中华劳动卫生职业病杂志
中華勞動衛生職業病雜誌
중화노동위생직업병잡지
Chinese Journal of Industrial Hygiene and Occupational Diseases
2015年
9期
646-651
,共6页
魏明%涂玲%梁颖红%刘佳%龚艳杰%肖笛鸣%张宜花
魏明%塗玲%樑穎紅%劉佳%龔豔傑%肖笛鳴%張宜花
위명%도령%량영홍%류가%공염걸%초적명%장의화
髓系细胞触发受体-1%百草枯%急性肺损伤
髓繫細胞觸髮受體-1%百草枯%急性肺損傷
수계세포촉발수체-1%백초고%급성폐손상
Triggering receptor-1 expressed on myeloid cells%Paraquat%Acute lung injury
目的 观察特异性激活或阻断髓系细胞触发受体1(triggering receptor-1 expressed on myeloid cells,TREM-1)在急性百草枯(PQ)中毒致SD大鼠肺损伤中的变化,探讨其在PQ致肺损伤中的作用.方法 80只SD大鼠随机分为生理盐水对照组、PQ染毒组、抗TREM-1单克隆抗体(单抗)组和LP17人工合成肽(LP17)组,每组20只.染毒组、单抗组和LP17组给予生理盐水稀释PQ 80 mg/kg一次性灌胃后2h,单抗组腹腔注射抗TREM-1 mAb(250 μg/kg),LP17组尾静脉注射LP17人工合成肽(3.5mg/kg),染毒组给予等量生理盐水腹腔注射,对照组给予生理盐水1 mg/kg灌胃后2h后,给予等量生理盐水腹腔注射.采用免疫组化法测定各组6、12、24、48 h肺组织中核转录因子(NF)-κB活性的表达;采用酶联免疫吸附法(ELISA)测定各时点血清及肺组织匀浆中肿瘤坏死因子(TNF)-α、白细胞介素(IL)-10、可溶性TREM(sTREM)-1和TREM-1的含量;观察各组各时点肺组织形态学改变,比较肺组织病理损伤评分.结果 染毒组肺匀浆12h时p65活化程度高于单抗组,LP17组12h时p65的活化程度明显低于染毒组,差异有统计学意义(P＜0.05).单抗组肺匀浆中TNF-α时点均维持在较高水平,6h时高于染毒组,各时点IL-10也均在较高水平,48 h时明显高于染毒组,单抗组TREM-1 48 h明显高于染毒组,差异均有统计学意义(P＜0.05),6 h LP17组TNF-α、TREM-1水平较染毒组升高,差异均有统计学意义(P＜0.05).24 h染毒组血清中TNF-α、1L-10达高峰与对照组比较差异明显,48 h单抗组sTREM-1明显高于染毒组,差异均有统计学意义(P＜0.05),12、24、48 h LP17组TNF-α、sTREM-1水平比同时点染毒组低,且整体水平呈下降趋势,6h单抗组IL-10水平较染毒组高,12h时下降到最低值,后缓慢上升,48 h时IL-10水平高于染毒组,差异均有统计学意义(P＜0.05).结论 TREM-1表达可通过NF-κB激活途径促进炎症因子的生成,启动炎症反应,导致染毒SD大鼠的肺部病理损伤.
目的 觀察特異性激活或阻斷髓繫細胞觸髮受體1(triggering receptor-1 expressed on myeloid cells,TREM-1)在急性百草枯(PQ)中毒緻SD大鼠肺損傷中的變化,探討其在PQ緻肺損傷中的作用.方法 80隻SD大鼠隨機分為生理鹽水對照組、PQ染毒組、抗TREM-1單剋隆抗體(單抗)組和LP17人工閤成肽(LP17)組,每組20隻.染毒組、單抗組和LP17組給予生理鹽水稀釋PQ 80 mg/kg一次性灌胃後2h,單抗組腹腔註射抗TREM-1 mAb(250 μg/kg),LP17組尾靜脈註射LP17人工閤成肽(3.5mg/kg),染毒組給予等量生理鹽水腹腔註射,對照組給予生理鹽水1 mg/kg灌胃後2h後,給予等量生理鹽水腹腔註射.採用免疫組化法測定各組6、12、24、48 h肺組織中覈轉錄因子(NF)-κB活性的錶達;採用酶聯免疫吸附法(ELISA)測定各時點血清及肺組織勻漿中腫瘤壞死因子(TNF)-α、白細胞介素(IL)-10、可溶性TREM(sTREM)-1和TREM-1的含量;觀察各組各時點肺組織形態學改變,比較肺組織病理損傷評分.結果 染毒組肺勻漿12h時p65活化程度高于單抗組,LP17組12h時p65的活化程度明顯低于染毒組,差異有統計學意義(P＜0.05).單抗組肺勻漿中TNF-α時點均維持在較高水平,6h時高于染毒組,各時點IL-10也均在較高水平,48 h時明顯高于染毒組,單抗組TREM-1 48 h明顯高于染毒組,差異均有統計學意義(P＜0.05),6 h LP17組TNF-α、TREM-1水平較染毒組升高,差異均有統計學意義(P＜0.05).24 h染毒組血清中TNF-α、1L-10達高峰與對照組比較差異明顯,48 h單抗組sTREM-1明顯高于染毒組,差異均有統計學意義(P＜0.05),12、24、48 h LP17組TNF-α、sTREM-1水平比同時點染毒組低,且整體水平呈下降趨勢,6h單抗組IL-10水平較染毒組高,12h時下降到最低值,後緩慢上升,48 h時IL-10水平高于染毒組,差異均有統計學意義(P＜0.05).結論 TREM-1錶達可通過NF-κB激活途徑促進炎癥因子的生成,啟動炎癥反應,導緻染毒SD大鼠的肺部病理損傷.
