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维生素 D 状态及维生素 D 受体和 LL-37 在自发性细菌性腹膜炎患者中的表达。

Vitamin D status and expression of vitamin D receptor and LL-37 in patients with spontaneous bacterial peritonitis.

机构信息

Department of Infectious Diseases, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, China.

出版信息

Dig Dis Sci. 2012 Jan;57(1):182-8. doi: 10.1007/s10620-011-1824-6. Epub 2011 Jul 14.

Abstract

BACKGROUND

Vitamin D, which exerts its effect through vitamin D receptor (VDR), and LL-37, a vitamin D-dependent antimicrobial peptide, are involved in many infectious diseases.

AIM

The objective of this study was to evaluate whether vitamin D status and expressions of VDR and LL-37 are involved in the pathogenesis of spontaneous bacterial peritonitis (SBP).

METHODS

Serum and ascitic fluid 25-dihydroxyvitamin D [25(OH)D] concentrations and levels of VDR and LL-37 in peritoneal leukocytes were measured by ELISA and real-time PCR methods in cirrhotic patients with SBP (n = 19) and cirrhotic patients with simple ascites (n = 28). The correlations between these levels and clinical variables were evaluated.

RESULTS

Cirrhotic patients with ascites showed low vitamin D concentrations in both serum and ascitic fluid. Lower serum vitamin D concentrations were observed in cirrhotic patients with Child-Pugh C class. 25(OH)D concentrations in ascitic fluid were positive correlated with that in serum (r = 0.74, P < 0.001). The SBP group showed significantly higher levels of both VDR and LL-37 mRNA expressions in peritoneal leukocytes than the simple ascites group (P = 0.005 and P = 0.003, respectively). In the SBP group, VDR and LL-37 expressions in peritoneal leukocytes were positively correlated (r = 0.70, P = 0.001).

CONCLUSIONS

Vitamin D insufficiency was universal among cirrhotic patients with ascites, and the situation was more severe with more serious cirrhosis. Expressions of peritoneal leukocytes VDR and LL-37 genes were simultaneously up-regulated in cirrhotic patients with SBP when compared with cirrhotic patients with simple ascites. It is indicated that the vitamin D-VDR system and its downstream gene, LL-37, are involved in the pathogenesis and antibacterial immune response to SBP.

摘要

背景

维生素 D 通过维生素 D 受体 (VDR) 发挥作用,而 LL-37 是一种维生素 D 依赖性抗菌肽,参与多种感染性疾病。

目的

本研究旨在评估维生素 D 状态以及 VDR 和 LL-37 的表达是否与自发性细菌性腹膜炎 (SBP) 的发病机制有关。

方法

通过酶联免疫吸附试验和实时 PCR 方法测量肝硬化伴 SBP 患者 (n = 19) 和肝硬化单纯腹水患者 (n = 28) 血清和腹腔液 25-羟维生素 D [25(OH)D] 浓度以及腹腔白细胞中 VDR 和 LL-37 的水平。评估这些水平与临床变量之间的相关性。

结果

肝硬化腹水患者血清和腹腔液中维生素 D 浓度均较低。Child-Pugh C 级肝硬化患者血清维生素 D 浓度较低。腹腔液中 25(OH)D 浓度与血清中 25(OH)D 浓度呈正相关 (r = 0.74,P < 0.001)。与单纯腹水组相比,SBP 组腹腔白细胞中 VDR 和 LL-37 mRNA 表达水平均显著升高 (P = 0.005 和 P = 0.003)。在 SBP 组中,腹腔白细胞中 VDR 和 LL-37 的表达呈正相关 (r = 0.70,P = 0.001)。

结论

肝硬化伴腹水患者普遍存在维生素 D 不足,且随着肝硬化程度的加重,情况更为严重。与肝硬化单纯腹水患者相比,SBP 患者腹腔白细胞中 VDR 和 LL-37 基因的表达同时上调。这表明维生素 D-VDR 系统及其下游基因 LL-37 参与 SBP 的发病机制和抗细菌免疫反应。

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