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硫化氢通过减少雄性大鼠氧化应激保护海马 CA1 神经元免受铅介导的神经元损伤。

Hydrogen sulfide protects hippocampal CA1 neurons against lead mediated neuronal damage via reduction oxidative stress in male rats.

机构信息

Psychiatry and Behavioral Sciences, Addiction Research Institute, Mazandaran University of Medical Sciences, Iran.

Sexual Health and Fertility Research Center, Shahroud University of Medical Sciences, Shahroud, Iran.

出版信息

J Chem Neuroanat. 2021 Mar;112:101917. doi: 10.1016/j.jchemneu.2020.101917. Epub 2021 Jan 12.

Abstract

H2S plays vital roles in modulation brain function. It is associated with antioxidant and anti-inflammatory properties. We assessed the H2S impact on spatial learning and memory deficit and cell death due to lead exposure, and probable mechanisms of action. The 36 male Wistar rats that (200-220 g), were in random assigned to 3 groups, control group (12 rats), lead acetate group (12 rats), and lead acetate +H2S groups (NaHS as a H2S donor; 5/6 mg/kg; 12 rats). Administration of lead to rats was performed through acute lead poisoning (25 mg/kg of lead acetate, IP through 3 days). Using male Morris water maze, their spatial learning and memory function were measured. We carried out ELISA method to calculate TNF-α and antioxidant enzymes level. Immunohistochemical staining was applied for evaluating the caspase-3 expression levels. Treatment with H2S improved learning and memory impairment in Pb-exposed rats (P<0.05). H2S treatment suppressed Pb-related apoptosis in the hippocampal CA1 subfield (P<0.01). Also, the TNF-α over-expression in the CA1 region of hippocampus due to lead exposure showed a significant reduction (P<0.05) after administrating H2S. Simultaneously, H2S treatment reduced the MDA levels, enhanced SOD, GSH level than the Pb-exposed group in hippocampus (P<0.05). H2S was able to significantly improve Pb-related spatial learning and memory deficit, and neuronal cell death in the CA1 region of hippocampus in the male rats at least partly by reducing oxidative stress and TNF.

摘要

H2S 在调节大脑功能方面发挥着重要作用。它与抗氧化和抗炎特性有关。我们评估了 H2S 对铅暴露引起的空间学习和记忆缺陷和细胞死亡的影响,以及可能的作用机制。36 只雄性 Wistar 大鼠(体重 200-220g)被随机分为 3 组:对照组(12 只大鼠)、醋酸铅组(12 只大鼠)和醋酸铅+H2S 组(NaHS 作为 H2S 供体;5/6mg/kg;12 只大鼠)。通过急性铅中毒(腹腔注射 25mg/kg 的醋酸铅,连续 3 天)向大鼠给予铅。使用雄性 Morris 水迷宫,测量它们的空间学习和记忆功能。我们采用 ELISA 法计算 TNF-α 和抗氧化酶水平。应用免疫组织化学染色评估 caspase-3 表达水平。H2S 治疗改善了 Pb 暴露大鼠的学习和记忆障碍(P<0.05)。H2S 治疗抑制了 Pb 相关的海马 CA1 区细胞凋亡(P<0.01)。此外,Pb 暴露导致海马 CA1 区 TNF-α 的过度表达在给予 H2S 后显著降低(P<0.05)。同时,H2S 处理降低了海马 MDA 水平,增强了 SOD、GSH 水平,优于 Pb 暴露组(P<0.05)。H2S 能够显著改善雄性大鼠 Pb 相关的空间学习和记忆缺陷,以及海马 CA1 区的神经元细胞死亡,至少部分是通过降低氧化应激和 TNF 实现的。

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