Analysis of reactive oxygen species, NO, CO and H_2S as therapeutic targets in the immune complex diseases

为探讨H_2S在IC所致疾病中的作用，以NaHS为H_2S供体，进行反向被动皮肤Arthes反应。此外，我们还利用选择素缺陷小鼠(选择素-/-&gt；)进行了类似的实验，以确定选择素分子参与了H_2S介导的途径。外源性应用H_2S可显著减轻野生型(WT)小鼠与Arthes反应相关的炎症反应。也就是说，与未治疗的小鼠相比，NaHS治疗的WT小鼠皮损中肿瘤坏死因子-α、干扰素-γ的基因表达和中性粒细胞数量显著减少。NaHS治疗显著降低了E-和P-选择素小鼠皮损的这三个参数，但对L-选择素小鼠皮损皮肤的这三个参数没有影响。用注射抗E-、P-和L选择素的单抗的WT小鼠进行的阻断研究也得到了非常相似的结果。我们的结果表明，外源性应用H_2S可通过L-选择素途径，而不是通过E-或P-选择素途径，减轻逆行被动Arthes反应中的炎症反应。

To assess the roles of H_2S in the IC induced diseases, reverse passive cutaneous Arthus reaction was conducted using NaHS as an H_2S donor. Furthermore, we conducted similar experiments using selectin-deficient (selectin^<-/->) mice to determine the involvement of selectin molecules in the H_2S mediated pathway. Exogenous application of H_2S dramatically attenuated inflammatory reactions in wild type (WT) mice associated with Arthus reaction. Namely, mRNA expressions of tumor necrosis factor-α, interferon-γ and neutrophil numbers were significantly reduced in the lesional skins of NaHS treated WT mice relative to untreated ones. NaHS treatment significantly reduced these three parameters in the lesional skins of E- and P-selectin^<-/-> mice, but not in those of L- selectin^<-/-> mice. Quite similar results were obtained in the blocking study using WT mice injected with monoclonal antibodies to E-, P- and L-selectin. Our results indicated that exogenous application of H_2S attenuates inflammatory responses in reverse passive Arthus reaction through L-selectin involved pathways, but not through E- or P-selectin pathways.