七氟醚可预防大鼠肺动脉高压中的肺血管重塑和右心室功能障碍。
Sevoflurane prevents pulmonary vascular remodeling and right ventricular dysfunction in pulmonary arterial hypertension in rats.
作者信息
Zhai Wenqian, Li Yunfei, Luo Yongjuan, Gao Weidong, Liu Shan, Han Jiange, Geng Jie
机构信息
Department of Anesthesiology, Tianjin Chest Hospital Tianjin 300222, China.
Department of Ultrasonics, Tianjin Chest Hospital Tianjin 300222, China.
出版信息
Am J Transl Res. 2021 Oct 15;13(10):11302-11315. eCollection 2021.
BACKGROUND
The cardioprotective properties of sevoflurane have been reported in studies of the left ventricle. However, whether this volatile anesthetic would also be beneficial for pulmonary vascular remodeling and associated right ventricular hypertrophy (RVH) remained to be explored. Here, we investigated the potential benefit of sevoflurane to right heart function in experimental pulmonary arterial hypertension (PAH).
METHODS
Adult Wistar rats received one dose peritoneal injection of monocrotaline (MCT, 60 mg/kg) or the equal volume of normal saline. Two weeks later, rats were treated with sevoflurane or sham exposure. PAH status and cardiac function were assessed by echocardiography weekly, and the body weight (BW) was monitored every week. After 6 weeks of exercise, Fulton's index calculation, histological observation, IL-6 and TNF-α immunohistochemical analyses, evaluation of MDA, SOD and GSH-Px levels and NF-κB and MAPK active determination were performed in lung and RV tissue samples.
RESULTS
MCT induced pulmonary vascular remodeling, RVH, increased Fulton's index (<0.01), and right ventricular failure (RVF) in rats. Animals inhaled sevoflurane had an increased cardiac output (<0.05) and lower incidence of RVF (<0.05). Also, these animals had a reduced RVEDD, RVWTd and PAID (<0.05), increased PV (<0.05), reduced wall thickness and vascular wall area of pulmonary small vascular (vascular external diameter 50-150 um) (<0.01), reduced RV fibrosis, and increased RV cardiomyocyte area (<0.01). Furthermore, sevoflurane reduced IL-6 and TNF-α expression in lungs and heart (<0.01), decreased level of MDA (<0.01) and increased activity of SOD and GSH-Px (<0.01). In addition, it decreased the activities of NF-κB and MAPK pathways (<0.01).
CONCLUSION
Sevoflurane reduces pulmonary vascular remodeling and RVH in PAH induced by MCT in rats. This effect is likely due to down-regulation of inflammatory factors IL-6 and TNF-α, reduced level of oxidative stress and the inhibition of NF-κB and MAPK pathways.
背景
七氟醚的心脏保护特性已在左心室研究中得到报道。然而，这种挥发性麻醉剂对肺血管重塑及相关右心室肥厚（RVH）是否也有益仍有待探索。在此，我们研究了七氟醚对实验性肺动脉高压（PAH）中右心功能的潜在益处。
方法
成年Wistar大鼠腹腔注射一剂野百合碱（MCT，60mg/kg）或等体积的生理盐水。两周后，大鼠接受七氟醚处理或假暴露。每周通过超声心动图评估PAH状态和心脏功能，每周监测体重（BW）。运动6周后，对肺和右心室组织样本进行Fulton指数计算、组织学观察、IL-6和TNF-α免疫组化分析、MDA、SOD和GSH-Px水平评估以及NF-κB和MAPK活性测定。
结果
MCT诱导大鼠肺血管重塑、RVH、Fulton指数升高（<0.01）以及右心室衰竭（RVF）。吸入七氟醚的动物心输出量增加（<0.05），RVF发生率降低（<0.05）。此外，这些动物的右心室舒张末期内径、右心室壁厚度和肺动脉内径减小（<0.05），肺血管阻力增加（<0.05），肺小血管（血管外径50 - 150μm）的壁厚和血管壁面积减小（<0.01），右心室纤维化减轻，右心室心肌细胞面积增加（<0.01）。此外，七氟醚降低了肺和心脏中IL-6和TNF-α的表达（<0.01），降低了MDA水平（<0.01），增加了SOD和GSH-Px的活性（<0.01）。此外，它降低了NF-κB和MAPK途径的活性（<0.01）。
结论
七氟醚可减轻MCT诱导的大鼠PAH中的肺血管重塑和RVH。这种作用可能是由于炎症因子IL-6和TNF-α的下调、氧化应激水平的降低以及NF-κB和MAPK途径的抑制。
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