Cardiovascular Biology Research Group, Department of Pharmacology, Yong Loo Lin School of Medicine, CRC MD11, National University of Singapore 117597, Singapore, Singapore.
J Inflamm (Lond). 2009 Dec 30;6:35. doi: 10.1186/1476-9255-6-35.
Hydrogen sulfide (H(2)S), a gaseous mediator plays an important role in a wide range of physiological and pathological processes. H(2)S has been extensively studied for its various roles in cardiovascular and neurological disorders. However, the role of H(2)S in inflammation is still controversial. The current study was aimed to investigate the therapeutic potential of sodium hydrosulfide (NaHS), an H(2)S donor in in vivo model of acute pancreatitis in mice.
Acute pancreatitis was induced in mice by hourly caerulein injections (50 mug/kg) for 10 hours. Mice were treated with different dosages of NaHS (5 mg/kg, 10 mg/kg or 15 mg/kg) or with vehicle, distilled water (DW). NaHS or DW was administered 1 h before induction of pancreatitis. Mice were sacrificed 1 h after the last caerulein injection. Blood, pancreas and lung tissues were collected and were processed to measure the plasma amylase, myeloperoxidase (MPO) activities in pancreas and lung and chemokines and adhesion molecules in pancreas and lung.
It was revealed that significant reduction of inflammation, both in pancreas and lung was associated with NaHS 10 mg/kg. Further the anti-inflammatory effects of NaHS 10 mg/kg were associated with reduction of pancreatic and pulmonary inflammatory chemokines and adhesion molecules. NaHS 5 mg/kg did not cause significant improvement on inflammation in pancreas and associated lung injury and NaHS 15 mg/kg did not further enhance the beneficial effects seen with NaHS 10 mg/kg.
In conclusion, these data provide evidence for anti-inflammatory effects of H(2)S based on its dosage used.
硫化氢(H₂S)作为一种气态介质,在广泛的生理和病理过程中发挥着重要作用。H₂S 因其在心血管和神经紊乱中的各种作用而得到广泛研究。然而,H₂S 在炎症中的作用仍存在争议。本研究旨在探讨 H₂S 供体硫氢化钠(NaHS)在小鼠急性胰腺炎体内模型中的治疗潜力。
通过每小时注射(50μg/kg) 10 小时的斑蝥素诱导小鼠急性胰腺炎。用不同剂量的 NaHS(5mg/kg、10mg/kg 或 15mg/kg)或载体、蒸馏水(DW)处理小鼠。NaHS 或 DW 在胰腺炎诱导前 1 小时给药。在最后一次斑蝥素注射后 1 小时处死小鼠。收集血液、胰腺和肺组织,并进行处理以测量血浆淀粉酶、胰腺和肺髓过氧化物酶(MPO)活性以及胰腺和肺中的趋化因子和粘附分子。
结果表明,与 10mg/kg 的 NaHS 相比,炎症在胰腺和肺中均显著减少。进一步研究发现,10mg/kg 的 NaHS 的抗炎作用与胰腺和肺中炎症趋化因子和粘附分子的减少有关。5mg/kg 的 NaHS 对胰腺炎症和相关的肺损伤没有显著改善作用,而 15mg/kg 的 NaHS 并没有进一步增强 10mg/kg 的 NaHS 的有益作用。
综上所述,这些数据为 H₂S 的抗炎作用提供了证据,其依据是所用剂量。