摘要
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 myeloidcells，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PQ80mg／kg一次性灌胃后2h，单抗组腹腔注射抗TREM-1mAb（250Ixg／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1mg／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、48h肺组织中核转录因子（NF）-KB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）-0l、白细胞介素（IL）．10、可溶性TREM（sTREM）．1和TREM一1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，LPl7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．d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，48h时明显高于染毒组，单抗组TREM-148h明显高于染毒组，差异均有统计学意义（P〈0．05），6hLP17组TNF．d、TREM-1水平较染毒组升高，差异均有统计学意义（P〈0．05）。24h染毒组血清中TNF．d、IL．10达高峰与对照组比较差异明显，48h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、48hLP17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，48h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-KB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。
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 anti- TREM - 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-KB in lung tissue was determined by immunohistochemistry.The levels of TNF-α, 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-KB 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 downregulated the expressions of NF-κB and proinflammatory eytokines, while led to a slight increase of anti-inflammatory cytokines and a decline of lung pathology injury score. Coneluslon TREM-1 may involve in inflammatory response by promoting the generation of inflammatory factors via NF-KB pathway, thus lead to lung pathological changes.
出处
《中华劳动卫生职业病杂志》
CAS
CSCD
2015年第9期646-651,共6页
Chinese Journal of Industrial Hygiene and Occupational Diseases
关键词
髓系细胞触发受体-1
百草枯
急性肺损伤
Triggering receptor- 1 expressed on myeloid cells
Paraquat
Acute lung injury
