Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, 563000, China; Department of Pharmacology, Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou, 563000, China.
Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, 563000, China; Department of Pharmacology, Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou, 563000, China.
Biomed Pharmacother. 2021 Jan;133:111081. doi: 10.1016/j.biopha.2020.111081. Epub 2020 Dec 15.
A growing evidence demonstrates that inflammation is a major contributor to the pathogenesis of pulmonary arterial hypertension (PAH). However, blocking inflammation has only been shown to be of minor clinical benefit due to a lack of understanding of the precise inflammation present in PAH. Thus, the present study aimed to investigate characteristics of inflammatory process in PAH induced by monocrotaline (MCT) in rats.
Adult male Sprague-Dawley rats received a single dose of MCT (50 mg/kg, ip), and the occurrence of PAH and inflammation biomarkers were measured at 3, 6, 9, 12, 15, 18, 21, 24, 27 and 30 days after MCT injection.
From the 6th day after the injection of MCT, the mean pulmonary artery pressure gradually increased and doubled on the 30th day, accompanied by right ventricular hypertrophy and pulmonary arterial remodeling in a time-dependent manner. In the first 6 days after MCT treatment, only pro-inflammatory cytokines TNF-α, IL-1β increased, which was defined as acute inflammatory phase, after that, both pro-inflammatory factors TNF-α, IL-1β, IL-6, IL-12 and anti-inflammatory factors Arg1, IL-10, TGF-β increased, which was defined as chronic inflammatory phase. The M1/M2 macrophage ratios in lung and alveolar lavage fluid were elevated on the 6th and 30th day, moreover, which were higher on the 6th than 30th day, and the PI3K/Akt signaling pathway increased along with the progression of PAH and correlated with pro-inflammatory proteins, which revealed also to some extent the characteristics of inflammation of PAH induced by MCT.
The course of PAH induced by MCT injection is progressive with persistent inflammation, which is defined as acute inflammatory phase within 6 days after MCT treatment, after that, is defined as chronic inflammatory phase.
越来越多的证据表明炎症是肺动脉高压（PAH）发病机制的主要因素。然而，由于缺乏对 PAH 中存在的确切炎症的理解，阻断炎症仅显示出较小的临床益处。因此，本研究旨在探讨在 MCT 诱导的大鼠 PAH 中炎症过程的特征。
成年雄性 Sprague-Dawley 大鼠接受单次 MCT（50mg/kg，ip）注射，在 MCT 注射后 3、6、9、12、15、18、21、24、27 和 30 天测量 PAH 和炎症生物标志物的发生情况。
从 MCT 注射后的第 6 天开始，平均肺动脉压逐渐升高，第 30 天增加一倍，同时伴有右心室肥厚和肺动脉重塑，呈时间依赖性。在 MCT 治疗后的前 6 天，仅促炎细胞因子 TNF-α、IL-1β增加，定义为急性炎症期，之后，促炎因子 TNF-α、IL-1β、IL-6、IL-12 和抗炎因子 Arg1、IL-10、TGF-β增加，定义为慢性炎症期。肺和肺泡灌洗液中的 M1/M2 巨噬细胞比值在第 6 天和第 30 天升高，此外，第 6 天高于第 30 天，PI3K/Akt 信号通路随着 PAH 的进展而增加，与促炎蛋白相关，这在一定程度上也揭示了 MCT 诱导的 PAH 的炎症特征。
MCT 注射诱导的 PAH 呈进行性进展，伴有持续性炎症，MCT 治疗后 6 天内为急性炎症期，之后为慢性炎症期。
