全反式维甲酸在野百合碱诱导的大鼠肺动脉高压肺血管结构重塑中的作用

All-trans retinoic acid in pulmonary vascular structural remodeling in rats with pulmonary hypertension induced by monocrotaline.

作者信息

Qin Y, Zhou A, Ben X, Shen J, Liang Y, Li F

机构信息

Shanghai Institute for Pediatric Medical Research, Xinhua Hospital, Shanghai Second Medical University, Shanghai 200092, China.

出版信息

Chin Med J (Engl). 2001 May;114(5):462-5.

PMID:11780404

Abstract

OBJECTIVE

To determine whether all-trans retinoic acid (atRA) exerts an inhibitory effect on rats with pulmonary hypertension induced by monocrotaline.

METHODS

All rats were given a single subcutaneous injection of either monocrotaline (60 mg/kg) or saline. Monocrotaline-injected rats received either atRA (30 mg.kg-1.day-1) or saline through oral-gastro intubation. On Days 7, 14, 21, and 28 respectively after monocrotaline injection, cardiovascular catheters were inserted to examine the mean pulmonary artery pressure of rats in each group. Meanwhile, the matrix metalloproteinase-1 (MMP-1) mRNA expression and hydroxyproline content in the main pulmonary artery were determined by RT-PCR and chromometry, respectively.

RESULTS

The mean pulmonary artery pressure of rats in the model group increased significantly on day 21 and reached a peak on Day 28 compared with the control group (25.7 +/- 4.3 mm Hg vs 15.1 +/- 1.5 mm Hg and 38.5 +/- 6.4 mm Hg vs 16.4 +/- 2.0 mm Hg, P < 0.01). MMP-1 mRNA overexpression was present on Day 14 (0.72 +/- 0.15 vs 0.39 +/- 0.08, P < 0.01) and was rapidly down-regulated on Day 21 and 28 compared with Day 14, but was still higher than that in the control. The hydroxyoroline content of the main pulmonary artery dropped significantly on Day 14 (4.01 +/- 1.13 micrograms/mg vs 5.10 +/- 0.91 micrograms/mg, P < 0.05) and increased significantly on Days 21 and 28 compared with the control. atRA inhibited the MMP-1 mRNA overexpression from Day 14 to Day 28 and reduced the hydroxyproline content (5.59 +/- 0.70 micrograms/mg vs 7.96 +/- 1.13 micrograms/mg and 7.77 +/- 0.96 micrograms/mg vs 9.93 +/- 1.27 micrograms/mg, P < 0.01) and the mean pulmonary artery pressure compared with the model group (19.6 +/- 3.2 mm Hg vs 25.7 +/- 4.3 mm Hg and 26.3 +/- 4.6 mm Hg vs 38.5 +/- 6.4 mm Hg, P < 0.01).

CONCLUSION

atRA inhibits MMP-1 overexpression and the accumulation of collagen, which might elicit favorable geometric remodeling in rat pulmonary hypertension induced by monocrotaline.

摘要

目的

确定全反式维甲酸（atRA）对野百合碱诱导的大鼠肺动脉高压是否具有抑制作用。

方法

所有大鼠均皮下注射一次野百合碱（60mg/kg）或生理盐水。注射野百合碱的大鼠通过经口胃插管给予atRA（30mg·kg-1·天-1）或生理盐水。在注射野百合碱后的第7、14、21和28天，分别插入心血管导管以检测每组大鼠的平均肺动脉压。同时，分别通过逆转录聚合酶链反应（RT-PCR）和比色法测定主肺动脉中基质金属蛋白酶-1（MMP-1）mRNA表达和羟脯氨酸含量。

结果

与对照组相比，模型组大鼠的平均肺动脉压在第21天显著升高，并在第28天达到峰值（25.7±4.3mmHg对15.1±1.5mmHg以及38.5±6.4mmHg对16.4±2.0mmHg，P<0.01）。MMP-1 mRNA在第14天出现过表达（0.72±0.15对0.39±0.08，P<0.01），与第14天相比，在第21天和28天迅速下调，但仍高于对照组。主肺动脉的羟脯氨酸含量在第14天显著下降（4.01±1.13μg/mg对5.10±0.91μg/mg，P<0.05），与对照组相比，在第21天和28天显著增加。与模型组相比，atRA从第14天至第28天抑制MMP-1 mRNA过表达，降低羟脯氨酸含量（5.59±0.70μg/mg对7.96±1.13μg/mg以及7.77±0.96μg/mg对9.93±1.27μg/mg，P<0.01）以及平均肺动脉压（19.6±3.2mmHg对25.7±4.3mmHg以及26.3±4.6mmHg对38.5±6.4mmHg，P<0.01）。