摘要目的:研究人脐带间充质干细胞条件培养基（CM）对宫内感染致新生大鼠肺损伤模型的影响。方法:选取孕龄20 d SD大鼠18只，随机分为3组（ n=6）。NS组孕20、21 d连续2 d腹腔注入生理盐水1 ml，所生幼鼠随机选取30只新生鼠，于第3天腹腔注射生理盐水0.1 ml。LPS组孕20、21 d连续2 d予腹腔注入LPS（大肠杆菌内毒素，2.5 mg·kg -1·d -1），随机选取30只新生鼠，于第3天腹腔注入0.1 ml生理盐水。LPS+CM组孕20、21 d连续2 d予腹腔注入LPS（2.5 mg·kg -1·d -1），所生幼鼠随机选取30只新生鼠，于第3天腹腔注入CM 0.1 ml。3组新生鼠分别于7、14、21 d随机选取10只麻醉处死，观察各组3个时间点新生鼠体质量、肺重、肺重/体质量；HE染色观察新生鼠肺形态学和鼠肺辐射状肺泡计数（RAC）；液相芯片技术检测各组新生鼠血清中IL-6、IL-10、TNF-α变化。 结果:LPS组新生鼠7、14、21 d体质量较NS组、LPS+CM组均减轻，3组新生鼠体质量随生后日龄不断增加（均 P<0.05）；LPS组新生鼠14、21 d肺重较NS组和LPS+CM组减轻，3组肺重随生后日龄不断增加（均 P<0.05）；LPS组新生鼠7 d肺重/体质量较NS组、LPS+CM组升高（均 P<0.05），14 d仅较NS组升高（ P<0.05），21 d仅较LPS+CM组降低（ P<0.05），3组新生鼠肺重/体质量随生后日龄不断下降（均 P<0.05）。肺组织HE染色显示NS组新生鼠肺组织结构完整，肺泡扩张均匀，肺泡间隔未见明显增厚，间隔内极少量炎细胞浸润，肺泡腔清晰；LPS组新生鼠肺泡数目减少，肺泡体积增大，肺泡间隔减少，部分肺泡间隔增厚，间隔内炎细胞浸润；LPS+CM组新生鼠肺泡数目、体积、肺泡间隔及间隔炎细胞浸润状态均较LPS组好转，损伤程度减轻。7 d LPS组新生鼠肺组织的RAC仅较NS组减少（ P<0.05），14、21 d较NS组、LPS+CM组均减少（均 P<0.05），3组新生鼠肺组织RAC随生后日龄不断增加（均 P<0.05）。与NS组比较，LPS组新生鼠血清IL-6在7、14、21 d升高（均 P<0.05），LPS+CM组则在7、21 d升高（均 P<0.05），LPS+CM组新生鼠血清IL-6在14、21 d较LPS组降低（均 P<0.05），3组新生鼠血清IL-6随生后日龄不断下降（均 P<0.05）。与NS组、LPS+CM组比较，LPS组新生鼠血清IL-10在7 d时降低（均 P<0.05），3组新生鼠血清IL-10随生后日龄不断下降（均 P<0.05）。LPS组血清TNF-α在7、14、21 d较NS组升高（均 P<0.05），14 d较LPS+CM组升高（ P<0.05），3组TNF-α随生后日龄不断增加（均 P<0.05）。 结论:通过孕20、21 d大鼠腹腔注射LPS能够成功构建宫内感染致新生大鼠肺损伤模型。宫内感染致新生大鼠炎症细胞因子发生变化，促炎因子表达量增加，抑炎因子表达量下降，CM干预对宫内感染致新生大鼠肺损伤具有一定保护作用。

abstractsObjective:To investigate the effect of human umbilical cord mesenchymal stem cell (hu-MSC) conditioned medium (CM) on lung injury induced by intrauterine infection in rat models.Methods:Eighteen SD rats with at 20 days of gestation were randomly divided into three groups ( n=6 each) . In the NS group, 1 ml normal saline was injected intraperitoneally for 2 consecutive days on days 20 and 21 of pregnancy; 30 of the neonatal off springs were randomly selected and injected with 0.1 ml normal saline intraperitoneally on day 3 postnatum. In the LPS group, lipopolysaccharide (an E. coli endotoxin) at a dose of 2.5 mg·kg -1·d -1 was intraperitoneally injected for 2 consecutive days on days 20 and 21 of pregnancy; 30 of the neonatal off springs were randomly selected and injected with 0.1 ml normal saline intraperitoneally on day 3 postnatum. In the LPS+CM group, LPS at a dose of 2.5 mg·kg -1·d -1 was intraperitoneally injected for 2 consecutive days on days 20 and 21 of pregnancy; 30 of the neonatal off springs were randomly selected and injected with 0.1 ml CM intraperitoneally on day 3 postnatum. The three groups of neonatal rats were randomly sacrificed in tens by anesthesia on days 7, 14, and 21. The body mass, lung weight, and lung weight/body weight of the neonatal rats of each group were examined at the three time points. HE staining was used to study the morphology and radial alveolar count (RAC) of the lung in the rats. Luminex xMAP liquid phase microarray was used to detect the changes in serum IL-6, IL-10 and TNF-α in each group of neonatal rats. Results:The body weight of neonatal rats in LPS group compared with the