摘要
Objective To determine whether all-trans retinoic acid (atR A) 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 chromornetry, 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 μg/mg vs 5.10 ± 0.91 μg/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 μg/mg vs 7.96 ± 1.13 μg/mg and 7.77 ± 0.96 μg/mg vs 9.93 ± 1.27μg/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.
目的 探讨全反式维甲酸 (all transretinoicacid ,atRA)对肺动脉高压肺血管重建的干预作用。方法 所有动物分成三组 :对照组、模型组和atRA组。利用野百合碱 (monocrotalineMCT)诱导大鼠肺动脉高压模型 ,同时给予atRA治疗。经导管介入测定平均肺动脉压 ,逆转录半定量聚合酶链反应 (RT PCR)检测不同时间点肺组织MMP 1mRNA相对表达水平 ,比色法测定肺动脉段羟脯氨酸含量。结果 对照组大鼠平均肺动脉压于不同时间无显著性差异 ,而模型组平均肺动脉压于第 2 1天已明显升高 ,并持续升高至实验的第 2 8天。肺组织MMP 1mRNA表达水平的升高以实验第 14天最为明显 ,第 2 1天和 2 8天表达水平下调 ,但仍高于对照组。肺动脉段羟脯氨酸含量第 14天异常降低 ,以后随平均肺动脉压的升高而升高。atRA抑制MMP 1mRNA过度表达 ,抑制作用从 14天直到 2 8天 ,并明显降低第 2 1天和 2 8天肺动脉段羟脯氨酸含量 ,明显降低肺动脉压 ,差异均有显著性。结论 atRA能影响MMP 1mRNA表达和细胞外基质中的胶原含量 ,降低平均肺动脉压 。
