丙戊酸钠通过调节缺氧诱导因子-1α的表达抑制致死性烫伤大鼠心肌细胞的凋亡

IF 0.7 4区 医学 Q4 PHARMACOLOGY & PHARMACY
Xiangxi Meng, Hailing Wen, Sen Hu, Jinguang Zheng
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引用次数: 0

摘要

本研究评估了丙戊酸钠(VPA)对致死性烫伤大鼠心肌细胞凋亡的抑制作用。制作体表总面积为 50%的三度全厚烫伤模型,将 48 只雄性 SD 大鼠随机分为三组(n = 16),假组和烫伤组腹腔注射 0.25ml生理盐水,烫伤+VPA组在烫伤后腹腔注射VPA(300 mg/kg),每组按烫伤后3h和6h两个观察时间点分为两个亚组(n=8)。观察心肌细胞凋亡情况,并测定心肌组织中一氧化氮(NO)、半胱氨酸蛋白酶-3(caspase-3)活性、缺氧诱导因子-1α(HIF-1α)、诱导型一氧化氮合酶(iNOS)、BCL2/腺病毒E1B互作蛋白3(BNIP3)和caspase-3蛋白水平。与假烫组相比,重度烫伤组CK-MB、心肌细胞凋亡率、caspase-3活性和蛋白水平、NO含量和HIF-1α信号通路蛋白均升高;而VPA可降低CK-MB、心肌细胞凋亡率并抑制HIF-1α信号通路蛋白的表达。总之,这些结果表明,VPA 可抑制致死性烫伤大鼠早期心肌细胞凋亡,减轻心肌损伤,这可能与 HIF-1α 信号通路的调节有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Sodium valproate inhibited apoptosis in lethally scalded rat cardiomyocytes by regulating hypoxia-inducible factor-1α expression.

This study assessed the inhibitory effect of sodium valproate (VPA) on apoptosis of cardiomyocytes in lethally scalded rats. The model of a 50% total body surface area (TBSA) third-degree full-thickness scald was produced, 48 male SD rats were randomly divided into three groups (n = 16), the sham group and the scald group were given an intraperitoneal injection of 0.25ml of saline, the scald +VPA group was given an intraperitoneal injection of VPA (300 mg/kg) after scalded, Each group was subdivided into two subgroups (n=8) according to the two observation time points of 3h and 6h after scald. Apoptotic cardiomyocytes were observed, and myocardial tissue levels of nitric oxide (NO), cysteine protease-3 (caspase-3) activity, hypoxia-inducible factor-1α (HIF-1α), inducible nitric oxide synthase (iNOS), BCL2/adenovirus E1B interacting protein 3 (BNIP3) and caspase-3 protein were measured. Compared with sham scald group, severe scald elevated CK-MB, cardiomyocyte apoptosis rate, caspase-3 activity and protein levels, NO content, and HIF-1α signalling pathway proteins; whereas VPA decreased CK-MB, cardiomyocyte apoptosis rate and inhibited HIF-1α signalling pathway protein expression. In conclusion, these results suggested that VPA inhibited early cardiomyocyte apoptosis and attenuated myocardial injury in lethally scalded rats, which may be related to the regulation of the HIF-1α signalling pathway.

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来源期刊
CiteScore
1.40
自引率
12.50%
发文量
211
审稿时长
4.5 months
期刊介绍: Pakistan Journal of Pharmaceutical Sciences (PJPS) is a peer reviewed multi-disciplinary pharmaceutical sciences journal. The PJPS had its origin in 1988 from the Faculty of Pharmacy, University of Karachi as a biannual journal, frequency converted as quarterly in 2005, and now PJPS is being published as bi-monthly from January 2013. PJPS covers Biological, Pharmaceutical and Medicinal Research (Drug Delivery, Pharmacy Management, Molecular Biology, Biochemical, Pharmacology, Pharmacokinetics, Phytochemical, Bio-analytical, Therapeutics, Biotechnology and research on nano particles.
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