CAJ | 학술논문

目的探讨重组白细胞介素-10(rIL-10)/Fc融合蛋白对内毒素诱导的急性肺损伤(ALl)小鼠炎症调控作用及其机制.方法向气管内注射脂多糖(LPS)制成ALl动物模型;rIL-10/Fc融合蛋白采用腹腔内给药方式.132只小鼠被随机均分为正常对照组、rIL-10/Fc对照组、ALl模型组、rIL-10/Fc治疗组.每组选择25只小鼠观察24 h存活率;其余用于检测支气管肺泡灌洗液(BALF)中自细胞数量,肿瘤坏死因子-a(TNF-a)和IL-1β水平,以及肺组织髓过氧化物酶(MPO)活性、肺组织湿/干重(W/D)比值;光镜下观察肺组织病理学改变.结果注射LPS后4 h可引起BALF中TNF-a和IL-1β显著升高(P均＜0.01),rIL-10/Fc治疗组较ALI模型组有所降低,但差异无统计学意义;但在8 h和12 h,rIL-10/Fc融合蛋白能显著抑制BALF中TNF-a产生,在12 h抑制IL-1β产生;并明显改善LPS注射24 h后实验动物的存活率(P＜0.01).rIL-10/Fc对LPS诱导的ALI小鼠BALF中白细胞数量、肺组织MPO活性、肺组织W/D比值无显著改变.注射LPS 24 h后,肺组织出现了明显的炎性改变,但在rlL-10/Fc融合蛋白干预后没有出现显著的差异.结论 rIL-10/Fc融合蛋白能显著抑制LPS诱导的ALI小鼠肺促炎细胞因子产生,改善预后.
목적 탐토중조백세포개소-10(rIL-10)/Fc융합단백대내독소유도적급성폐손상(ALl)소서염증조공작용급기궤제.방법 향기관내주사지다당(LPS)제성ALl동물모형;rIL-10/Fc융합단백채용복강내급약방식.132지소서피수궤균분위정상대조조、rIL-10/Fc대조조、ALl모형조、rIL-10/Fc치료조.매조선택25지소서관찰24 h존활솔;기여용우검측지기관폐포관세액(BALF)중자세포수량,종류배사인자-a(TNF-a)화IL-1β수평,이급폐조직수과양화물매(MPO)활성、폐조직습/간중(W/D)비치;광경하관찰폐조직병이학개변.결과 주사LPS후4 h가인기BALF중TNF-a화IL-1β현저승고(P균＜0.01),rIL-10/Fc치료조교ALI모형조유소강저,단차이무통계학의의;단재8 h화12 h,rIL-10/Fc융합단백능현저억제BALF중TNF-a산생,재12 h억제IL-1β산생;병명현개선LPS주사24 h후실험동물적존활솔(P＜0.01).rIL-10/Fc대LPS유도적ALI소서BALF중백세포수량、폐조직MPO활성、폐조직W/D비치무현저개변.주사LPS 24 h후,폐조직출현료명현적염성개변,단재rlL-10/Fc융합단백간예후몰유출현현저적차이.결론 rIL-10/Fc융합단백능현저억제LPS유도적ALI소서폐촉염세포인자산생,개선예후.
Objective To clarify the regulatory role and mechanism of recombinant interleukin-10/Fc (rIL-10/Fc)fusion protein on inflammatory parameters during development of acute lung injury(ALI)induced by lipopoIysaccharide(LPS)in a murine model.Methods An ALI model was reproduced by intra-tracheal injection of LPS.rlL-10/Fc was administered intraperitonealy.One hundred and thirty-two BALB/c mice were divided into four groups,including saline control group,rlL-10/Fc control group,ALI model group,and rIL-10/Fc treatment group.Twenty-four-hour survival rate was determined in 25 mice of each group.The number of inflammatory cells and inflammatory mediators in bronchia-alveolar lavage fluid (BALF),tumor necrosis factor-a(TNF-a)and IL-1β,and also lung myeloperoxidase(MPO)activity,lung wet/dry(W/D)ratio were determined in the rest of mice.Pathological changes in lung were examined with hematoxylin-eosin(HE)staining,and inflammatory change was evaluated under microscope.Results Levels of TNF-a and IL-1β in BALF were substantially increased 4 hours after intra-tracheal LPS(both P＜0.01),and they were lowered but without significant difference after rIL-10/Fc administration.However,rlL-10/Fc fusion protein markedly attenuated release of TNF-a at 8 hours and 12 hours,and IL-1β was lowered at 12 hours after LPS challenge.Pre-treatment with rlL-10/Fc fusion protein significantly improved survival rate at 24 hours in LPS challenged mice(P＜0.01).There was no significant difference in cell count in BALF,MPO,lung W/D ratio,after treatment of rlL-10/Fc fusion protein.Obvious inflammatory changes were found in lung was found pathologically at 24 hours after LPS injection,but there was no significant difference compared with ALI mice with rIL-10/Fc fusion protein administration.Conclusion rIL-10/Fc fusion protein inhibits release of TNF-a and IL-1β in BALF in a LPS-induced ALI murine model.rIL-10/Fc fusion protein improves survival rate in ALI mice by decreasing the release of pro-inflammatory cytokines.