血清miR-33a-5p、Sirt6对胆汁淤积症婴幼儿肝纤维化的评估价值

摘要/Abstract

摘要： 目的探讨血清微小核糖核酸-33a-5p(miR-33a-5p)、沉默信息调节因子6(Sirt6)在胆汁淤积症婴幼儿肝纤维化中的评估价值。方法纳入2021年1月—2023年4月期间郑州大学附属儿童医院治疗的105例胆汁淤积症婴幼儿为研究对象(观察组),评估婴幼儿肝组织纤维化程度并分为轻度组41例和中重度组64例;选取在本院常规检查的健康婴幼儿108例作为对照组。采用实时荧光定量PCR(qRT-PCR)法检测血清miR-33a-5p水平,采用酶联免疫吸附法检测血清Sirt6及肝纤四项透明质酸(HA)、层黏连蛋白(LN)、Ⅳ型胶原(Ⅳ-C)、Ⅲ型前胶原(PC-Ⅲ)水平;采用Pearson相关性分析胆汁淤积症婴幼儿血清miR-33a-5p、Sirt6水平与肝纤维化指标的相关性;采用多因素logistic回归分析筛选胆汁淤积症婴幼儿肝纤维化程度加重的影响因素;采用受试者工作特征曲线(ROC曲线)分析血清miR-33a-5p、Sirt6水平对胆汁淤积症婴幼儿肝纤维化的评估价值。结果观察组婴幼儿血清miR-33a-5p为2.04±0.38、HA(218.95±49.47)ng/mL、LN(130.46±31.05)ng/mL、Ⅳ-C(147.36±40.51)ng/mL、PC-Ⅲ(547.18±92.75)ng/mL,高于对照组的1.01±0.24、(80.14±16.31)ng/mL、(17.64±4.98)ng/mL、(75.16±12.94)ng/mL、(140.43±38.22)ng/mL(P<0.05);血清Sirt6为(6.59±1.42)pg/mL,低于对照组的(13.84±3.12)pg/mL(P<0.05)。胆汁淤积症婴幼儿血清miR-33a-5p与HA、LN、Ⅳ-C、PC-Ⅲ均呈正相关(r=0.524、0.508、0.496、0.501,P<0.05),Sirt6与HA、LN、Ⅳ-C、PC-Ⅲ均呈负相关(r=-0.497、-0.516、-0.529、-0.514,P<0.05)。中重度组婴幼儿血清miR-33a-5p、HA、LN、Ⅳ-C、PC-Ⅲ水平高于轻度组,血清Sirt6水平低于轻度组(P<0.05)。miR-33a-5p是胆汁淤积症婴幼儿肝纤维化程度加重的独立危险因素(OR=2.948,P<0.05),Sirt6是胆汁淤积症婴幼儿肝纤维化程度加重的保护因素(OR=0.795,P<0.05)。血清miR-33a-5p、Sirt6水平单独及联合评估胆汁淤积症婴幼儿肝纤维化的AUC分别为0.787、0.825、0.907。结论血清miR-33a-5p、Sirt6水平联合对胆汁淤积症婴幼儿肝纤维化具有较高的评估价值。

关键词: 胆汁淤积症, 婴幼儿, 肝纤维化, 微小核糖核酸-33a-5p, 沉默信息调节因子6

Abstract: Objective To explore the evaluation value of serum microribonucleic acid 33a-5p (miR-33a-5p) and silent information regulatory factor 6 (Sirt6) in liver fibrosis in infants with cholestasis.Methods A total of 105 infants with cholestasis treated in our hospital from January 2021 to April 2023 were included as the study subjects (observation group). The degree of liver tissue fibrosis in infants was evaluated and grouped into a mild group of 41 cases and a moderate to severe group of 64 cases; 108 healthy infants who underwent routine examinations in our hospital were collected as the control group. Real-time fluorescence quantitative PCR (qRT-PCR) method was applied to detect serum miR-33a-5p level, enzyme-linked immunosorbent assay was applied to detect serum Sirt6 and four indicators: hyaluronic acid (HA), laminin (LN), type IV collagen (Ⅳ-C), and type III procollagen (PC-Ⅲ) levels in liver fibrosis; Pearson correlation analysis was applied to analyze the correlation between serum miR-33a-5p, Sirt6 levels and liver fibrosis indicators in infants with cholestasis; multivariate logistic regression analysis? was applied to analyze and screen the influencing factors of worsening liver fibrosis in infants with cholestasis; receiver operating characteristic curve (ROC curve) was applied to analyze the evaluation value of serum miR-33a-5p and Sirt6 levels for liver fibrosis in infants with cholestasis.Results The serum levels of miR-33a-5p (2.04±0.38), HA (218.95±49.47) ng/mL, LN (130.46±31.05) ng/mL, Ⅳ-C (147.36±40.51) ng/mL, PC-Ⅲ (547.18±92.75) ng/mL in the observation group were higher than those in the control group (1.01±0.24), (80.14±16.31) ng/mL, (17.64±4.98) ng/mL, (75.16±12.94) ng/mL, (140.43±38.22) ng/mL (P<0.05), while the serum Sirt6 (6.59±1.42) pg/mL level was lower than that in the control group (13.84±3.12) pg/mL (P<0.05). The serum miR-33a-5p level in infants with cholestasis was positively correlated with HA, LN, Ⅳ-C, and PC-Ⅲ (r=0.524, 0.508, 0.496, 0.501, P<0.05), while Sirt6 level was negatively correlated with HA, LN, Ⅳ-C, and PC-Ⅲ (r=-0.497, -0.516, -0.529, -0.514, P<0.05). The serum levels of miR-33a-5p, HA, LN, Ⅳ-C, PC-Ⅲ in infants in the moderate to severe group were higher than those in the mild group, while the serum Sirt6 level was lower than that in the mild group (P<0.05). MiR-33a-5p was identified as an independent risk factor for the worsening of liver fibrosis in infants with cholestasis (OR=2.948, P<0.05), Sirt6 was a protective factor for the worsening of liver fibrosis in infants with cholestasis (OR=0.795, P<0.05). The AUC of serum miR-33a-5p, Sirt6 levels and their combination for evaluating liver fibrosis in infants with cholestasis was 0.787, 0.825, and 0.907, respectively.Conclusion The combination of serum miR-33a-5p and Sirt6 levels showed high evaluation value for liver fibrosis in infants with cholestasis.

Key words: Cholestasis, Infants, Liver fibrosis, MiR-33a-5p, Silent information regulatory 6

常栋喆, 耿宪杰, 周良, 杨子久. 血清miR-33a-5p、Sirt6对胆汁淤积症婴幼儿肝纤维化的评估价值[J]. 肝脏, 2025, 30(3): 385-390.

CHANG Dong-zhe, GENG Xian-jie, ZHOU Liang, YANG Zi-jiu. Evaluation value of serum miR-33a-5p and Sirt6 in liver fibrosis in infants with cholestasis[J]. Chinese Hepatolgy, 2025, 30(3): 385-390.

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