中文摘要：

目的 探讨氯沙坦对急性肺损伤（ALI）肺炎症损伤程度和肺树突状细胞（DC）功能状态的影响及保护性效应及机制.方法 C57BL/6小鼠数字法随机分为：（1）对照组：气管内注射与脂多糖（LPS）等体积的磷酸盐缓冲液（PBS）,气管内注射PBS前30 min,予以腹腔内注射等体积PBS;（2） ALI组（ALI）：气管内注射LPS 2 mg/kg复制ALI模型,气管内注射LPS前30 min,予以腹腔内注射等体积PBS; （3） ALI＋氯沙坦组（Los）：气管内注射LPS 2 mg/kg前30 min,予以腹腔内注射氯沙坦15 mg/kg.注射LPS或PBS后6、24、48 h处死小鼠,留取肺组织待检.光镜观察肺组织病理改变,计算肺损伤评分,并测定肺湿重/体重比（LW/BW）.酶联免疫吸附法测定肺组织匀浆中白细胞介素（IL）-6浓度.流式细胞术（FCM）测定肺单细胞悬液中DC比例及CD80、MHCⅡ表达水平.结果 ALI组小鼠肺LW/BW明显高于对照组相应时间点肺LW/BW[（0.62 ±0.06）比（0.49±0.03）],P＜0.05.氯沙坦干预组LW/BW（0.55±0.03）较ALI组明显下降,但仍显著高于对照组水平（P＜0.05）.ALI组肺组织病理检查见肺泡间隔增宽、肺泡间质内血管充血、出血及大量炎细胞渗出,应用氯沙坦使ALI小鼠肺组织病理损伤明显减轻,肺损伤评分显著降低[（3.09±0.45）比（5.10±0.24）],P ＜0.05.ALI组肺IL-6明显高于对照组,应用氯沙坦组可使ALI小鼠肺组织IL-6水平明显下降,但仍明显高于对照组[（1 983 ±219）比（335±168）],P＜0.05.流式细胞术检测显示ALI组肺DC比例显著升高,表达CD80的肺DC明显增加,氯沙坦组小鼠表达CD80的肺DC较ALI组明显下降,但仍显著高于对照组水平;ALI组和氯沙坦组表达MHCⅡ的DC差异无统计学意义（P＞0.05）.结论 氯沙坦对ALI具部分保护性效应,氯沙坦可能通过抑制肺DC成熟而对ALI具抗炎和免疫调节反应.

英文摘要：

Objective To assess the effects of losartan on the frequency and phenotype of respiratory dendritic cells （DC） in lipopolysaccharide （LPS）-induced acute lung injury （ALI） mice.Methods The C57BL/6 mice were randomly divided into 3 groups of control,ALI and ALI＋ losartan.ALI animals received 2 mg/kg of LPS; ALI＋ losartan animals 2 mg/kg of LPS and 15 mg/kg of losartan 30 min before an intratracheal injection of LPS; control animals phosphate buffer saline （PBS） instead of LPS.Lung wet weight/body weight （LW/BW） was recorded to assess lung injury.The pathological changes were examined under optical microscope.The frequency and phenotype of pulmonary DC were characterized by flow cytometry.Meanwhile,the levels of IL-6 in lung homogenates were assessed by enzyme-linked immunosorbent assay （ELISA）.Results （1） The LPS-induced rise in LW/BW was partially prevented by a pretreatment of losartan.（2） Histologically,widespread alveolar wall thickening caused by edema,severe hemorrhage in interstitium and alveolus and marked and diffuse interstitial infiltration of inflammatory cells were observed in the ALI group.Whereas,losartan effectively attenuated the LPS-induced pulmonary hemorrhage,leukocytic infiltration in interstitium and alveolus.（3） Meanwhile,the levels of IL-6 in lung tissue were significantly enhanced in the LPS-induced ALI mice.Yet after a pretreatment of losartan,the pulmonary level of IL-6 markedly decreased.（4） LPS dosing resulted in a rapid accumulation of DC in lung tissues and an up-regulated expression of CD80 in LPS-induced ALI.In contrast,the expression of MHC Ⅱ on respiratory DC was not significantly different among groups.A pretreatment of losartan led to a marked reduction in CD80 expression on pulmonary DC （P 〈 0.05 vs ALI）.Conclusion Losartan may downregulate pulmonary injury by inhibiting the activation of pulmonary DC.