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考虑红细胞理化性质的原发性和继发性高血压大鼠的高血压和 FAAH 抑制剂治疗的影响。

Effects of hypertension and FAAH inhibitor treatment of rats with primary and secondary hypertension considering the physicochemical properties of erythrocytes.

机构信息

Faculty of Chemistry, University in Białystok, Białystok, Poland.

Department of Experimental Physiology and Pathophysiology, Medical University of Białystok, Białystok, Poland.

出版信息

Toxicol Mech Methods. 2020 May;30(4):297-305. doi: 10.1080/15376516.2020.1727595. Epub 2020 Feb 20.

Abstract

Hypertension is one of the most common cardiovascular diseases in the world and is associated with oxidative stress. The aim of this study was to examine the effect of the chronic administration of the fatty-acid amide hydrolase inhibitor (URB597-[3-(3-carbamoylphenyl)phenyl]-cyclohexylcarbamate) to rats with primary (SHRs - spontaneously hypertensive rats) and secondary (DOCA-salt - 11-desoxycorticosterone acetate-salt-induced hypertension) hypertension on the composition and physicochemical properties of erythrocytes membrane. Because changes in membrane composition lead to modifications of electrical charge what may affect cell functions, the levels of following components were determined: four classes of membrane phospholipids (by HPLC - high-performance liquid chromatograph), sialic acid (by resorcinol method), lipid peroxidation product - malondialdehyde (by GCMS - gas chromatography-mass spectrometry). The reduced levels of phospholipids and sialic acid, as well as the increased levels of malonodialdehyde observed in the erythrocyte membrane of rats with primary and secondary hypertension led to a decrease in the negative electrical charge of the membrane. Long-term administration of URB597 to SHRs and DOCA-salt-treated rats partially prevented changes caused by hypertension. Using theoretical equations and the dependence of cell surface charge density as a function of pH, total surface concentrations of acid and base groups and their association constants have been determined. Considering the changes in physicochemical parameters of erythrocyte membranes, URB597 can be considered a potential protective factor for erythrocytes in situations of metabolic changes associated with oxidative stress.

摘要

高血压是世界上最常见的心血管疾病之一,与氧化应激有关。本研究旨在探讨慢性给予脂肪酸酰胺水解酶抑制剂(URB597-[3-(3-氨甲酰基苯基)苯基]-环己基氨基甲酸酯)对原发性(SHR-自发性高血压大鼠)和继发性(DOCA-盐-11-去氧皮质酮醋酸盐-盐诱导的高血压)高血压大鼠红细胞膜组成和理化性质的影响。由于膜组成的变化导致电荷发生变化,这可能会影响细胞功能,因此测定了以下成分的水平:四类膜磷脂(通过 HPLC-高效液相色谱法)、唾液酸(通过间苯二酚法)、脂质过氧化产物-丙二醛(通过 GCMS-气相色谱-质谱法)。原发性和继发性高血压大鼠红细胞膜中观察到磷脂和唾液酸水平降低,丙二醛水平升高,导致膜负电荷减少。URB597 长期给予 SHRs 和 DOCA-盐处理的大鼠可部分预防高血压引起的变化。使用理论方程和细胞表面电荷密度与 pH 的关系,可以确定酸和碱基团的总表面浓度及其缔合常数。考虑到红细胞膜理化参数的变化,URB597 可被认为是与氧化应激相关的代谢变化情况下红细胞的潜在保护因素。

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