胆道闭锁,胶原三螺旋重复蛋白 1,肝纤维化,胆总管囊肿,调控机制 ," /> 胆道闭锁,胶原三螺旋重复蛋白 1,肝纤维化,胆总管囊肿,调控机制 ,"/> Biliary atresia,Collagen triple helix repeat containing 1,Hepatic fibrosis,Choledochal cyst,Regulatory mechanism ,"/> <div> <span style="font-size:14px;line-height:2;">CTHRC1 在胆道闭锁肝组织及血清中的表达及其与肝纤维化的相关性</span> </div>
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发育医学电子杂志  2026, Vol. 14 Issue (3): 243-249    DOI: 10.3969/j.issn.2095-5340.2026.03.011
  生长发育   论著 |
CTHRC1 在胆道闭锁肝组织及血清中的表达及其与肝纤维化的相关性
张芳芳 王刚  崔明宇 井海燕 张丽娟  李梦迪 王帅 马邦振 张子琛
1. 山东第一医科大学附属省立医院 小儿普外科,山东 济南 250021;2. 山东第一医科大学附属省立医院 病理科,山东 济南 250021
Expression of CTHRC1 in liver tissue and serum of patients with biliary atresia and its correlation with liver fibrosis
Zhang Fangfang , Wang Gang, Cui Mingyu, et al.
1.Department of Pediatric General Surgery, Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China; 2.Department of Pathology, Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China
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摘要 
目的 探究胶原三螺旋重复蛋白 1(collagen triple helix repeat containing 1,CTHRC1)在胆道闭锁(biliary atresia,BA)和胆总管囊肿(choledochal cyst,CC)患儿肝组织及血清中的表达差异,并分析其与 BA 患儿肝纤维化程度的相关性。方法 回顾性纳入 2021 年 1 月至 2024 年6 月于山东第一医科大学附属省立医院小儿普外科行手术治疗的Ⅲ型 BA 患儿(BA 组)及 CC 患儿(CC 组),将 BA 组患儿按照肝纤维化分期(GS 分期)分为轻度组(S1、S2 期)和重度组(S3、S4期),分别获取各组患儿的肝组织石蜡切片及血清。收集各组患儿的手术月龄、术时体质量及术前实验室指标[天冬氨酸氨基转移酶(aspartate aminotransferase,AST)、丙氨酸氨基转移酶(alanineaminotransferase,ALT)、γ- 谷氨酰转肽酶(gamma-glutamyl transferase,GGT)、总胆红素(totalbilirubin,TBil)、直接胆红素(direct bilirubin,DBil)、血小板计数(platelet count,PLT)、天冬氨酸氨基转移酶与血小板计比值指数(aspartate aminotransferase-to-platelet count ratio index,APRI)]。通过免疫组织化学染色(immunohistochemical staining,IHC)法检测肝组织中 CTHRC1的表达情况,并采用 Spearman 法分析其与 BA 患儿肝纤维化程度的相关性。通过酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)法检测血清中 CTHRC1 的表达水平,并采用Spearman 法分析其与 GGT、TBil、APRI 的相关性。统计学方法采用 t 检验、Mann-Whitney U 检验。结果 本研究共获取 20 例 BA 患儿和 7 例 CC 患儿的临床资料及肝组织石蜡切片,其中轻度组13例,重度组7例,行 IHC 染色;另外获取10例BA患儿和8例 CC 患儿的临床资料及血清,行 ELISA 法检测。IHC 染色结果显示,BA 组肝组织中 CTHRC1 评分较 CC 组显著升高(P<0.05),重度组肝组织中 CTHRC1 评分较轻度组显著升高(P<0.05),BA 患儿肝组织中 CTHRC1 评分与肝纤维化程度呈正相关(rs=0.790,P<0.001)。ELISA 法检测结果显示,BA 组血清中 CTHRC1 表达水平高于 CC 组(P<0.05)。结论 BA患儿肝组织及血清中 CTHRC1 表达增强,且在肝组织中的表达程度与肝纤维化程度呈正相关,CTHRC1有望成为BA 辅助诊断的生物学标志物。
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Abstract: Objective To investigate the differences in the expression of collagen triple helix repeat  containing 1 (CTHRC1) in liver tissue and serum of children with biliary atresia (BA) and choledochal cyst (CC), and its correlation with the degree of hepatic fibrosis in children with BA. Methods This study retrospectively enrolled pediatric patients who underwent surgical treatment for BA with type Ⅲ (BA group) and CC (CC group) at the Department of Pediatric General Surgery, Provincial Hospital Affiliated to Shandong First Medical University from January 2021 to June 2024. According to the liver fibrosis stage (GS stage), children in the BA group were divided into the mild group (stage S1, S2) and the severe group (stage
S3, S4). Liver tissue paraffin sections and serum were obtained from each group. Clinical data including age at surgery, body weight at surgery, and preoperative laboratory parameters [aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), total bilirubin (TBil), direct bilirubin (DBil), platelet count (PLT), and aspartate aminotransferase-to-platelet count ratio index (APRI)] were collected. The expression of CTHRC1 in liver tissue was detected by immunohistochemical staining (IHC), and its correlation with the liver fibrosis degree in BA children was analyzed using Spearman method. The expression level of CTHRC1 in serum was detected by enzyme-linked immunosorbent assay (ELISA), and their correlations with GGT, TBil, and APRI were analyzed using Spearman method. Statistical analysis was performed by t-test and Mann-Whitney U test. Results Clinical data and liver tissue paraffin sections were obtained from 20 children with BA and 7 children with CC for IHC detection, including 13 cases in the mild group and 7 cases in the severe group. Additionally, clinical data and serum were obtained from another 10 children with BA and 8 children with CC for ELISA detection. The results of IHC detection showed that the CTHRC1 score in liver tissue of the BA group was significantly higher than that in the CC group (P<0.05), and significantly higher in the severe group than that in the mild group (P<0.05); the CTHRC1 score in liver tissue of children with BA was positively correlated with liver fibrosis degree (rs=0.790, P<0.001). The results of ELISA detection showed that the expression level of CTHRC1 in serum of the BA group was higher than that in the CC group (P<0.05). Conclusion The expression of CTHRC1 in liver tissue and serum of children with BA was enhanced, and the degree of expression in liver tissue was positively correlated with hepatic fibrosis degree, and CTHRC1 is expected to be a biological marker for the auxiliary diagnosis of BA.
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收稿日期:  2025-01-17                出版日期:  2026-05-30      发布日期:  2026-05-30      期的出版日期:  2026-05-30
通讯作者:  王刚    E-mail:  wangg@sdfmu.edu.cn
引用本文:    
张芳芳 王刚 崔明宇 井海燕 张丽娟 李梦迪 王帅 马邦振 张子琛.
CTHRC1 在胆道闭锁肝组织及血清中的表达及其与肝纤维化的相关性
[J]. 发育医学电子杂志, 2026, 14(3): 243-249.
Zhang Fangfang , Wang Gang, Cui Mingyu, et al..
Expression of CTHRC1 in liver tissue and serum of patients with biliary atresia and its correlation with liver fibrosis
. Journal of Developmental Medicine(Electronic Version), 2026, 14(3): 243-249.
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http://www.fyyxzz.com/CN/10.3969/j.issn.2095-5340.2026.03.011  或          http://www.fyyxzz.com/CN/Y2026/V14/I3/243
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