Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China.
Department of Pathophysiology, Harbin Medical University, Harbin, 150080, China.
Biochem Biophys Res Commun. 2021 Jan 22;537:7-14. doi: 10.1016/j.bbrc.2020.12.059. Epub 2020 Dec 28.
Hydrogen sulfide (HS) prevents platelet activation and neutrophils extracellular traps (NETs) formation. However, the mechanism of sodium hydrosulfide (NaHS, a donor that produces HS) inhibits the formation of NETs in hyperhomocysteinemia (HHcy) rats has not been previously investigated. In the experiment, the expressions of HMGB1 of platelets, the expressions of TLR4, PAD4 and the phosphor-p38 of neutrophils were measured. The NETs formations, the concentration of DNA in the serum and the culture solution of cultured neutrophils which was stimulated by platelet-rich plasma (PRP) were tested. Additionally, the cellular ROS level and SOD activity were detected. The platelets were activated and the expression of HMGB1 of platelets and NETs formation, the concentration of DNA, and the expressions of TLR4, phosphor-p38 and PAD4, the ROS level were all increased while the activity of SOD decreased in the HHcy group compared to the control group. NaHS significantly inhibited the activation of platelets, the production of ROS and the formation of NETs in neutrophils, reversed the expressions of HMGB1, TLR4, phosphor-p38, PAD4 and decreased concentration of DNA which was caused by high homocysteine. Our results demonstrate that the donor of HS inhibits NETs formation of neutrophils via the HMGB1/TLR4/p38 MAPK/ROS pathway in hyperhomocysteinemia.
硫化氢 (HS) 可防止血小板活化和中性粒细胞细胞外陷阱 (NETs) 的形成。然而，先前并未研究过硫氢化钠 (NaHS，一种产生 HS 的供体) 抑制高同型半胱氨酸血症 (HHcy) 大鼠中 NETs 形成的机制。在实验中，测量了血小板中 HMGB1 的表达、中性粒细胞中 TLR4、PAD4 和 p38 磷酸化的表达。测试了富血小板血浆 (PRP) 刺激培养的中性粒细胞形成的 NETs、血清和培养溶液中 DNA 的浓度。此外，还检测了细胞内 ROS 水平和 SOD 活性。与对照组相比，HHcy 组血小板被激活，血小板中 HMGB1 的表达和 NETs 的形成、DNA 的浓度以及 TLR4、p38 磷酸化和 PAD4 的表达增加，而 SOD 的活性降低。NaHS 显著抑制血小板的活化、ROS 的产生和中性粒细胞中 NETs 的形成，逆转了高同型半胱氨酸引起的 HMGB1、TLR4、p38 MAPK/ROS 通路相关的 TLR4、p38 磷酸化和 PAD4 的表达和 DNA 浓度的增加。我们的结果表明，HS 的供体通过 HMGB1/TLR4/p38 MAPK/ROS 通路抑制高同型半胱氨酸血症中的中性粒细胞 NETs 的形成。
