摘要
目的:探讨硫化氢(H_2S)在脓毒症大鼠结肠黏膜损伤中的作用。方法:雄性SD大鼠随机分为5组:对照组、脓毒症组、脓毒症+NaHS组、脓毒症+DL-炔丙基甘氨酸(PAG)组和脓毒症+氨基-羟乙酸(AOAA)组。除对照组行假手术外,其余各组采用盲肠结扎穿孔(CLP)法制作大鼠脓毒症模型,术前30 min分别腹腔注射等量生理盐水、NaHS(10 mg/kg)、PAG(50 mg/kg)、AOAA(20 mg/kg)。20 h后处死大鼠,取结肠组织,测定其H_2S、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)含量,髓过氧化物酶(MPO)活性和胱硫醚-γ-裂解酶(CSE)mRNA、胱硫醚-β-合成酶(CBS)mRNA表达水平,光学显微镜下观察结肠组织病理学变化。结果:①与对照组相比,脓毒症组结肠组织中H_2S、TNF-α、IL-1β浓度增加,MPO活性明显增强(P<0.01),CBS mRNA、CSE mRNA表达水平提高(P<0.01),其组织结构遭到破坏,炎性细胞浸润增多。②与脓毒症组相比,脓毒症+NaHS组结肠组织中H_2S、TNF-α、IL-1β浓度增加,MPO活性增强(P<0.05),CBS mRNA、CSE mRNA表达水平降低(P<0.01),结肠组织结构破坏加剧,更多炎性细胞浸润。与脓毒症组相比,脓毒症+PAG组和脓毒症+AOAA组结肠组织中H_2S、TNF-α、IL-1β浓度降低,MPO活性减弱。但脓毒症+PAG组各指标变化的差异无统计学意义,而脓毒症+AOAA组各指标的变化差异有显著性(P<0.01);两组结肠组织结构破坏减轻,炎性细胞浸润减少。结论:脓毒症时,结肠组织内主要由CBS催化产生H_2S,增多的H_2S通过增强炎症反应加重结肠黏膜损伤。
Objective： To investigate the effects of hydrogen sulfide on the injury of colon mucosa in septic rats. Methods： Male SD rats were divided into 5 groups： control group, sepsis group, sepsis＋ NariS group, sepsis＋ DL propargylglycine （PAG） group, and sepsis＋ aminooxyacetic acid （AOAA） group. Rats were subjected to cecal ligation and puncture （CLP） to induce sepsis, and respectively treated with saline intraperitoneally, NariS 10 mg/kg intraperitoneally, PAG 50 mg/kg intraperitonealIy, AOAA 20 mg/kg intraperitoneally 30 minutes before CLP, except that the rats in control group received sham operation. H2 S synthesis, the concentration of tumor necrosis factor-α（TNF-α）, interleukin-1β （IL-1β）, the activity of MPO, cystathionine-γ-lyase （CSE） mRNA level, and cystathionine 13 synthase （CBS） mRNA level in colonic tissue were determined 20 hours after CLP. The pathological changes and infiltration of inflammatory cells in colon tissue were observed. Results： （1）Compared with normal group, the H2 S synthesis, the concentration of TNF-α,IL-1β,the activity of MPO, CSE mRNA level and CBS mRNA level in colon of sepsis group were increased （P〈0.01）, the histological structurc of colon was damaged and infiltration of inflammatory cells was increased in the tissue. （2）When compared with sepsis group, the H2S synthesis, the concentration of TNF-α and IL-1β, and the activity of MPO were increased in sepsis＋ Naris group（P〈0.05）, but there was a decrease in CSE mRNA level and CBS mRNA level （P〈0.01）. The damage to the colon structure was worse than that in sepsis group. On the other hand, the administration of AOAA could significantly reduce the systemic inflammation of sepsis, as evidenced by a decrease in TNF-α,IL-1β contents and the activity of MPO （P〈0.01）and less damage to the colon structure. The H2 S synthesis, the concentration of TNF-α , IL-1β and the activity of MPO were also decreased in sepsis＋PAG group, but with no statistically s
出处
《感染．炎症．修复》
2010年第4期195-199,共5页
Infection Inflammation Repair
基金
国家自然科学基金资助项目(81071526)
关键词
硫化氢
脓毒症
结肠黏膜
损伤
Hydrogen sulfide Sepsis Colon mucosa Injury
