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. 2020 May;66(3):250-256.
doi: 10.18097/PBMC20206603250.

[Study of the influence of etoxidol on expression of follistatin-like protein-1 (FSTL-1) in myocardium after experimental infarction in rats]

[Article in Russian]
Affiliations

[Study of the influence of etoxidol on expression of follistatin-like protein-1 (FSTL-1) in myocardium after experimental infarction in rats]

[Article in Russian]
E V Parfenova et al. Biomed Khim. 2020 May.

Abstract

In heart attack, FSTL-1 is actively secreted by cardiomyocytes, accelerates growth of heart myofibrils and stimulates of vascular endothelial growth factor expression. The aim of this work was to investigate the effect of Etoxidol on synthesis of FSTL-1 in rats after myocardial infarction. The experiments were performed on Wistar rats weighing 250-350 g with simulated myocardial infarction or intact (group 5). Animals of control groups (groups 1, 2) were treated with saline for 7 and 14 days; Ethoxidol (24 mg/kg) was injected to animals of experimental groups (group 3, 4) (the daily dose was 6.36 mg/animal) for 6 or 14 days. The injection volume was 0.2 ml. At the beginning and at the end of the study plasma concentrations of FSTL-1 were determined by the ELISA method. Myocardial FSTL-1 gene expression was determined by real-time PCR. At the end of the experiments, the hearts were also used for histochemical analysis. To determine the size of the scar formed after the modeled heart attack, we used the classic Mallory staining method. The results show that the development of experimental acute myocardial infarction is accompanied by a significant increase in FSTL-1 expression in the heart, which was detected on the 7th day and stored increased by 14 days after a heart attack. After therapy with Ethoxidol, a tendency to a decrease in the expression of FSTL-1 by the 14th day was observed; it coincided with the dynamics of the plasma protein FSTL-1 level. It can be assumed that the downregulation trend in the FSTL-1 expression is associated with a more effective repair process after a heart attack, since FSTL-1 increases precisely in response to myocardial damage and decreases when the incentives for its expression from damaged heart tissue are reduced. Indirectly, this assumption is confirmed by the detected tendency to reduce the size of post-infarction fibrosis in the treatment with Ethoxidol. The results indicate the ability of Ethoxidol to influence FSTL-1 synthesis of in rats after myocardial infarction.

Pri infarkte FSTL-1 aktivno sekretiruetsia kardiomitsitami, uskoriaet rost miofibrill serdtsa i stimuliruet ékspressiiu faktora rosta éndoteliia sosudov. Tsel' raboty zakliuchalas' v poiske lekarstvennogo sredstva, sposobnogo vliiat' na sintez FSTL-1 u krys posle infarkta miokarda. Opyty provedeny na krysakh linii Wistar massoĭ 250-350 g s modelirovannym infarktom miokarda i bez infarkta (gruppa 5). V techenie 7 i 14 dneĭ zhivotnym kontrol'nykh grupp (gruppy 1, 2) podkozhno vvodili fiziologicheskiĭ rastvor, a zhivotnym éksperimental'nykh grupp (gruppy 3, 4) vvodili étoksidol 1 raz v sutki v doze 24 mg/kg (sutochnaia doza sostavliala 6,36 mg/na zhivotnoe; sredniaia massa zhivotnogo — 265 g). Vvodimyĭ ob"em sostavlial 200 mkl, kontsentratsiia rastvora — 31,8 mg/ml. V den' operatsii preparat vvodili vnutrivenno, posleduiushchie 7 i 14 dneĭ — podkozhno. V nachale i v kontse issledovaniia kontsentratsiiu FSTL-1 v plazme krovi opredeliali metodom IFA. Ékspressiiu gena FSTL-1 opredeliali metodom PTsR. Po okonchanii opytov serdtsa ispol'zovali dlia gistokhimicheskogo analiza. Dlia opredeleniia razmerov sformirovavshegosia posle infarkta rubtsa ispol'zovali klassicheskiĭ metod okrashivaniia po Mallori. Poluchennye rezul'taty pokazyvaiut, chto razvitie ostrogo éksperimental'nogo infarkta miokarda soprovozhdaetsia znachitel'nym uvelicheniem ékspressii FSTL-1 v serdtse, kotoroe registriruetsia na 7 den' i sokhraniaetsia povyshennym na 14 den' posle infarkta. Posle terapii étoksidolom k 14 dniu otmechaetsia tendentsiia k snizheniiu ékspressii FSTL-1, chto sovpadaet s dinamikoĭ urovnia belka FSTL-1 v plazme krovi. Mozhno predpolozhit', chto tendentsiia k snizheniiu ékspressii FSTL-1 sviazana s bolee uspeshnym protsessom reparatsii posle infarkta, tak kak FSTL-1 povyshaetsia imenno v otvet na povrezhdenie miokarda i snizhaetsia, kogda stimuly k ego ékspressii iz povrezhdennoĭ tkani serdtsa umen'shaiutsia. Kosvenno éto predpolozhenie podtverzhdaetsia obnaruzhennoĭ tendentsieĭ k umen'sheniiu razmera postinfarktnogo fibroza pri lechenii étoksidolom. Poluchennye rezul'taty svidetel'stvuiut o sposobnosti étoksidola vliiat' na sintez FSTL-1 u krys posle infarkta miokarda.

Keywords: ethoxidol; follistatin-like protein 1; myocardial infarction.

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