| 摘要: |
| 目的：观察复方葶苈子汤对慢性阻塞性肺疾病（COPD）相关性肺动脉高压（PAH）大鼠模型氧化应激的影响，探讨其可能的作用机制。方法：采用随机数字表法将50只SD大鼠分为正常组、模型组及中药低、中、高剂量组。除正常组以外，其余各组大鼠均采用烟熏加气管滴注脂多糖构建COPD-PAH模型。造模后第2天开始灌胃干预，每天2次，连续2周，中药低、中、高剂量组灌胃剂量分别为2.50 g/kg、5.00 g/kg、10.00 g/kg，模型组灌胃0.9%氯化钠注射液10 ml/kg。观察大鼠的一般情况；测量大鼠的肺功能、平均肺动脉压力（mPAP）；HE染色观察其肺组织肺血管病理形态变化；检测大鼠血清中超氧化物歧化酶（SOD）活力值、环磷酸腺苷（MDA）含量、cAMP含量，肺组织中泛素连接酶2（Siah2）mRNA的相对表达量；检测肺组织细胞中Siah2、A激酶锚定蛋白（Akap121）的蛋白表达水平。结果：与模型组比较，中药各剂量组肺血管损伤重构减轻，mPAP下降（P<0.05）；大鼠血清中SOD活力值、MDA含量、cAMP含量、Siah2-RNA相对表达量，正常组与模型组、模型组与中药各剂量组比较，差异均有统计学意义（P<0.05）。与模型组比较，中药各剂量组肺组织Siah2蛋白表达降低，AKAP-121蛋白表达上调，差异均有统计学意义（P<0.05）。结论：复方葶苈子汤可通过调控cAMP-Siah2-AKAP121通路来减少氧化应激对COPD-PAH大鼠的肺血管壁的损伤，降低肺动脉压。 |
| 关键词: 慢性阻塞性肺疾病 肺动脉高压 复方葶苈子汤 氧化应激 |
| DOI： |
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| Mechanism of action of compound Semen Lepidii decoction in reducing pulmonary artery pressure in rats with chronic obstructive pulmonary disease-related pulmonary arterial hypertension：A study based on oxidative stress |
| ZHU Junmi,WU Xincheng,LIU Min |
| (Hunan University of Chinese Medicine，Changsha 410208，Hunan，China;Hunan Academy of Chinese Medicine，Changsha 410006，Hunan，China) |
| Abstract: |
| Objective：To investigate the effect of compound Semen Lepidii decoction on oxidative stress in a rat model of chronic obstructive pulmonary disease (COPD)-related pulmonary arterial hypertension (PAH) and its possible mechanism of action.Methods：A total of 50 Sprague-Dawley rats were divided into normal group，model group，and low-，middle-，high-dose traditional Chinese medicine (TCM) groups using a random number table.All rats except those in the normal group were given smudging and intratracheal instillation of lipopolysaccharide to establish a model of COPD-PAH.Intragastric administration was started on day 2 after modeling，twice a day for 2 consecutive weeks，at a dose of 2.50 g/kg for the low-dose group，5.00 g/kg for the middle-dose group，and 10.00 g/kg for the high-dose group，and the rats in the model group were given 0.9% sodium chloride injection by gavage at a dose of 10 ml/kg.The general status of rats was observed；pulmonary function and mean pulmonary artery pressure (mPAP) were measured；HE staining was used to observe the pathomorphological changes of lung tissue and vessels；the activity of superoxide dismutase (SOD) in serum was measured，as well as the content of malondialdehyde (MDA) and cyclic adenosine monophosphate (cAMP) in serum and the relative mRNA expression level of the ubiquitin ligase seven-in-absentia homolog 2 (Siah2) in lung tissue；the protein expression levels of Siah2 and A-kinase anchor protein (AKAP121) in lung tissue were also measured.Results：Compared with the model group，all TCM groups had alleviation of pulmonary vascular injury and remodeling and a significant reduction in mPAP (P<0.05)，and there were significant differences in SOD activity，MDA content，cAMP content，and the relative mRNA expression level of Siah2 between the normal group and the model group and between the model group and the TCM groups (P<0.05).Compared with the model group，the TCM groups had a significant reduction in the protein expression level of Siah2 and a significant increase in the protein expression level of AKAP121 in lung tissue (P<0.05).Conclusion：Compound Semen Lepidii decoction can alleviate the injury of pulmonary vascular wall due to oxidative stress and reduce pulmonary artery pressure in COPD-PAH rats by regulating the cAMP-Siah2-AKAP121 pathway. |
| Key words: chronic obstructive pulmonary disease pulmonary hypertension compound Semen Lepidii decoction oxidative stress |
