原发性布加综合征患者内皮祖细胞水平及其功能与因子 V 莱顿和蛋白 C 缺乏的关系。

Department of Vascular Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, China.

Eur Rev Med Pharmacol Sci. 2018 May;22(9):2742-2750. doi: 10.26355/eurrev_201805_14971.

OBJECTIVE

Budd-Chiari syndrome (BCS) is a life-threatening hepatic disease characterized by hepatic venous obstruction at the level of hepatic vein, hepatic venules, or inferior vena cava. No evidence reported the relationship between the endothelial progenitor cells and the deficiency of factor V Leiden and protein C in patients with primary Budd-Chiari syndrome.

PATIENTS AND METHODS

We recruited participants between June 2014 and July 2015. For primary BCS group, 28 patients were collected. 20 patients were included in the NAFLD group. Another 73 healthy participants were recruited into the control group. None of the patients and participants had received interventional therapy or had undergone surgery prior to being recruited. Levels and functions of endothelial progenitor cells (EPCs) were examined. The factor V Leiden mutation, protein C deficiency and protein S deficiency were evaluated. Finally, the relationship between the levels and function of endothelial progenitor cells and factor V Leiden and protein C deficiency in patients with primary Budd-Chiari syndrome was analyzed.

RESULTS

The results showed that no significant differences were found between the BCS (and NAFLD) and control group considering age, sex, BMI, smoking (p>0.05 for variables). However, significant differences were observed in TG, TC, HDL-C, white blood cells, hemoglobin, ALT, AST, ALP, γ-GT, total bilirubin, and albumin (p<0.05 for variables). Compared with the healthy participants, significant downregulation was found in BCS and NAFLD patients regarding CD34+/CD45-, late outgrowth endothelial cells (OECs) colonies, OECs proliferation, and OECs tubulogenesis (p<0.001 for variables). Among the 28 BCS patients, factor V Leiden mutation (n=10, 35.71%, OR 12.67, 95% CI 5.24-27.93) and hereditary protein C deficiency (n=4, 14.29%, OR 7.48, 95% CI 2.02-21.43) were more prevalent than those in the control group. These results suggested that factor V Leiden mutation and protein C deficiency were major risk factors for BCS. Finally, we demonstrated that factor V Leiden and protein C deficiency may negatively regulate the OECs levels and functions in BCS patients.

CONCLUSIONS

It's important to improve the OECs levels and functions, and to prevent the deficiency of factor V Leiden and protein C in the treatment of BCS.

目的

布加综合征（BCS）是一种危及生命的肝脏疾病，其特征为肝静脉、肝小静脉或下腔静脉水平的肝静脉阻塞。目前尚无证据表明原发性布加综合征患者内皮祖细胞与因子 V 莱顿和蛋白 C 缺乏之间存在关系。

患者和方法

我们于 2014 年 6 月至 2015 年 7 月期间招募了参与者。对于原发性 BCS 组，共收集了 28 名患者。NAFLD 组纳入了 20 名患者。此外，还招募了 73 名健康参与者作为对照组。所有患者和参与者在入组前均未接受过介入治疗或手术。检测内皮祖细胞（EPCs）的水平和功能。评估因子 V 莱顿突变、蛋白 C 缺乏和蛋白 S 缺乏。最后，分析原发性布加综合征患者内皮祖细胞水平和功能与因子 V 莱顿和蛋白 C 缺乏之间的关系。

结果

结果显示，BCS（和 NAFLD）组与对照组在年龄、性别、BMI、吸烟等方面无显著差异（变量 p>0.05）。然而，在 TG、TC、HDL-C、白细胞、血红蛋白、ALT、AST、ALP、γ-GT、总胆红素和白蛋白方面存在显著差异（变量 p<0.05）。与健康参与者相比，BCS 和 NAFLD 患者的 CD34+/CD45-、晚期成血管内皮细胞（OECs）集落、OECs 增殖和 OECs 管腔形成明显下调（变量 p<0.001）。在 28 名 BCS 患者中，因子 V 莱顿突变（n=10，35.71%，OR 12.67，95%CI 5.24-27.93）和遗传性蛋白 C 缺乏（n=4，14.29%，OR 7.48，95%CI 2.02-21.43）比对照组更常见。这些结果表明因子 V 莱顿突变和蛋白 C 缺乏是 BCS 的主要危险因素。最后，我们证明因子 V 莱顿和蛋白 C 缺乏可能会负调控 BCS 患者的 OECs 水平和功能。