家委员会.非酒精性脂肪性肝病防治指南(2018年版).实用肝脏病杂志,2018,21(2):177-186.
[12]Altinbas A,Sowa J P,Hasenberg T,et al.The diagnosis and treatment of non-alcoholic fatty liver disease.Minerva Gastroenterol Dietol,2015,61(3):159-169.
[13]王存川,张艺超.肥胖症与代谢疾病外科治疗的发展.中华消化外科杂志,2015,14(7):524-527.
[14]Ogden CL,Carroll MD,Kit BK,et al.Prevalence of childhood and adult obesity in the United States,2011-2012.JAMA,2014,311(8):806.
[15]王红清,付映旭,徐佩茹,等.25羟维生素D水平与儿童肥胖关系的Meta分析.中华临床医师杂志(电子版),2015,9(10):125-128.
[16]张红霞,原杰,贺业新,等.太原社区非糖尿病人群血清维生素D与腹型肥胖的相关性.中华临床营养杂志,2015,23(4):219-223.
[17]Ferro M,Terracciano D,Buonerba C,et al.The emerging role of obesity,diet and lipid metabolism in prostate cancer.Future Oncol,2016,34(2):285-293.
[18]Su DL,Lu ZM,Shen MN,et al.Roles of pro-and anti-inflammatory cytokines in the pathogenesis of SLE.J Biomed Biotechnol,2012,2012(4):347141.
[19]Dobritsa SV,Kuok IT,Nguyen H,et al.Development of a highthroughput cell-based assay for identification of IL-17 inhibitors.J Biomol Screen,2013,18(1):75-84.
[20]Carla H,Chackelevicius N,Sabrina LG,et al.Th17 involvement in nonalcoholic fatty liver disease progression to non-alcoholic steatohepatitis.World J Gastroenterol,2016,22(41):9096-9103.
[21]Fawaz L,Mrad MF,Kazan JM,et al.Comparative effect of 25(OH)D3and 1,25(OH)2D3on Th17 cell differentiation.Clin Immunol,2016,166-167:59-71.
[22]Webster GF,Webster TG,Grimes LR.Laboratory tests in patients treated with isotretinoin:occurrence of liver and muscle abnormalities and failure of AST and ALT to predict liver abnormality.Dermatol Online J,2016,23(5):103.
[23]Drori A,Rotnemergolinkin D,Avni S,et al.Attenuating the rate of total body fat accumulation and alleviating liver damage by oral administration of vitamin d-enriched edible mushrooms in a diet-induced obesity murine model is mediated by an anti-inflammatory paradigm shift.Bmc Gastroenterol,2017,17(1):130.
[24]Hakkak R,Gauss C,Bell A,et al.Short-term soy protein isolate feeding prevents liver steatosis and reduces serum ALT and AST levels in obese female Zucker rats.Biomedicines,2018,6(2):74-78.
[25]Karpyak V,Biernacka J,Geske J,et al.Genome-wide association analyses reveal snp-by-consumption interaction effects on ALT And AST levels in alcohol dependent patients.Eur Neuropsychopharmacol,2017,27(5):S412.