L-精氨酸对左向右分流所致肺动脉高压中肺动脉胶原代谢的调节作用。

The modulating effect of L-arginine on collagen metabolism of pulmonary artery in pulmonary hypertension induced by a left-to-right shunt.

作者信息

Wei Bing, Du Junbao, Li Jian, Qi Jianguang, Tang Chaoshu

机构信息

Department of Pediatrics, First Hospital, Peking University, Beijing 100034, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2002 Sep 25;82(18):1273-5.

PMID:12425810

Abstract

OBJECTIVE

To explore the modulating effect of L-arginine on collagen metabolism of pulmonary artery in rats with high pulmonary blood flow-induced pulmonary hypertension and its molecular mechanism.

METHOD

Eighteen rats were randomly divided into 3 groups of 6 rats: shunt group (pulmonary hypertension was established with an abdominal aorta and inferior vena cava shunting), shunt + L-Arg group (L-arginine, 1 g x kg(-1) x d(-1) was given into the stomachs of rats for weeks after shunting), and control group. After 11 weeks of experiment, the pulmonary hemodynamics were studied, the contents of collagen I and collagen III expressions were detected by immunohistochemical assay. The expressions of procollagen I mRNA, procollagen III mRNA, TIMP-1 mRNA and MMP-1 mRNA were detected by in situ hybridization.

RESULTS

After 11 weeks of experiment, the mean pulmonary artery pressure (MPAP) in shunt group was 23.0 mm Hg +/- 0.9 mm Hg, higher than that in shunt + L-Arg group (18.0 mm Hg +/- 1.8 mm Hg, P < 0.01) and that in control group (15.7 mm Hg +/- 1.1 mm Hg, P < 0.01). The expressing integral scores of collagen I and collagen III, the expression of procollagen I mRNA, Procollagen III mRNA, TIMP-1 mRNA, MMP-1 mRNA and the ratio of TIMP-1/MMP-1 were significantly higher in the shunt group than in the other 2 groups (P < 0.01 or P < 0.05).

CONCLUSION

L-arginine reduces the synthesis of extracellular matrix-collagen and increases its degradation. Thus L-arginine has important modulating effects on pulmonary hypertension and pulmonary vascular remodeling induced by high pulmonary blood flow.

摘要

目的

探讨L-精氨酸对高肺血流性肺动脉高压大鼠肺动脉胶原代谢的调节作用及其分子机制。

方法

将18只大鼠随机分为3组，每组6只：分流组（采用腹主动脉与下腔静脉分流法建立肺动脉高压模型）、分流+L-精氨酸组（分流术后数周，给予大鼠灌胃L-精氨酸，1 g·kg⁻¹·d⁻¹）和对照组。实验11周后，研究肺血流动力学，采用免疫组织化学法检测Ⅰ型和Ⅲ型胶原表达量。采用原位杂交法检测Ⅰ型前胶原mRNA、Ⅲ型前胶原mRNA、金属蛋白酶组织抑制因子-1（TIMP-1）mRNA和基质金属蛋白酶-1（MMP-1）mRNA的表达。

结果

实验11周后，分流组平均肺动脉压（MPAP）为23.0 mmHg±0.9 mmHg，高于分流+L-精氨酸组（18.0 mmHg±1.8 mmHg，P<0.01）和对照组（15.7 mmHg±1.1 mmHg，P<0.01）。分流组Ⅰ型和Ⅲ型胶原表达积分、Ⅰ型前胶原mRNA、Ⅲ型前胶原mRNA、TIMP-1 mRNA、MMP-1 mRNA表达及TIMP-1/MMP-1比值均显著高于其他两组（P<0.01或P<0.05）。