非酒精性脂肪性肝病儿童血清人尾肢同源蛋白水平检测的临床意义

Clinical significance of serum Pygo2 expression in children with NAFLD

目的目前仍不了解非酒精性脂肪性肝病(NAFLD)患儿人尾肢同源蛋白(Pygo2)血清水平在疾病进展过程中作用,以及可否评估肝纤维化程度。文中旨在检测肥胖儿童外周血中的Pygo2水平,并分析其与传统肝纤维化血清学指标之间的关系,从而评估NAFLD患儿Pygo2检测的实际临床价值。方法选择2014年9月至2016年2月在安徽医科大学附属省立医院和南京医科大学第一附属医院就诊的住院和门诊肥胖患儿120例。参考NAFLD诊疗指南将120例肥胖患儿分为单纯性肥胖组(n=44例,肝B超无弥漫性脂肪肝的肥胖儿童)、单纯性非酒精性脂肪肝(NAFL)组(n=35例,肝B超提示有弥漫性脂肪肝但肝功能正常)、非酒精性脂肪肝炎(NASH)组(n=41例,肝B超提示有弥漫性脂肪肝且肝功能异常)。另选取18例健康志愿者为对照组。对照组及所有患者均收集外周血清,并分别采用酶联免疫吸附方法测定血清Pygo2水平,放射免疫分析法检测透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(CⅣ)和层粘连蛋白(LN)和全自动酶法测定血清丙氨酸氨基转移酶(ALT)和γ-谷氨酰转肽酶(γ-GT)表达量。结果 NAFL组、NASH组Pygo2表达量[52.1(12.3)、78.3(50.0)μg/L]较单纯性肥胖组[43.2(18.7)μg/L]明显升高(P<0.05);NASH组Pygo2表达量较对照组[41.7(16.8)μg/L]、NAFL组明显升高(P<0.001)。NAFH组HA、CⅣ、LN、ALT、γ-GT表达量较对照组、单纯性肥胖组、NAFL组明显升高(P<0.001)。血清Pygo2与HA、PCⅢ、CⅣ、ALT、γ-GT、LN呈显著正相关(r=0.708、0.356、0.589、0.454、0.674,0.169,P<0.05)。结论随着Pygo2表达量水平升高,肝纤维化程度加重。Pygo2与HA、CⅣ、γ-GT等指标显著相关,表明Pygo2亦可作为检测NAFLD患儿肝纤维化的临床评估指标。

Objective The role of serum Pygo2 expression in children with non-alcoholic fatty liver disease（ NAFLD） in the disease process and whether it can be used to evaluate the degree of liver fibrosis still remain unknown. The article aimed to detect Pygo2 expression in the peripheral blood of children with NAFLD and analyze its relationship with traditional serum hepatic fibrosis index in order to evaluate the clinical significance of Pygo2 measurement in children with NAFLD. Methods We enrolled 120 cases of childhood obesity and 18 healthy controls in Anhui Provincial Hospital and the First Affiliated Hospital of Nanjing Medical University from September 2014 to February 2016. The cases of childhood obesity were divided into simple obesity group（ n = 44,no diffuse fatty liver under liver ultrasound detection）,NAFL group（ n = 35,diffuse fatty liver with normal liver function under liver ultrasound detection） and NASH group（ n = 41,diffuse fatty liver with abnormal liver function under liver ultrasound detection）. The peripheral serum was collected from all patients and healthy controls. ELISA was used to detect serum Pygo2 expression and radioimmunoassay was used to detect the serum hyaluronia acid（ HA）,procollagen type Ⅲ（ PCⅢ）,procollagen type Ⅳ（ CⅣ） and laminin（ LN） levels. Finally the serum ALT and γ-GT levels were measured with totally automatic enzymatic method. Results Pygo2 expression in NAFL group [52.1（ 12.3） μg/L] and NASH group[78.3（ 50.0） μg/L] increased significantly compared with simple obesity group [43. 2（ 18. 7） μg/L]（ P〈0.05）. Pygo2 expression in NASH group increased significantly compared with control group [41.7（ 16.8） μg/L] and NAFL group（ P〈0.001）. The serum hepatic fribrosis and inflammation markers（ HA,PC,ALT,C III and IV gamma-GT） levels gradually increased in the obese children. There were statistically positive correlations between serum Pygo2 and HA,PCⅢ,CⅣ,ALT or γ-GT（ P〈0.001）. In particular,more significant positive correlations were found between serum Pygo2 and HA,CⅣ or γ-GT（ r = 0.708,P〈0.001; r = 0.589,P〈0.001; r = 0.674,P〈0.05）. Conclusion The degree of liver fibrosis worsens with the increase of Pygo2 expression and Pygo2 is in remarkable correlation with conventional hepatic fibrosis serum makers（ HA,C IV） or γ-GT,which shows Pygo2 expression can be taken as the clinical evaluation index of liver fibrosis in children with NAFLD.