목적 관찰특이성격활혹조단수계세포촉발수체1(triggering receptor-1 expressed on myeloid cells,TREM-1)재급성백초고(PQ)중독치SD대서폐손상중적변화,탐토기재PQ치폐손상중적작용.방법 80지SD대서수궤분위생리염수대조조、PQ염독조、항TREM-1단극륭항체(단항)조화LP17인공합성태(LP17)조,매조20지.염독조、단항조화LP17조급여생리염수희석PQ 80 mg/kg일차성관위후2h,단항조복강주사항TREM-1 mAb(250 μg/kg),LP17조미정맥주사LP17인공합성태(3.5mg/kg),염독조급여등량생리염수복강주사,대조조급여생리염수1 mg/kg관위후2h후,급여등량생리염수복강주사.채용면역조화법측정각조6、12、24、48 h폐조직중핵전록인자(NF)-κB활성적표체;채용매련면역흡부법(ELISA)측정각시점혈청급폐조직균장중종류배사인자(TNF)-α、백세포개소(IL)-10、가용성TREM(sTREM)-1화TREM-1적함량;관찰각조각시점폐조직형태학개변,비교폐조직병리손상평분.결과 염독조폐균장12h시p65활화정도고우단항조,LP17조12h시p65적활화정도명현저우염독조,차이유통계학의의(P＜0.05).단항조폐균장중TNF-α시점균유지재교고수평,6h시고우염독조,각시점IL-10야균재교고수평,48 h시명현고우염독조,단항조TREM-1 48 h명현고우염독조,차이균유통계학의의(P＜0.05),6 h LP17조TNF-α、TREM-1수평교염독조승고,차이균유통계학의의(P＜0.05).24 h염독조혈청중TNF-α、1L-10체고봉여대조조비교차이명현,48 h단항조sTREM-1명현고우염독조,차이균유통계학의의(P＜0.05),12、24、48 h LP17조TNF-α、sTREM-1수평비동시점염독조저,차정체수평정하강추세,6h단항조IL-10수평교염독조고,12h시하강도최저치,후완만상승,48 h시IL-10수평고우염독조,차이균유통계학의의(P＜0.05).결론 TREM-1표체가통과NF-κB격활도경촉진염증인자적생성,계동염증반응,도치염독SD대서적폐부병리손상.
Objective To investigate the transduction pathway of triggering receptor-1 expressed on myeloid cells (TREM-1) in acute lung injure induced by paraquat in rats through the activating or blocking TREM-1,to observe the effect of signal transduction pathway in the acute lung injure induced-paraquat.Methods 80 SD rats were randomly divided into normal saline control group (n=20),PQ poisoning group(n=20),antibody group (n=20),and LP17 group (n=20).poisoning group,antibody group and LP17 group were given saline diluting PQ 80 mg/kg of disposable lavage after 2 h,a single set of intraperitoneal injection of antiTREM-1 mAb (250 g/kg),tail intravenous LP17 group synthetic peptide (3.5 mg/kg),poisoning group was given equal normal saline intraperitoneal injection,control group given normal saline 1 mg/kg after 2 h after lavage,given the amount of intraperitoneal injection of saline solution.The expression of NF-κB in lung tissue was determined by immunohistochemistry.The levels of TNF-a,IL-10,TREM-1,and soluble TREM-1 (sTREM-1)in lung tissue and serum were measured by ELISA.Pathology changes of lung were observed under light microscope,and lung score of pathology was compared.Results Administration of anti-TREM-1 mAb after PQ poisoning modeling significantly increased the NF-κB expression in lung tissue at 48 h,resulting in a large number of pro-inflammatory cytokines releasing in the lung tissue and serum and lung pathology injury score increasing.Administration of LP17 after modeling significantly down-·regulated the expressions of NF-κB and proinflammatory cytokines,while led to a slight increase of anti-inflammatory cytokines and a decline of lung pathology injury score.Conclusion TREM-1 may involve in inflammatory response by promoting the generation of inflammatory factors via NF-κB pathway,thus lead to lung pathological changes.
