Borodzicz-Jażdżyk Sonia, Kołodzińska Agnieszka, Czarzasta Katarzyna, Wojciechowska Małgorzata, Główczyńska Renata, Szczepankiewicz Benedykt, Puchalska Liana, Opolski Grzegorz, Cudnoch-Jędrzejewska Agnieszka
Chair and Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, 1b Banacha Street, 02-097 Warsaw, Poland.
1st Chair and Department of Cardiology, Medical University of Warsaw, 1a Banacha Street, 02-097 Warsaw, Poland.
Biomedicines. 2023 Jul 21;11(7):2060. doi: 10.3390/biomedicines11072060.
Takotsubo syndrome (TTS) is associated with inflammatory response, therefore the aim of the study was to evaluate the presence and dynamics of inflammatory-associated forms of cell death, necroptosis, and pyroptosis in the female rat model of isoprenaline (ISO)-induced TTS. TTS was induced in female Sprague Dawley rats (n = 36) by ISO 150 mg/kg intraperitoneally. Animals were divided into four groups: TTSO (TTS+ovariectomy; n = 10), TTSP (TTS+sham operation; n = 10), CO (0.9% NaCl+ovariectomy; n = 8), CP (0.9% NaCl+sham operation; n = 8). Histopathological analysis, evaluation of plasma concentration, and myocardial expression of pyroptosis- and necroptosis-associated proteins were performed. TTSO and TTSP groups had higher plasma concentrations of interleukin-1β in comparison with the controls. Low myocardial protein expression of mixed lineage kinase domain-like pseudokinase (MLKL), caspase-1 (Casp-1), and calcium/calmodulin-dependent kinase type II isoform delta (CAMKIIδ) was visible 6 and/or 12 h post-ISO. Twenty-four hours post-ISO, high myocardial and vascular protein expression of CAMKIIδ was visible in TTSO but not TTSP rats, while high myocardial expression of MLKL and Casp-1 was visible both in TTSO and TTSP rats. The course of TTS is associated with activation of inflammatory-associated programmed cell death, necroptosis, and pyroptosis, therefore inflammation may be a primary response occurring simultaneously with cardiomyocyte death in TTS.
应激性心肌病（TTS）与炎症反应相关，因此本研究的目的是评估在异丙肾上腺素（ISO）诱导的TTS雌性大鼠模型中，炎症相关的细胞死亡形式、坏死性凋亡和焦亡的存在及动态变化。通过腹腔注射150 mg/kg ISO诱导雌性Sprague Dawley大鼠（n = 36）发生TTS。动物被分为四组：TTSO（TTS+卵巢切除术；n = 10），TTSP（TTS+假手术；n = 10），CO（0.9%氯化钠+卵巢切除术；n = 8），CP（0.9%氯化钠+假手术；n = 8）。进行了组织病理学分析、血浆浓度评估以及焦亡和坏死性凋亡相关蛋白的心肌表达评估。与对照组相比，TTSO和TTSP组的血浆白细胞介素-1β浓度更高。在ISO注射后6小时和/或12小时，可见混合谱系激酶结构域样假激酶（MLKL）、半胱天冬酶-1（Casp-1）和钙/钙调蛋白依赖性蛋白激酶IIδ型（CAMKIIδ）的心肌蛋白表达较低。在ISO注射后24小时，在TTSO大鼠中可见CAMKIIδ的心肌和血管蛋白高表达，而在TTSP大鼠中未见，而在TTSO和TTSP大鼠中均可见MLKL和Casp-1的心肌高表达。TTS的病程与炎症相关的程序性细胞死亡、坏死性凋亡和焦亡的激活有关，因此炎症可能是TTS中心肌细胞死亡同时发生的主要反应。
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