School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang 11800, Malaysia.
Department of Physiology, University College Cork, T12 K8AF Cork, Ireland
Biomolecules. 2021 Oct 19;11(10):1549. doi: 10.3390/biom11101549.
Our main objective was to investigate the effect of chronic administration of hydrogen sulphide donor (sodium hydrosulphide) on the expression of intercellular adhesion molecule-1 (ICAM-1) and concentration of nuclear factor-kappa B (NF-kB) in a renal ischemia-reperfusion injury (IRI) model of WKY and L-nitro-arginine-methyl-ester (L-NAME)-induced hypertensive rats. Sodium hydrosulphide (NaHS) was administered intraperitoneally (i.p.) for 35 days while cystathionine gamma lyase (CSE) inhibitor dL-propargylglycine (PAG) was administered at a single dose of 50 mg/kg. Animals were anesthetised using sodium pentobarbitone (60 mg/kg) and then prepared to induce renal ischemia by clamping the left renal artery for 30 min followed by 3 h of reperfusion. Pre-treatment with NaHS improved the renal functional parameters in both WKY and L-NAME-induced hypertensive rats along with reduction of blood pressure in hypertensive groups. Oxidative stress markers like malondialdehyde (MDA), total superoxide dismutase (T-SOD) and glutathione (GSH) were also improved by NaHS treatment following renal IRI. Levels of ICAM-1 and NF-kB concentration were reduced by chronic treatment with NaHS and increased by PAG administration after renal IRI in plasma and kidney. Treatment with NaHS improved tubular morphology and glomerulus hypertrophy. Pre-treatment with NaHS reduced the degree of renal IRI by potentiating its antioxidant and anti-inflammatory mechanism, as evidenced by decreased NF-kB concentration and downregulation of ICAM-1 expression.
我们的主要目的是研究慢性给予硫化氢供体（硫氢化钠）对肾缺血再灌注损伤（IRI）模型中 WKY 和 L-硝基精氨酸甲酯（L-NAME）诱导的高血压大鼠细胞间黏附分子-1（ICAM-1）表达和核因子-κB（NF-κB）浓度的影响。硫氢化钠（NaHS）通过腹腔内（i.p.）给药 35 天，而半胱氨酸γ裂解酶（CSE）抑制剂 dL-炔丙基甘氨酸（PAG）则以 50mg/kg 的单剂量给药。用戊巴比妥钠（60mg/kg）麻醉动物，然后通过夹闭左肾动脉 30 分钟，再灌注 3 小时来诱导肾缺血。NaHS 预处理可改善 WKY 和 L-NAME 诱导的高血压大鼠的肾功能参数，并降低高血压组的血压。氧化应激标志物如丙二醛（MDA）、总超氧化物歧化酶（T-SOD）和谷胱甘肽（GSH）在肾 IRI 后也通过 NaHS 治疗得到改善。在血浆和肾脏中，NaHS 的慢性治疗降低了 ICAM-1 和 NF-κB 浓度的水平，而 PAG 给药后则增加了肾 IRI 后的水平。NaHS 治疗改善了肾小管形态和肾小球肥大。NaHS 的预处理通过增强其抗氧化和抗炎机制减轻了肾 IRI 的程度，这表现在 NF-κB 浓度的降低和 ICAM-1 表达的下调。
