目的观察内毒素肺损伤发病中小鼠肺组织及肺泡巨噬细胞(AM)清道夫受体A(SR-A)表达的变化。方法腹腔注射内毒素脂多糖(LPS)复制小鼠急性肺损伤模型,实验分为LPS致伤后0.5、1、2、4和8h组及对照组,用小鼠AM株J774A.1细胞作体外实验,分为LPS作用后0.5、1、2、4和8h组及无血清培养液对照组。用免疫组化及流式细胞仪观察分析小鼠肺组织及AM、J774A.1细胞的SR-A表达及分布。结果LPS各组小鼠动脉血氧分压(PaO2)均明显低于对照组,且肺湿/干重(W/D)比值明显高于对照组(P均〈0.01)。对照组小鼠肺组织除支气管上皮细胞、淋巴细胞无SR-A表达外,AM、肺血管内皮细胞、血管平滑肌细胞、肺泡上皮细胞、中性粒细胞胞膜及胞质均有SR-A表达。LPS致伤后0.5h即可观察到肺组织SR-A免疫组化染色弱于对照组,并且随着致伤时间延长.染色逐渐变浅,表明内毒素肺损伤发病中肺内SR-A表达减少。用J774A.1细胞作体外实验也发现类似结果,以4h和8h组降低最为显著。流式细胞仪检测AM及J774A.1细胞的SR-A表达与免疫组化染色结果相符,且细胞膜SR-A下降较细胞总SR-A显著。结论内毒素肺损伤小鼠肺组织及AM的SR-A表达减少,其表达变化可能与内毒素作用有关。
Objective To investigate the expression of scavenger receptor class A (SR-A) in lung tissue and alveolar macrophage (AM) in mice with acute lung injury (ALI) induced by lipopolysaccharide (LPS). Methods The model of ALI was reproduced by intraperitoneal (ip) injection of LPS (5 mg/kg), and the expression of SR-A was observed in lung tissue and AM, and the expression and distribution of J774 A. 1 were also studied by using mouse macrophage line. Results Partial pressure of oxygen in artery (PaO2) of lung tissue in LPS groups was significantly lower while wet/dry weight (W/D) ratio was higher than those in normal saline control group (both P〈0. 01). SR-A was widely expressed in routine lung, including AM, pulmonary vascular endothelial cells, vascular smooth muscle cells, lung epithelial cells and polymorphonuclear neutrophils. Immunohistochemical staining showed that, during the course of development of ALI in mice, the expression of SR-A was gradually down-regulated with the elapse of time after ip injection of LPS, The same result was seen in the isolated AM, and especially marked in group 4 hours and group 8 hours. In vitro, the expression of SR-A on J774 A. 1 cells decreased was also down-regulated when treated with LPS. Conclusion SR-A was widely expressed in murine lung. During the course of ALI, the expression of SR-A in the routine lung and AM is down-regulated, which may be induced by LPS.