Department of Cardiovascular Diseases, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin 300381, China.
Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
Dis Markers. 2022 Feb 18;2022:3229888. doi: 10.1155/2022/3229888. eCollection 2022.
Pulmonary hypertension (PH) is a chronic and progressive disease caused by obstructions and functional changes of small pulmonary arteries. Current treatment options of PH are costly with patients needing long-term taking medicine. The traditional Chinese medicine (TCM) compound "Shufeiya Recipe" was used to intervene in monocrotaline- (MCT-) induced pulmonary hypertension in rats. The rats were randomly divided into the control group, model group, positive drug (Sildenafil) group, and Shufeiya Recipe low-, moderate-, and high-dose groups. The improvement effect of the Shufeiya Recipe on the mean pulmonary artery pressure (mPAP) was assessed in PH rats, and pathological staining was used to observe the pathological changes of lung tissue. The impact of the Shufeiya Recipe on oxidative stress damage in rats with pulmonary hypertension and the regulation of SIRT3/FOXO3a and its downstream signaling pathways were determined. The results showed that Shufeiya Recipe could significantly downregulate mPAP and improve lung histopathological changes; downregulate serum levels of reactive oxygen species (ROS); upregulate the concentrations of COX-1 and COX-2 and the activity of Mn-SOD; inhibit oxidative response damage; promote the protein expression of SIRT3, FOXO3a, p-PI3K, p-AKT, and p-eNOS; increase the level of expression of NO, sGC, cGMP, and PKG; and downregulate the level of protein expression of Ras, p-MEK1/2, p-ERK1/2 and c-fos. These results indicate that Shufeiya Recipe can improve MCT-induced pulmonary hypertension in rats by regulating SIRT3/FOXO3a and its downstream PI3K/AKT/eNOS and Ras/ERK signaling pathways.
肺动脉高压（PH）是一种由小肺动脉阻塞和功能改变引起的慢性进行性疾病。目前 PH 的治疗选择费用高昂，患者需要长期服药。中药复方“舒心亚方”被用于干预野百合碱（MCT）诱导的大鼠肺动脉高压。将大鼠随机分为对照组、模型组、阳性药物（西地那非）组、舒心亚方低、中、高剂量组。评估舒心亚方对 PH 大鼠平均肺动脉压（mPAP）的改善作用，并进行病理染色观察肺组织的病理变化。确定舒心亚方对肺动脉高压大鼠氧化应激损伤的影响及其对 SIRT3/FOXO3a 及其下游信号通路的调节作用。结果表明，舒心亚方能显著下调 mPAP，改善肺组织病理变化；下调血清活性氧（ROS）水平；上调 COX-1 和 COX-2 浓度及 Mn-SOD 活性；抑制氧化应激损伤；促进 SIRT3、FOXO3a、p-PI3K、p-AKT 和 p-eNOS 蛋白表达；增加 NO、sGC、cGMP 和 PKG 的水平；下调 Ras、p-MEK1/2、p-ERK1/2 和 c-fos 蛋白表达水平。这些结果表明，舒心亚方通过调节 SIRT3/FOXO3a 及其下游的 PI3K/AKT/eNOS 和 Ras/ERK 信号通路，可改善 MCT 诱导的大鼠肺动脉高压。
