[肝细胞生长因子早期治疗通过调节细胞因子表达改善肺动脉高压大鼠的肺动脉和右心室重塑]

[Early treatment with hepatocyte growth factor improves pulmonary artery and right ventricular remodeling in rats with pulmonary artery hypertension by modulating cytokines expression].

作者信息

Wang Xiaolin, Wang Yongjin, Rong Shuling, Ma Hongbiao

机构信息

Department of Paediatrics Heping Hospital, Changzhi Medical College, Changzhi, Shanxi 046000, China.

Email:

出版信息

Zhonghua Jie He He Hu Xi Za Zhi. 2014 Jun;37(6):427-32.

PMID:25200042

Abstract

OBJECTIVE

To investigate the effect of early treatment with hepatocyte growth factor (HGF) on the cytokine expression and pulmonary artery, right ventricular (RV) remodeling in the rat model of pulmonary artery hypertension (PAH).

METHODS

The rat model of PAH was produced by injecting monocrotaline, and the model rats were randomly divided into empty adenovirus transfection group (MCT group, n = 10) and HGF gene transfection group(HGF group, n = 10). Another group of rats served as the Sham operation group (Sham group n = 10). After 4 weeks of HGF gene transfection, the histological sections of the lungs and right ventricular (RV) were stained with hematoxylin-eosin (HE) and the pulmonary artery and RV remodeling were examined. The rat lung sections were also immunostained with antibodies against factor VIII, and the capillary density were calculated. Meanwhile, the mRNA expression of TNF-α, IL-6, IL-1β and TGF-β1 in pulmonary arteries and RV were detected by RT-PCR.

RESULTS

HGF gene treatment significantly decreased the ratio of vessel wall thickness to pulmonary artery diameter and the ratio of vessel wall area to total area, and increased the capillary density of lung in PAH rats. HGF gene treatment also significantly decreased cross-sectional area of cardiomyocytes and collagen deposited in RV. Moreover, HGF gene treatment significantly decreased the expression of cytokines in pulmonary artery (TNF-α: 0.82 ± 0.07 vs 0.49 ± 0.09, IL-6: 1.13 ± 0.19 vs 0.68 ± 0.09, IL-1β: 0.86 ± 0.11 vs 0.51 ± 0.07, TGF-β1: 1.18 ± 0.12 vs 0.59 ± 0.10) and RV (TNF-α: 0.79 ± 0.11 vs 0.48 ± 0.08, IL-6: 1.03 ± 0.11 vs 0.63 ± 0.09, IL-1β: 0.81 ± 0.11 vs 0.52 ± 0.07, TGF-β1: 0.94 ± 0.12 vs 0.53 ± 0.10) in MCT induced PAH rats (P < 0.05) .

CONCLUSION

Early treatment with HGF improves pulmonary artery and RV remodeling, possibly by decreasing the expression of TNF-α, IL-6, IL-1β and TGF-β1 in pulmonary arteries and RV.

摘要

目的

探讨肝细胞生长因子（HGF）早期治疗对肺动脉高压（PAH）大鼠模型细胞因子表达及肺动脉、右心室（RV）重塑的影响。

方法

通过注射野百合碱制备PAH大鼠模型，将模型大鼠随机分为空腺病毒转染组（MCT组，n = 10）和HGF基因转染组（HGF组，n = 10）。另一组大鼠作为假手术组（假手术组，n = 10）。HGF基因转染4周后，取肺和右心室（RV）组织切片进行苏木精-伊红（HE）染色，观察肺动脉和RV重塑情况。大鼠肺组织切片还用抗因子VIII抗体进行免疫染色，计算毛细血管密度。同时，采用逆转录-聚合酶链反应（RT-PCR）检测肺动脉和RV中肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）和转化生长因子-β1（TGF-β1）的mRNA表达。

结果

HGF基因治疗显著降低了PAH大鼠的血管壁厚度与肺动脉直径之比以及血管壁面积与总面积之比，并增加了肺毛细血管密度。HGF基因治疗还显著降低了右心室心肌细胞横截面积和胶原沉积。此外，HGF基因治疗显著降低了MCT诱导的PAH大鼠肺动脉（TNF-α：0.82±0.07 vs 0.49±0.09，IL-6：1.13±0.19 vs 0.68±0.09，IL-1β：0.86±0.11 vs 0.51±0.07，TGF-β1：1.18±0.12 vs 0.59±0.10）和右心室（TNF-α：0.79±0.11 vs 0.48±0.08，IL-6：1.03±0.11 vs 0.63±0.09，IL-1β：0.81±0.11 vs 0.52±0.07，TGF-β1：0.94±0.12 vs 0.53±0.10）中细胞因子的表达（P < 0.05）。