Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Crit Care Med. 2010 Feb;38(2):619-28. doi: 10.1097/CCM.0b013e3181c0df00.
To investigate the interaction and involvement of hydrogen sulfide and transient receptor potential vanilloid type 1 in the pathogenesis of sepsis. Hydrogen sulfide has been demonstrated to be involved in many inflammatory states including sepsis. Its contribution in neurogenic inflammation has been suggested in normal airways and urinary bladder. However, whether endogenous hydrogen sulfide would induce transient receptor potential vanilloid type 1-mediated neurogenic inflammation in sepsis remains unknown.
Prospective, experimental study.
Research laboratory.
Male Swiss mice.
Mice were subjected to cecal ligation and puncture-induced sepsis and treated with transient receptor potential vanilloid type 1 antagonist capsazepine (15 mg/kg subcutaneous) 30 mins before cecal ligation and puncture. To investigate hydrogen sulfide-mediated neurogenic inflammation in sepsis, DL-propargylglycine (50 mg/kg intraperitoneal), an inhibitor of hydrogen sulfide formation was administrated 1 hr before or 1 hr after the induction of sepsis, whereas sodium hydrosulfide (10 mg/kg intraperitoneal), a hydrogen sulfide donor, was given at the same time as cecal ligation and puncture. Lung and liver myeloperoxidase activities, liver cystathionine-gamma-lyase activity, plasma hydrogen sulfide level, histopathological examination, and survival studies were determined after induction of sepsis.
Capsazepine treatment attenuates significantly systemic inflammation and multiple organ damage caused by sepsis, and protects against sepsis-induced mortality. Similarly, administration of sodium hydrosulfide exacerbates but capsazepine reverses these deleterious effects. In the presence of DL-propargylglycine, capsazepine causes no significant changes to the attenuation of sepsis-associated systemic inflammation, multiple organ damage, and mortality. In addition, capsazepine has no effect on endogenous generation of hydrogen sulfide, suggesting that hydrogen sulfide is located upstream of transient receptor potential vanilloid type 1 activation, and may play a critical role in regulating the production and release of sensory neuropeptides in sepsis.
The present study shows that hydrogen sulfide induces systemic inflammation and multiple organ damage characteristic of sepsis via transient receptor potential vanilloid type 1-mediated neurogenic inflammation.
研究硫化氢与香草素瞬时受体型 1（TRPV1）在脓毒症发病机制中的相互作用和参与。硫化氢已被证明参与多种炎症状态，包括脓毒症。其在正常气道和膀胱中的神经原性炎症中的作用已被提出。然而，内源性硫化氢是否会在脓毒症中诱导 TRPV1 介导的神经原性炎症仍不清楚。
前瞻性、实验研究。
研究实验室。
雄性瑞士小鼠。
小鼠接受盲肠结扎和穿刺诱导的脓毒症，并在盲肠结扎和穿刺前 30 分钟用 TRPV1 拮抗剂辣椒素（15mg/kg 皮下）处理。为了研究脓毒症中硫化氢介导的神经原性炎症，在诱导脓毒症前 1 小时或后 1 小时给予硫化氢形成抑制剂 DL-丙炔基甘氨酸（50mg/kg 腹腔内），而给予硫化氢供体硫氢化钠（10mg/kg 腹腔内）与盲肠结扎和穿刺同时进行。脓毒症诱导后测定肺和肝髓过氧化物酶活性、肝胱硫醚-γ-裂解酶活性、血浆硫化氢水平、组织病理学检查和生存研究。
辣椒素治疗显著减轻脓毒症引起的全身炎症和多器官损伤，并能预防脓毒症引起的死亡。同样，给予硫氢化钠可加重但辣椒素可逆转这些有害作用。在 DL-丙炔基甘氨酸存在的情况下，辣椒素对减轻与脓毒症相关的全身炎症、多器官损伤和死亡率没有显著影响。此外，辣椒素对内源性硫化氢的产生没有影响，表明硫化氢位于 TRPV1 激活的上游，可能在调节脓毒症中感觉神经肽的产生和释放中起关键作用。
本研究表明，硫化氢通过 TRPV1 介导的神经原性炎症诱导脓毒症中具有全身炎症和多器官损伤特征的系统炎症和多器官损伤。
