Suppression of Aseptic Inflammation Reduces the Severity of Pulmonary Artery Remodeling and Improves the Clinical Course of Experimental Chronic Thromboembolic Pulmonary Hypertension

IF 0.6 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Evolutionary Biochemistry and Physiology Pub Date : 2024-06-26 DOI:10.1134/s002209302403030x

A. A. Karpov, A. A. Krylov, L. A. Shilenko, A. M. Mihailova, D. D. Vaulina, D. Yu. Ivkin, N. P. Isakova, A. V. Vorotilov, N. Yu. Semenova, V. A. Zinserling, M. M. Galagudza

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Abstract

Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of pulmonary embolism, characterized by high blood pressure in the pulmonary artery combined with impaired lysis of fibrin clots. Previously, the presence of aseptic inflammation in CTEPH was found in the wall of the pulmonary artery branches, as well as perivascularly. However, the role of this inflammation in shaping CTEPH is unknown. The aim of the work was to study the effect of aseptic inflammation on CTEPH formation and progression. The experiments were carried out on male Wistar rats (n = 54). The CTEPH model was reproduced by repeated intravenous administration of partially biodegradable microspheres (MS). Immediately after the last MS administration, all animals were randomly allocated into four groups: (1) control (c.CTEPH) group—physiological saline was administered intramuscularly (i.m.) for 6 weeks; (2) low-dose prednisolone (LDP) group—prednisolone was administered i.m. at a dose of 1.5 mg/kg; (3) high-dose prednisolone (HDP) group—prednisolone was administered i.m. at a dose of 6 mg/kg; (4) healthy or intact (INT) group. After 6 weeks, there were performed the treadmill test, transthoracic echocardiography, cardiac catheterization with blood pressure manometry, and lung tissue histological examination. In a separate series of experiments, the degree of vascular wall and perivascular space inflammatory infiltration was assessed immunohistochemically. In LDP group, the vascular wall hypertrophy index (HI) and the percentage of collagen fibers in the vascular wall were reduced compared to the control group, with the HI being reduced significantly greater than in HDP group. In the latter, there was revealed a positive effect of high-dose prednisolone on the percentage of collagen fibers in the vascular wall, with this parameter being non-significantly different from that in intact animals. By immunohistochemical data, low-dose prednisolone effectively suppressed inflammatory infiltration of the vascular wall and perivascular space. Thus, we revealed the ability of low-dose prednisolone to reduce the degree of remodeling of the pulmonary artery branches by suppressing aseptic inflammation.

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抑制无菌性炎症可降低肺动脉重塑的严重程度并改善实验性慢性血栓栓塞性肺动脉高压症的临床病程

摘要慢性血栓栓塞性肺动脉高压（CTEPH）是肺栓塞的一种并发症，其特点是肺动脉血压高，纤维蛋白凝块的溶解功能受损。以前，在 CTEPH 中发现肺动脉分支壁和血管周围存在无菌性炎症。然而，这种炎症在形成 CTEPH 中的作用尚不清楚。这项工作的目的是研究无菌性炎症对 CTEPH 形成和发展的影响。实验在雄性 Wistar 大鼠（n = 54）身上进行。通过反复静脉注射部分可生物降解的微球（MS）再现了 CTEPH 模型。最后一次给药后，立即将所有动物随机分为四组：（1）对照（c.CTEPH）组-生理盐水肌肉注射（i.m.(2) 低剂量泼尼松龙组（LDP）--泼尼松龙剂量为 1.5 毫克/千克，肌肉注射；(3) 高剂量泼尼松龙组（HDP）--泼尼松龙剂量为 6 毫克/千克，肌肉注射；(4) 健康或完好组（INT）。6 周后，进行跑步机试验、经胸心动图检查、心导管检查和血压测量，以及肺组织学检查。在另一系列实验中，对血管壁和血管周围间隙的炎症浸润程度进行了免疫组化评估。与对照组相比，LDP 组血管壁肥厚指数（HI）和血管壁胶原纤维百分比均有所降低，其中 HI 的降低幅度明显高于 HDP 组。在后者中，大剂量泼尼松龙对血管壁胶原纤维百分比有积极影响，该参数与完整动物无显著差异。免疫组化数据显示，小剂量泼尼松龙能有效抑制血管壁和血管周围间隙的炎症浸润。因此，我们发现小剂量泼尼松龙可以通过抑制无菌性炎症来减轻肺动脉分支的重塑程度。

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来源期刊

Journal of Evolutionary Biochemistry and Physiology 生物-进化生物学

自引率

33.30%

发文量

110

审稿时长

6-12 weeks

期刊介绍： Journal of Evolutionary Biochemistry and Physiology publishes original experimental and theoretical and review articles related to evolution of the main forms of metabolism in connection with life origin; comparative and ontogenetic physiology and biochemistry, biochemical evolution of animal world; as well as evolution of functions; morphology, pharmacology, pathophysiology and ecological physiology. The journal welcomes manuscripts from all countries in the English or Russian language.