Hydrogen sulfide improves endothelial dysfunction by inhibiting the vicious cycle of NLRP3 inflammasome and oxidative stress in spontaneously hypertensive rats
Hydrogen sulfide improves endothelial dysfunction by inhibiting the vicious cycle of NLRP3 inflammasome and oxidative stress in spontaneously hypertensive rats
复制标题
硫化氢通过抑制NLRP3炎症小体和氧化应激的恶性循环改善自发性高血压大鼠的内皮功能障碍
DOI：
10.1097/hjh.0000000000002101
复制
发表时间：
2019-08-01
影响因子：
4.9
通讯作者：
Wu, Yuming
中科院分区：
文献类型：
--
作者：
Li, Jiabao;Teng, Xu;Wu, Yuming
目的：探讨硫化氢（H2S）是否能通过抑制炎症小体和氧化应激改善高血压患者内皮功能障碍。方法：自发性高血压大鼠（SHR）和正常Wistar-Kyoto大鼠（WKY）每天腹腔注射100 mmol/l氢硫化钠（NaHS），持续16周。测定收缩压、血浆丙二醛（MDA）和白细胞介素1 β (IL-1 β)水平。采用肾血管功能测定内皮依赖性收缩（EDC）和内皮依赖性舒张（EDR）。western blot检测NOX1、p67 Phox、Nrf2、SOD1、CAT、NLRP3、caspase-1、IL-1 β蛋白水平。利用人脐静脉内皮细胞（HUVECs）证实H2S对血管紧张素II （Ang II）诱导的细胞损伤的保护作用。结果：外源性NaHS可显著降低收缩压，改善受损的EDC和EDR。H2S降低了SHR中NLRP3炎性体的激活和氧化应激。H2S的内皮保护和抗氧化作用被脂多糖（NLRP3炎性体的诱导剂）所破坏。在huvec中，H2S显著改善了Ang ii诱导的细胞损伤、NLRP3炎性体活性和活性氧的产生。敲除Nrf2后，H2S的保护作用被消除。结论：H2S可抑制高血压患者氧化应激与炎症的恶性循环，进而改善内皮功能，改善高血压。我们的结果有助于揭示H2S在调节内皮功能中的重要作用，这可能是治疗高血压的新工具。
Objective: To elucidate whether by inhibiting inflammasome and oxidative stress, hydrogen sulfide (H2S) can ameliorate endothelial dysfunction with hypertension.Methods: Spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) were injected with 100 mmol/l sodium hydrosulfide (NaHS) intraperitoneally daily for 16 weeks. SBP and plasma malondialdehyde (MDA) and interleukin 1 beta (IL-1 beta) levels were measured. Renal vascular function was used to determine endothelial-dependent contraction (EDC) and endothelial-dependent relaxation (EDR). Protein levels of NOX1, p67 Phox, Nrf2, SOD1, CAT, NLRP3, caspase-1 and IL-1 beta were detected by western blot analysis. Human umbilical vein endothelial cells (HUVECs) were used to confirm the protective role of H2S against angiotensin II (Ang II)-induced cell injury.Results: Exogenous NaHS administration significantly reduced SBP and ameliorated damaged EDC and EDR. H2S reduced the activation of NLRP3 inflammasome and oxidative stress in SHR. The endothelial protective and antioxidant effect of H2S was abolished by lipopolysaccharide, an inducer of NLRP3 inflammasome. In HUVECs, H2S significantly ameliorated Ang II-induced cellular impairment, NLRP3 inflammasome activity and reactive oxygen species generation. After knocking down Nrf2, the protective effect of H2S was abolished.Conclusion: H2S could inhibit the vicious cycle of oxidative stress and inflammation in hypertension, and then improve endothelial function and ameliorated hypertension. Our results help to reveal the crucial role of H2S in regulating endothelial function, which might be a new tool for treating hypertension.