血红素氧合酶1(heme oxygenase-1,Ho-1)血红素降解限速酶发热、休克、氧化应激状态>MPS微粒体产生HO11血红素分解加强>CO、胆绿素、游离铁抗调亡、抗炎、抗氧化、改善微循环、免疫负调节→组织保护血红素H0-1V胆绿素Fe2+CO免疫负调节
血红素氧合酶1(heme oxygenase-1,HO-1)血红素降解限速酶 发热、休克、氧化应激状态 MPS微粒体产生HO1↑ 血红素分解加强 CO、胆绿素、游离铁 抗凋亡、抗炎、抗氧化、改善微循环、免疫负调节 组织保护 HO-1 Fe2+ CO 胆绿素 血红素 免疫负调节
AspirinNOIL-10Alcohol15-PGJRapamycinSimvastatinCO的免疫负调节效应MHeatShockCO淋巴细胞黏附分子表达!*Proteins?淋巴细胞趋化因子表达!*淋巴细胞归巢、浸润HO-1*淋巴细胞活化、增殖*Th1型CK Th2型CK ↑*Treg ↑*中性粒细胞、MΦ炎性应答1*DC/MΦ致炎作用+DC成熟* HMGB1、TNF-α 、IL-2 BiliverdinFe++COIL-10 ↑*iNOS和NO产生★IDO表达↑HO-1在调节炎症和免疫应答中具有重要作用,很多分子均通过HO-1及其酶解产物发挥效应,故HO-1被称为治疗的漏斗(funnel)。Heme oxygenase-1upregulationsignificantlyinhibitsTNF-alphaandHmgb1 releasing and attenuateslipopolysaccharide-induced acute lunginjuryinmice[J].IntImmunopharcol,2008,8:792-798
CO的免疫负调节效应 * 淋巴细胞黏附分子表达↓ * 淋巴细胞趋化因子表达↓ * 淋巴细胞归巢、浸润↓ * 淋巴细胞活化、增殖↓ * Th1型CK↓Th2型CK↑ * Treg↑ * 中性粒细胞、MΦ炎性应答↓ * DC/Mφ致炎作用↓DC成熟↓ * HMGB1、TNF-α、IL-2↓ IL-10↑ * iNOS和NO产生↓IDO表达↑ Heme oxygenase-1 upregulation significantly inhibits TNF-alpha and Hmgb1 releasing and attenuates lipopolysaccharide-induced acute lung injury in mice[J]. Int Immunopharcol, 2008,8: 792-798 HO-1在调节炎症和免疫应答中具有重要作用 ,很多分子均通过HO-1及其酶解产物发挥效 应,故HO-1被称为治疗的漏斗(funnel)
Heme oxygenase-l upregulation significantly inhibits Hmgbl releasingand attenuates LPS-induced acute lung injury in miceAB182006h1618012h(Iw/Bu)14160B24h12140s12010100.080080420C0LPSLPS+CoPPIXLPS+ZIPPIXLPSComolLPS+CoPPXLPS+ZnPPXLPSCoPP(HO-1诱导剂)naiveZnPP(HO-1持抗剂CoPP一→诱导HO-1表达→抑制HMGB1释放→减轻LPS所致肺损伤
Heme oxygenase-1 upregulation significantly inhibits Hmgb1 releasing and attenuates LPS-induced acute lung injury in mice naive LPS CoPP(HO-1诱导剂) ZnPP(HO-1拮抗剂) CoPP诱导HO-1表达抑制HMGB1释放减轻LPS所致肺损伤