慢性乙型肝炎患者血清miR-29b、miR-30c水平及与肝纤维化的关系

The expressions of serum miR-29b and miR-30c in patients with chronic hepatitis B and their relationships with liver fibrosis

目的探讨慢性乙型肝炎患者血清miR-29b、miR-30c表达及其与肝纤维化的关系,为临床治疗慢性乙型肝炎患者肝纤维化提供新思路。方法收集南京中医药大学附属南京医院2015年9月-2018年6月期间慢性乙型肝炎患者98例,根据肝脏组织病理检查分为轻、中重度肝纤维化组,并选取同期体检健康者47人作为健康对照组。使用qRT-PCR法检测研究对象血清miR-29b、miR-30c表达水平,采用免疫层析法检测肝纤维化指标透明质酸(HA)、Ⅲ型前胶原(PC-Ⅲ)、Ⅳ型胶原(C-IV)、层粘连蛋白(LN),并采用受试者工作曲线(ROC)评估miR-29b、miR-30c对肝纤维化的诊断价值。结果与健康对照组相比,轻度、中重度肝纤维化组miR-29b、miR-30c水平显著降低,HA、PC-Ⅲ、C-Ⅳ、LN水平显著增高,差异均有统计学意义(P<0.05)。与轻度肝纤维化组相比,中重度肝纤维化组miR-29b和miR-30c水平显著降低,HA、PC-Ⅲ、C-Ⅳ、LN水平显著增高,差异均有统计学意义(P<0.05)。Pearson相关性结果表明,miR-29与HA、PC-Ⅲ、C-Ⅳ、LN呈负相关(r=-0.755、-0.684、-0.412、-0.625,P<0.05);miR-30c与HA、PC-Ⅲ、C-Ⅳ、LN呈负相关(r=-0.528、-0.711、-0.678、-0.669,P<0.05)。ROC曲线分析显示miR-29b、miR-30c以及二者联合检测预测慢性乙型肝炎患者发生肝纤维化曲线下面积分别为0.809(敏感度:73.1%,特异性:79.8%)、0.800(敏感度:85.3%,特异性:72.4%)、0.965(敏感度:96.5%,特异性:82.4%)。结论血清miR-29b、miR-30c在肝纤维化患者中低表达,检测血清miR-29b、miR-30c的表达水平对评估慢性乙型肝炎患者是否发生肝纤维化具有重要临床应用价值。

Objective To investigate the expressions of serum miR-29b and miR-30c in patients with chronic hepatitis B and their relationships with liver fibrosis,and provide new ideas for clinical treatment of liver fibrosis in patients with chronic hepatitis B.Methods 98 patients with chronic hepatitis B from September 2015 to June 2018 were collected and divided into mild,moderate and severe hepatic fibrosis groups according to liver histopathological examination,and healthy persons were selected as healthy control group during the same period.The levels of serum miR-29b and miR-30 c were detected by qRT-PCR,hyaluronic acid(HA);typeⅢprocollagen(PC-Ⅲ),typeⅣcollagen(C-Ⅳ),and laminin(LN)were detected by immunochromatography,and the receiver operating curve(ROC)was used to evaluate the diagnostic values of miR-29b and miR-30c in liver fibrosis.Results The levels of serum miR-29 b,miR-30 c,and hepatic fibrosis indicators HA,PC-Ⅲ,C-Ⅳ,and LN in the three groups were significantly different(P<0.05);compared with healthy control group,the levels of miR-29b and miR-30c in mild,moderate and severe hepatic fibrosis groups decreased significantly(P<0.05),while the levels of HA,PC-Ⅲ,C-Ⅳ,and LN increased significantly;compared with mild hepatic fibrosis group,the levels of miR-29b and miR-30c in moderate and severe hepatic fibrosis group decreased significantly(P<0.05),while the levels of HA,PC-Ⅲ,C-Ⅳ,and LN increased significantly.Pearson correlation results showed that miR-29 was negatively correlated with HA,PC-Ⅲ,C-Ⅳ,and LN(r=-0.755,-0.684,-0.412,-0.625,P<0.05);miR-30 c was negatively correlated with HA,PC-Ⅲ,C-Ⅳ,and LN(r=-0.528,-0.711,-0.678,-0.669,P<0.05);ROC curve analysis showed that the area under the miR-29b curve was 0.809,the sensitivity was 73.1%,and the specificity was 79.8%;the area under the miR-30c curve was 0.800,the sensitivity was 85.3%,and the specificity was 72.4%;the area under the two joint detection curve was 0.965,sensitivity was 96.5%,and specificity was 82.4%.Conclusion Serum miR-29b and miR-30c levels were low in patients with liver fibrosis;detection of serum miR-29b and miR-30c levels could evaluate whether hepatic fibrosis occurs in patients with chronic hepatitis B,which has important clinical value.