Background Protectin D1 （PD1）,derived from docosahexaenoic acid,has been shown to control and resolve inflammation in some experimental models of inflammatory disorders.We investigated the protective roles of protec...Background Protectin D1 （PD1）,derived from docosahexaenoic acid,has been shown to control and resolve inflammation in some experimental models of inflammatory disorders.We investigated the protective roles of protectin D1 in pulmonary inflammation and lung injury induced by lipopolysaccharide （LPS）.Methods Mice were randomly assigned to six groups （n=6 per group）：sham-vehicle group,sham-PD1 group,shamzVAD-fmk group,LPS-vehicle group,LPS-PD1 group,and LPS-PD1-zVAD-fmk group.Mice were injected intratracheally with 3 mg/kg LPS or saline,followed 24 hours later by intravenous injection of 200 μg/mouse PD1 or vehicle.At the same time,some mice were also injected intraperitoneally with the pan-caspase inhibitor zVAD-fmk.Seventy-two hours after LPS challenge,samples of pulmonary tissue and bronchoalveolar lavage fluid were collected.Optical microscopy was used to examine pathological changes in lungs.Cellularity and protein concentration in bronchoalveolar lavage fluid were analyzed.Lung wet/dry ratios and myeloperoxidase activity were measured.Apoptosis of neutrophils in bronchoalveolar lavage fluid （BALF） was also evaluated by flow cytometry.Results Intratracheal instillation of LPS increased neutrophil counts,protein concentration in bronchoalveolar lavage fluid and myeloperoxidase activity,it induced lung histological injury and edema,and also suppressed apoptosis of neutrophils in BALF.Posttreatment with PD1 inhibited LPS-evoked changes in BALF neutrophil counts and protein concentration and lung myeloperoxidase activity,with the outcome of decreased pulmonary edema and histological injury.In addition,PD1 promoted apoptosis of neutrophils in BALF.The beneficial effects of PD1 were blocked by zVAD-fmk.Conclusion Posttreatment with PD1 enhances resolution of lung inflammation during LPS-induced acute lung injury by enhancing apoptosis in emigrated neutrophils,which is,at least in part,caspase-dependent.展开更多
Background：Acute lung injury （ALI） is a severe disease with high mortality and poor prognosis.Protectin DX （PDX）,a pro-resolving lipid mediator,exhibits protective effects in ALI.Our experiment aimed to explore t...Background：Acute lung injury （ALI） is a severe disease with high mortality and poor prognosis.Protectin DX （PDX）,a pro-resolving lipid mediator,exhibits protective effects in ALI.Our experiment aimed to explore the effects and related mechanisms of PDX in mice with ALI induced by lipopolysaccharide （LPS）.Methods：BALB/c mice were randomly divided into five groups：sham,LPS,LPS plus 1 ng ofPDX （LPS ＋ PDX-1 ng）,LPS plus 10 ng ofPDX （LPS ＋ PDX-10 ng）,and LPS plus 100 ng ofPDX （LPS ＋ PDX-100 ng）.Bronchoalveolar lavage fluids （BALFs） were collected after 24 h,and total cells,polymorphonuclear leukocytes,monocyte-macrophages,and lymphocytes in BALF were enumerated.The concentration of interleukin （IL）-1 β3,IL-6,IL-10,tumor necrosis factor-alpha （TNF-α）,macrophage inflammatory protein （MIP）-1 cα,and MIP-2 in BALF was determined,and histopathological changes of the lung were observed.The concentration of protein in BALF and lung wet/dry weight ratios were detected to evaluate pulmonary edema.After determining the optimal dose of PDX,neutrophil-platelet interactions in whole blood were evaluated by flow cytometry.Results：The highest dose of PDX （100 ng/mouse） failed to provide pulmonary protective effects,whereas lower doses of PDX （1 ng/mouse and 10 ng/mouse）,especially 1 ng PDX,alleviated pulmonary histopathological changes,mitigated LPS-induced ALI and pulmonary edema,inhibited neutrophil infiltration,and reduced pro-inflammatory mediator （IL-1β,IL-6,TNF-α,and MIP-lα） levels.Meanwhile,1 ng PDX exhibited pro-resolving functions in ALI including upregulation of monocyte-macrophage numbers and anti-inflammatory mediator IL-l 0 levels.The flow cytometry results showed that PDX could inhibit neutrophil-platelet interactions in ALI.Conclusion：PDX exerts protective effects in LPS-inducedALI by mitigating pulmonary inflammation and abrogating neutrophil-platelet interactions.展开更多
