Department of Physiology and Pharmacology, Afzalipour Medical Faculty, and Physiology Research Center, Kerman University of Medical Sciences , Kerman, Iran.
Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Science , Kerman, Iran.
Clin Exp Hypertens. 2021 Apr 3;43(3):270-280. doi: 10.1080/10641963.2020.1860080. Epub 2020 Dec 15.
: Pulmonary arterial hypertension (PAH) is a disastrous disease that current treatments cannot prevent its progression. The present study investigated the effects of perillyl alcohol (PA), a natural monoterpene, on the experimental PAH in male Wistar rats. : Rats divided into eight groups of control, Monocrotaline (MCT), MCT+vehicle, and MCT+PA with doses of 20, 30, 40, 50, and 60 mg/kg. PAH was induced by a single injection of monocrotaline (60 mg/kg) on day 0. The animals in the groups of MCT+vehicle and MCT+PA received the vehicle or PA from day 22 to 42 once a day. On day 43, under general anesthesia, right ventricular systolic pressure (RVSP), as an index of pulmonary artery systolic pressure, and the ratio of the right ventricle to the left ventricle plus septum weight, as the right ventricular hypertrophy index (RVHI), were measured. Also, some histological and biochemical indices were assessed in the lung tissue. : MCT significantly ( < .001) enhanced the RVSP and RVHI compared to the control group (89.4 ± 8.2 vs 23 ± 3.3 mmHg & 0.63 ± 0.08 vs 0.26 ± 0.04 respectively). It also increased oxidative stress and inflammatory cytokines and reduced Bax/Bcl2 ratio. Treatment with PA significantly recovered RVSP and hypertrophy index and suppressed vascular cell proliferation, oxidant production, and inflammatory processes. : PA exerted noticeable protective and curative effects against MCT-induced PAH and pulmonary vascular remodeling through inhibiting cellular proliferation, oxidative stress, and inflammation. Therefore, PA can be considered as a new therapeutic goal for the treatment of PAH.
: 肺动脉高压（PAH）是一种灾难性疾病，目前的治疗方法无法阻止其进展。本研究探讨了天然单萜化合物香叶醇（PA）对雄性 Wistar 大鼠实验性 PAH 的影响。 : 将大鼠分为对照组、野百合碱（MCT）组、MCT+载体组和 MCT+PA 组（剂量分别为 20、30、40、50 和 60 mg/kg）。第 0 天，通过单次注射野百合碱（60 mg/kg）诱导 PAH。MCT+载体组和 MCT+PA 组的动物从第 22 天到第 42 天每天接受一次载体或 PA 治疗。第 43 天，在全身麻醉下，测量右心室收缩压（RVSP）作为肺动脉收缩压的指标和右心室与左心室加室间隔重量的比值，作为右心室肥厚指数（RVHI）。此外，还评估了肺组织中的一些组织学和生化指标。 : MCT 显著（<0.001）增加了 RVSP 和 RVHI，与对照组相比（89.4±8.2 与 23±3.3mmHg 和 0.63±0.08 与 0.26±0.04 分别）。它还增加了氧化应激和炎性细胞因子，降低了 Bax/Bcl2 比值。PA 治疗显著恢复了 RVSP 和肥大指数，并抑制了血管细胞增殖、氧化产物和炎症过程。 : PA 通过抑制细胞增殖、氧化应激和炎症对 MCT 诱导的 PAH 和肺血管重构产生了显著的保护和治疗作用。因此，PA 可以被认为是治疗 PAH 的一种新的治疗目标。