NS and LPS+CM groups on days 7, 14 and 21; the body weight of neonatal rats in three groups increased with days after birth (all P< 0.05) . The lung weight of neonatal rats in LPS group was lower compared with NS and LPS+ CM groups on days 14 and 21; the lung weight of neonatal rats in three groups increased with days after birth (all P<0.05) . The lung weight/body weight in the neonatal rats in LPS group were higher than those in NS and LPS+CM groups on day7 (both P<0.05) , but was higher compared only with NS group on day 14 ( P<0.05) , and lower compared only with LPS+CM group on day 21 ( P<0.05) ; the lung weight/body weight of neonatal rats in the three groups declined serially with days after birth (all P<0.05) . As shown by HE staining of lung tissue, the neonatal rats in NS group presented intact lung tissue architecture with evenly dilated alveoli, no intraseptal thickening albeit minimal inflammatory infiltration, and clear intra-alveolar space; the neonatal rats in LPS group presented fewer number of alveoli, large ralveolarsize, less alveolar septum, occasionally thickened alveolar septa, and inflammatory infiltration of the septum; the neonatal rats in the LPS+CM group presented better profiles in alveolar number and size, alveolar septum and intraseptal inflammatory infiltration compared with the LPS group, suggesting milder severity of lung injury. On day 7, the neonatal rats in the LPS group showed lower lung tissue RAC compared only with the NS group ( P<0.05) ; and so were on days 14 and 21, compared with NS group and LPS+CM group (both P<0.05) . The lung tissue RAC in the three groups of neonatal rats increased serially with days after birth (all P<0.05) . Compared with the NS group, the serum IL-6 level were higher in LPS group on days 7, 14, and 21 (all P<0.05) , and in LPS+CM group on days 7 and 21 (both P<0.05) . The serum IL-6 level were higher in LPS+CM group than those in LPS group on days 14 and 21 (both P<0.05) . The serum IL-6 in three groups decreased with days after birth (all P<0.05) . Compared with NS and LPS+CM groups, the serum IL-10 level in the LPS group was lower on day 7 (both P< 0.05) . The serum IL-10 level in three groups decreased with days after birth (all P<0.05) . The serum TNF-α level were higher in the LPS group than those in the NS group on days 7, 14, and 21 (all P<0.05) , and was higher than that in the LPS+CM group on day 14 ( P<0.05) . The serum TNF-α level increased with days after birth (all P<0.05) . Conclusion:Intraperitoneal injection of LPS in rats at 20 and 21 days of pregnancy can successfully established a lung injury model caused by intrauterine infectionin neonatal rats. In turn, the intrauterine infection leads to inflammatory cytokines changes, higher expression of pro-inflammatory factors and lower expression of anti-inflammatory factors in the neonatal rats. CM intervention exhibits certain protective effects against lung injury caused by intrauterine infectionin neonatal rats.