目的:研究保护素D1,一种鱼油的代谢产物,对重症急性胰腺炎(SAP)小鼠肠粘膜损伤的保护作用。方法:将雄性25~30 g ICR小鼠随机分为假手术组(Sham组,行开腹关腹假手术操作)、重症胰腺炎模型组(SAP组,开腹胰管结扎建立SAP模型)和保护素D1治...目的:研究保护素D1,一种鱼油的代谢产物,对重症急性胰腺炎(SAP)小鼠肠粘膜损伤的保护作用。方法:将雄性25~30 g ICR小鼠随机分为假手术组(Sham组,行开腹关腹假手术操作)、重症胰腺炎模型组(SAP组,开腹胰管结扎建立SAP模型)和保护素D1治疗组(SAP+protectin D1组,SAP造模1 h后经眼内眦注射保护素D1,2 ng/只),每组12只,造模后24 h取材进行肠道组织病理检测及评分;免疫荧光法检测细胞凋亡、肠道上皮紧密连接蛋白闭锁小带蛋白-1(ZO-1)和Occludin表达;免疫组织化学方法检测细胞凋亡关键蛋白Caspase3表达。结果:与SAP组相比,保护素D1治疗组小鼠肠道病理损伤显著减轻。SAP组小鼠肠道上皮细胞凋亡显著增加,保护素D1治疗后肠道上皮细胞凋亡减轻,Caspase3表达下降,差异有统计学意义(P<0.01)。荧光染色检测显示,与假手术组相比,SAP模型组小鼠肠道Occludin表达显著下降,保护素D1治疗组较SAP模型组表达上升(P<0.01);SAP组小鼠肠道ZO-1表达显著下降,保护素D1治疗组较SAP组表达上升(P<0.05)。结论:保护素D1对SAP模型小鼠肠道粘膜具有保护作用,有望为SAP肠粘膜屏障功能损害提供新的治疗方法。展开更多
基金the Natural Science Foundation of Zhejing Province,China
文摘Background Protectin D1 （PD1）,derived from docosahexaenoic acid,has been shown to control and resolve inflammation in some experimental models of inflammatory disorders.We investigated the protective roles of protectin D1 in pulmonary inflammation and lung injury induced by lipopolysaccharide （LPS）.Methods Mice were randomly assigned to six groups （n=6 per group）：sham-vehicle group,sham-PD1 group,shamzVAD-fmk group,LPS-vehicle group,LPS-PD1 group,and LPS-PD1-zVAD-fmk group.Mice were injected intratracheally with 3 mg/kg LPS or saline,followed 24 hours later by intravenous injection of 200 μg/mouse PD1 or vehicle.At the same time,some mice were also injected intraperitoneally with the pan-caspase inhibitor zVAD-fmk.Seventy-two hours after LPS challenge,samples of pulmonary tissue and bronchoalveolar lavage fluid were collected.Optical microscopy was used to examine pathological changes in lungs.Cellularity and protein concentration in bronchoalveolar lavage fluid were analyzed.Lung wet/dry ratios and myeloperoxidase activity were measured.Apoptosis of neutrophils in bronchoalveolar lavage fluid （BALF） was also evaluated by flow cytometry.Results Intratracheal instillation of LPS increased neutrophil counts,protein concentration in bronchoalveolar lavage fluid and myeloperoxidase activity,it induced lung histological injury and edema,and also suppressed apoptosis of neutrophils in BALF.Posttreatment with PD1 inhibited LPS-evoked changes in BALF neutrophil counts and protein concentration and lung myeloperoxidase activity,with the outcome of decreased pulmonary edema and histological injury.In addition,PD1 promoted apoptosis of neutrophils in BALF.The beneficial effects of PD1 were blocked by zVAD-fmk.Conclusion Posttreatment with PD1 enhances resolution of lung inflammation during LPS-induced acute lung injury by enhancing apoptosis in emigrated neutrophils,which is,at least in part,caspase-dependent.
基金This work was supported by National Natural Science Foundation of China （No. 82372036,81671890）.
文摘Background：Acute lung injury （ALI） is a severe disease with high mortality and poor prognosis.Protectin DX （PDX）,a pro-resolving lipid mediator,exhibits protective effects in ALI.Our experiment aimed to explore the effects and related mechanisms of PDX in mice with ALI induced by lipopolysaccharide （LPS）.Methods：BALB/c mice were randomly divided into five groups：sham,LPS,LPS plus 1 ng ofPDX （LPS ＋ PDX-1 ng）,LPS plus 10 ng ofPDX （LPS ＋ PDX-10 ng）,and LPS plus 100 ng ofPDX （LPS ＋ PDX-100 ng）.Bronchoalveolar lavage fluids （BALFs） were collected after 24 h,and total cells,polymorphonuclear leukocytes,monocyte-macrophages,and lymphocytes in BALF were enumerated.The concentration of interleukin （IL）-1 β3,IL-6,IL-10,tumor necrosis factor-alpha （TNF-α）,macrophage inflammatory protein （MIP）-1 cα,and MIP-2 in BALF was determined,and histopathological changes of the lung were observed.The concentration of protein in BALF and lung wet/dry weight ratios were detected to evaluate pulmonary edema.After determining the optimal dose of PDX,neutrophil-platelet interactions in whole blood were evaluated by flow cytometry.Results：The highest dose of PDX （100 ng/mouse） failed to provide pulmonary protective effects,whereas lower doses of PDX （1 ng/mouse and 10 ng/mouse）,especially 1 ng PDX,alleviated pulmonary histopathological changes,mitigated LPS-induced ALI and pulmonary edema,inhibited neutrophil infiltration,and reduced pro-inflammatory mediator （IL-1β,IL-6,TNF-α,and MIP-lα） levels.Meanwhile,1 ng PDX exhibited pro-resolving functions in ALI including upregulation of monocyte-macrophage numbers and anti-inflammatory mediator IL-l 0 levels.The flow cytometry results showed that PDX could inhibit neutrophil-platelet interactions in ALI.Conclusion：PDX exerts protective effects in LPS-inducedALI by mitigating pulmonary inflammation and abrogating neutrophil-platelet interactions.
