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影响大鼠宫内缺氧后出生后早期一氧化氮生成及生物利用度的药物的心脏保护活性

Cardioprotective Activity of Pharmacological Agents Affecting NO Production and Bioavailability in the Early Postnatal Period after Intrauterine Hypoxia in Rats.

作者信息

Popazova Olena, Belenichev Igor, Bukhtiyarova Nina, Ryzhenko Victor, Oksenych Valentyn, Kamyshnyi Aleksandr

机构信息

Department of Histology, Cytology and Embryology, Zaporizhzhia State Medical and Pharmaceutical University, 69000 Zaporizhzhia, Ukraine.

Department of Pharmacology and Medical Formulation with Course of Normal Physiology, Zaporizhzhia State Medical and Pharmaceutical University, 69000 Zaporizhzhia, Ukraine.

出版信息

Biomedicines. 2023 Oct 21;11(10):2854. doi: 10.3390/biomedicines11102854.

Abstract

Intrauterine hypoxia in newborns leads to a multifaceted array of alterations that exert a detrimental impact on the cardiovascular system. The aim of this research was to assess the cardioprotective effects of modulators of the nitric oxide (NO) system, including L-arginine, Thiotriazoline, Angiolin, and Mildronate, during the early postnatal period following intrauterine hypoxia. Methods: The study involved 50 female white rats. Pregnant female rats were given a daily intraperitoneal dose of 50 mg/kg of sodium nitrite starting on the 16th day of pregnancy. A control group of pregnant rats received saline instead. The resulting offspring were divided into the following groups: Group 1-intact rats; Group 2-rat pups subjected to prenatal hypoxia (PH) and daily treated with physiological saline; and Groups 3 to 6-rat pups exposed to prenatal hypoxia and treated daily from the 1st to the 30th day after birth. Nitrotyrosine levels, eNOS, iNOS, and NO metabolites were evaluated using ELISA; to measure the expression levels of iNOS mRNA and eNOS mRNA, a PCR test was utilized. Results: Angiolin enhances the expression of eNOS mRNA and boosts eNOS activity in the myocardium of rats with ischemic conditions. Arginine and particularly Thiotriazoline exhibited a consistent impact in restoring normal parameters of the cardiac nitroxidergic system following PH. Mildronate notably raised iNOS mRNA levels and notably reduced nitrotyrosine levels, providing further support for its antioxidative characteristics.

摘要

新生儿宫内缺氧会导致一系列多方面的改变,对心血管系统产生有害影响。本研究的目的是评估一氧化氮(NO)系统调节剂,包括L-精氨酸、硫代三唑啉、血管生成素和米多君,在宫内缺氧后出生后早期的心脏保护作用。方法:该研究涉及50只雌性白色大鼠。从妊娠第16天开始,给怀孕的雌性大鼠每日腹腔注射50mg/kg亚硝酸钠。一组怀孕大鼠对照组接受生理盐水代替。将产生的后代分为以下几组:第1组为未处理的大鼠;第2组为产前缺氧(PH)的幼鼠,每天用生理盐水处理;第3至6组为暴露于产前缺氧且从出生后第1天至第30天每天接受处理的幼鼠。使用酶联免疫吸附测定法(ELISA)评估硝基酪氨酸水平、内皮型一氧化氮合酶(eNOS)、诱导型一氧化氮合酶(iNOS)和NO代谢产物;为了测量iNOS mRNA和eNOS mRNA的表达水平,采用了聚合酶链反应(PCR)检测。结果:血管生成素增强了缺血状态下大鼠心肌中eNOS mRNA的表达并提高了eNOS活性。精氨酸,特别是硫代三唑啉,在恢复PH后心脏硝氧化系统的正常参数方面表现出一致的作用。米多君显著提高了iNOS mRNA水平并显著降低了硝基酪氨酸水平,进一步支持了其抗氧化特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/563a/10604160/6bd4c4d5f4ad/biomedicines-11-02854-g001.jpg

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