| 摘要: |
| [摘要]目的：探讨Rho激酶抑制剂法舒地尔对低氧性肺动脉高压（HPH）大鼠内皮素-1（ET-1）和一氧化氮（NO）表达的影响。方法：将24只雄性SD大鼠随机分为对照组、模型组和法舒地尔干预组各8只。对照组常氧下饲养，每天与模型组同一时间腹腔注射等量生理盐水；模型组每天低氧前腹腔注射生理盐水2 mL/kg；法舒地尔干预组每天低氧前腹腔注射法舒地尔15 mg/kg，用生理盐水稀释成2 mL/kg给药。模型组和法舒地尔干预组采用常压间断低氧法建立大鼠HPH模型，低氧浓度为10%±0.5%，每天低氧8 h，每周低氧6 d，共21 d。测定各组大鼠平均肺动脉压力（mPAP）、右心室肥厚指数（RVHI）；应用放射免疫法和硝酸还原酶法分别测定血浆ET-1和NO水平；光镜下观察大鼠肺血管形态结构。结果：模型组的mPAP、RVHI、ET-1均高于法舒地尔干预组和对照组，而NO水平低于法舒地尔干预组和对照组（P均<0.01）。模型组大鼠的mPAP、RVHI与血浆ET-1水平呈正相关，与血浆NO水平呈负相关；血浆ET-1与NO呈负相关（P均<0.01）。模型组大鼠肺小动脉管壁普遍增厚，管腔明显狭窄，法舒地尔干预组肺小动脉管壁增厚程度及管腔狭窄程度显著减轻。结论：法舒地尔能显著降低HPH大鼠血浆ET-l水平和上调NO水平，阻抑肺动脉高压的发展。 |
| 关键词: 低氧性肺动脉高压 法舒地尔 内皮素-1 一氧化氮 |
| DOI：doi:10.13407/j.cnki.jpp.1672-108X.2018.04.001 |
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| 基金项目: |
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| Effect of Fasudil on Expression of Endothelin-1 and Nitric Oxide in Rats with Hypoxic Pulmonary Hypertension |
| Sun Xingzhen1, Hong Ze1, Li Jiaxin1, Zhang Rongrong1, Chen Xueying2 |
| (1. Huai’an First People’s Hospital AffiIiated to Nanjing Medical University, Jiangsu Huai’an 223300, China; 2. Nanjing ChiIdren's Hospital AffiIiated to Nanjing MedicaI University, Jiangsu Nanjing 210008, China) |
| Abstract: |
| [Abstract] Objective: To investigate the effect of Rho kinase inhibitor fasudil on expression of endothelin-1 (ET-1) and nitric oxide
(NO) in rats with hypoxic pulmonary hypertension( HPH). Methods: Twenty-four SD male rats were randomly divided into control
group, hypoxic model group and fasudil-intervention group. The control group was raised under the normal oxygen condition, and the
equal amount of normal saline was injected into both the control group and the hypoxic model group. 2 mL/kg of the normal saline was
injected into the hypoxic model before the low oxygen condition every day. 15 mL/kg of the normal saline was injected into the fasudil-
intervention group with the normal saline diluted into 2 mL/kg. The rat model of HPH was established by exposing rats to normobaric
intermittent hypoxic conditions, with the low oxygen density of 10.0%±0.5% for 8 hours per day, 6 days per week and 21 days in total.
The mean pulmonary arterial pressure (mPAP) and right ventricle hypertrophy index (RVHI) were measured. The levels of plasma ET-1
and NO were detected by radioimmunoassay and nitrate reductase method respectively. The pulmonary vessels morphologic changes in
the three groups were studied with light microscope. Results: The levels of mPAP, RVHI and ET-1 were significantly higher in the
hypoxic model group than those in the control group and fasudil-intervention group, the level of plasma NO in the model group was lower
than the control group and fasudil-intervention group ( all P<0.01) . In model group, plasma ET-1 concentration was significantly
positively related to mPAP and RVHI, whereas NO concentration was negatively related to the levels of mPAP and RVHI (all P<0.01).
Plasma ET-1 concentration was significantly negatively correlated with the level of NO (P<0.01). Under light microscopy, pulmonary
artery wall thickening and luminal stenosis were significantly ameliorated in fasudil-intervention group. Conclusion: Fasudil can
significantly reduce the level of plasma ET-1 in HPH rats and increase the NO level, and prevent pulmonary hypertension development. |
| Key words: hypoxic pulmonary hypertension fasudil endothelin-1 nitric oxide |
