在初步刺激肝脏酶系统的条件下,药物单克隆钠诱导大鼠肺动脉高压模型时靶器官的形态变化特征

A. V. Zagrebelnaya, O. V. Shcheblykina, A. A. Bolgov
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The purpose of this work was to determine differences in morphological changes in the myocardium and pulmonary vessels of rats in which pulmonary hypertension was modeled using monocrotaline with and without additional stimulation of liver enzymes. Material and methods. The study was conducted on 24 mature male Wistar rats. The animals were divided into 4 groups of 6 rats. Group 1 was represented by intact animals. In groups 2, 3 and 4, modeling of pulmonary hypertension in rats was carried out with a single subcutaneous injection of an aqueous-alcohol solution of monocrotaline at a dose of 60 mg/kg. In order to induce cytochrome P450 in groups 3 and 4, animals were intragastrically administered phenobarbital for one and three days, respectively. Results and discussion. 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引用次数: 0

摘要

肺动脉高压是一种以肺循环压力逐渐升高为特征的疾病。肺动脉高压最简单、最常见的实验模型是单克洛林模型。它是基于细胞色素 P450 将肝脏中的单克巴林转化为内皮毒性单克巴林吡咯的过程,而单克巴林吡咯又会损害肺血管内皮,导致肺循环循环障碍,形成肺动脉高压。因此,对细胞色素 P450 进行额外的预刺激可能会增加单克洛汀模型的稳定性和代表性。本研究的目的是确定使用单克洛塔林建立肺动脉高压模型的大鼠心肌和肺血管形态学变化的差异,以及是否对肝酶进行额外刺激。材料和方法研究对象为 24 只成熟雄性 Wistar 大鼠。这些动物被分为 4 组,每组 6 只。第 1 组为完好无损的动物。在第 2、第 3 和第 4 组中,以 60 毫克/千克的剂量向大鼠皮下注射一缩胺水乙醇溶液,对大鼠进行肺动脉高压模型试验。为了诱导第 3 组和第 4 组大鼠体内的细胞色素 P450,分别给它们灌胃苯巴比妥 1 天和 3 天。结果与讨论肝酶初步刺激 1 天组和 3 天组的心肌细胞核面积分别为 22.78 ± 3.4 µm2 和 23.63 ± 3.72 µm2,与对照组和第 2 组的相应值有显著差异。 在测定小口径肺动脉内膜厚度指数时也发现了类似的结果--初步刺激 1 天组和 3 天组分别为 58.32 ± 10.02 % 和 76.44 ± 18.55 %。除量变外,还发现了质变:随着细胞色素 P450 的进一步激活,心肌间质纤维化和心肌炎更加严重,肺部的 "单克隆综合征 "症状更快出现和发展。结论根据所获得的数据,可以推测细胞色素 P450 的初步作用会增加单克隆肾上腺素肺动脉高压模型形态变化的稳定性、可重复性和严重性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Morphological features of changes in target organs during pharmacological monocrotaline-induced modeling of pulmonary hypertension in rats under conditions of preliminary stimulation of liver enzymatic systems
Pulmonary hypertension is a condition characterized by a progressive increase in pressure in the pulmonary circulation. The simplest and most common experimental model of pulmonary hypertension is the monocrotaline model. It is based on the process of transformation of monocrotaline in the liver by cytochrome P450 into endothelial toxic monocrotaline pyrrole, which in turn, damaging the endothelium of the pulmonary vessels, leads to circulatory disorders in the pulmonary circulation and the formation of pulmonary hypertension. Thus, additional prestimulation of cytochrome P450 may increase the stability and representativeness of the monocrotaline model. The purpose of this work was to determine differences in morphological changes in the myocardium and pulmonary vessels of rats in which pulmonary hypertension was modeled using monocrotaline with and without additional stimulation of liver enzymes. Material and methods. The study was conducted on 24 mature male Wistar rats. The animals were divided into 4 groups of 6 rats. Group 1 was represented by intact animals. In groups 2, 3 and 4, modeling of pulmonary hypertension in rats was carried out with a single subcutaneous injection of an aqueous-alcohol solution of monocrotaline at a dose of 60 mg/kg. In order to induce cytochrome P450 in groups 3 and 4, animals were intragastrically administered phenobarbital for one and three days, respectively. Results and discussion. The area of cardiomyocyte nuclei in the groups with one- and three-day preliminary stimulation of liver enzymes was 22.78 ± 3.4 and 23.63 ± 3.72 µm2 , respectively, significantly different from the corresponding values of the control group and group 2. Similar results were revealed when determining the index of the thickness of the medial membrane of small-caliber pulmonary arteries – 58.32 ± 10.02 and 76.44 ± 18.55 % in the groups with one- and three-day preliminary stimulation, respectively. In addition to quantitative changes, qualitative changes were also noted: with additional activation of cytochrome P450, interstitial fibrosis and myocarditis more intensively formed in the myocardium, and signs of “monocrotaline syndrome” more rapidly arose and progressed in the lungs. Conclusions. Based on the data obtained, it can be assumed that preliminary cytochrome P450 causes an increase in the stability, reproducibility and severity of morphological changes in the monocrotaline model of pulmonary hypertension.
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