The Seventh Inpatient Area, Qingdao Sixth People's Hospital, No. 9, Fushun Road, Shibei District, Qingdao City, Shandong Province, 266033, China.
Department of Inspection, Qingdao Sixth People's Hospital, No. 9, Fushun Road, Shibei District, Qingdao City, Shandong Province, 266033, China.
Pathol Res Pract. 2020 May;216(5):152876. doi: 10.1016/j.prp.2020.152876. Epub 2020 Feb 13.
This research aimed to explore the correlation between miR-34a expression in peripheral blood and clinical characteristics of patients with chronic hepatitis C (CHC) as well as the diagnostic and prognostic values of serum miR-34a in CHC.
Serum samples of 41 CHC patients and 18 normal participants were collected to examine the expression levels of miR-34a using qRT-PCR. The changes of serum TBA, liver enzyme AST and ALT were also determined by enzyme colorimetry and rate method. The levels of serum fibrotic markers hyaluronic acid (HA), type III procollagen (PCIII), type IV collagen (IV-C) and laminin (LN) were detected by radioimmunoassay. Degree of liver fibrosis was examined by liver biopsy. Western blot analysis was used to investigate the expression of ac-p53, p53 and Sirt1 in the liver tissues of CHC patients.
MiR-34a was significantly increased in the serum of CHC patients than that in healthy participants, and serum miR-34a was correlated with liver fibrosis index. Serum TBA, AST and ALT levels, and AST/ALT ratios in patients with CHC were increased with increasing degree of fibrosis, and were positively associated with serum miR-34a. Furthermore, the liver tissues of CHC patients showed low Sirt1 protein expression and highly ac-p53 protein expression.
Serum miR-34a in patients with CHC could promote liver fibrosis through mediating the Sirt1/p53 pathway and might function as pivotal biomarker on the prognosis and diagnosis of CHC patients.
本研究旨在探讨慢性丙型肝炎（CHC）患者外周血 miR-34a 表达与临床特征的相关性，以及血清 miR-34a 在 CHC 中的诊断和预后价值。
收集 41 例 CHC 患者和 18 例正常对照者的血清样本，采用 qRT-PCR 检测 miR-34a 的表达水平。采用酶比色法和速率法检测血清总胆汁酸（TBA）、肝酶天门冬氨酸氨基转移酶（AST）和丙氨酸氨基转移酶（ALT）的变化。采用放射免疫法检测血清纤维化标志物透明质酸（HA）、III 型前胶原（PCIII）、IV 型胶原（IV-C）和层粘连蛋白（LN）的水平。通过肝活检检查肝纤维化程度。采用 Western blot 分析检测 CHC 患者肝组织中 ac-p53、p53 和 Sirt1 的表达。
CHC 患者血清 miR-34a 明显高于健康对照者，血清 miR-34a 与肝纤维化指数相关。CHC 患者血清 TBA、AST 和 ALT 水平及 AST/ALT 比值随纤维化程度的增加而升高，与血清 miR-34a 呈正相关。此外，CHC 患者的肝组织中 Sirt1 蛋白表达降低，ac-p53 蛋白表达升高。
CHC 患者血清 miR-34a 可通过介导 Sirt1/p53 通路促进肝纤维化，可能作为 CHC 患者预后和诊断的重要生物标志物。
