Andruski Benjamin, McCafferty Donna-Marie, Ignacy Teegan, Millen Brandie, McDougall Jason J
Dept. of Physiology and Biophysics, Univ. of Calgary, 3330 Hospital Dr. NW, Calgary, Alberta T2N 4N1, Canada.
Am J Physiol Regul Integr Comp Physiol. 2008 Sep;295(3):R814-20. doi: 10.1152/ajpregu.90524.2008. Epub 2008 Jul 30.
Hydrogen sulfide (H(2)S) is an endogenous gaseous mediator with the ability to modulate tissue inflammation and pain. The aim of this study was to determine the effect of an H(2)S donor (Na(2)S) on leukocyte-endothelium interactions, blood flow, and pain sensation in acutely inflamed knee joints. Acute arthritis was induced in urethane anesthetized C57bl/6 mice by intra-articular injection of kaolin/carrageenan (24-h recovery), and the effect of local administration of Na(2)S on leukocyte trafficking was measured by intravital microscopy. Synovial blood flow was measured in inflamed knees by laser Doppler perfusion imaging. Finally, the effect of an intra-articular injection of Na(2)S on joint pain in control and inflamed rats was determined by hindlimb incapacitance and von Frey hair algesiometry. Local administration of an H(2)S donor to inflamed knees caused a dose-dependent reduction in leukocyte adherence and an increase in leukocyte velocity. These effects could be inhibited by coadministration of the ATP-sensitive K(+) channel blocker glibenclamide. Local administration of Na(2)S to inflamed joints caused a pronounced vasoconstrictor response; however, there was no observable effect of Na(2)S on joint pain. These findings establish H(2)S as a novel signaling molecule in rodent knee joints. H(2)S exhibits potent anti-inflammatory properties, but with no detectable effect on joint pain.
硫化氢（H₂S）是一种内源性气体介质，具有调节组织炎症和疼痛的能力。本研究旨在确定硫化氢供体（硫化钠）对急性炎症膝关节中白细胞与内皮细胞相互作用、血流及痛觉的影响。通过向乌拉坦麻醉的C57bl/6小鼠关节内注射高岭土/角叉菜胶诱导急性关节炎（恢复24小时），并通过活体显微镜观察测量局部给予硫化钠对白细胞运输的影响。通过激光多普勒灌注成像测量炎症膝关节的滑膜血流。最后，通过后肢失能和von Frey毛发触觉测量法确定关节内注射硫化钠对对照和炎症大鼠关节疼痛的影响。向炎症膝关节局部给予硫化氢供体导致白细胞黏附呈剂量依赖性降低，白细胞速度增加。这些效应可被ATP敏感性钾通道阻滞剂格列本脲共同给药所抑制。向炎症关节局部给予硫化钠引起明显的血管收缩反应；然而，硫化钠对关节疼痛没有可观察到的影响。这些发现确立了硫化氢作为啮齿动物膝关节中的一种新型信号分子。硫化氢具有强大的抗炎特性，但对关节疼痛没有可检测到的影响。
