目的探讨上皮钙黏蛋白E-Cadherin及染色质重塑复合物Brg1在脂多糖(LPS)诱导的急性肺损伤(acute lung injury,ALI)小鼠模型中的表达与意义。方法将6~8周龄雌性Balb/c小鼠分为对照和LPS组,分别经气管插管给予等体积的生理盐水或LPS(5 mg/kg),每组8只,3 d后肺功能测定AHR,收取肺组织、HE染色观察肺部病理损伤,计数肺泡灌洗液(BALF)中细胞总数及分类,Western blot及免疫组化检测E-Cadherin及Brg1蛋白表达,ELISA检测TNF-α、单核趋化因子MCP-1的质量浓度。结果 LPS组肺组织炎症及评分较对照组明显增高。LPS组BALF中细胞总数较对照组增加,且以中性粒细胞为主。LPS组肺组织中E-Cadherin表达较对照组降低,而Brg1表达较对照组明显增高。LPS组BALF中TNF-α、MCP-1的质量浓度都较对照组增高。结论 LPS诱导的ALI模型中上皮钙黏蛋白E-Cadherin蛋白表达降低及染色质重塑复合物Brg1增高,对于研究急性肺损伤疾病的分子机制具有重要的临床指导意义,为疾病早期靶向分子筛查提供了科学依据。
To investigate the expression and significance of E-Cadherin and Brg1 in mice induced by lipopolysaccharide(LPS), female Balb/c mice(6-8 weeks old) were divided into control group and LPS group with 8mice in each group, and respectively administrated with PBS and LPS(5 mg/kg) by tracheal intubation. Three days after treatment, airway hyper-response(AHR) of the mice was assessed, and the mice were sacrificed by cervical dislocation to collect lung tissues. The infiltration of inflammatory cells in bronchoalveolar lavage fluid(BALF) were calculated; the expressions of E-Cadherin and Brg1 in the lung tissue were measured by Western blotting and immunohistochemistry; while the concentration of TNF-α and MCP-1 in BALF were detected by ELISA. Data showed that the count of neutrophils was remarkably higher in the LPS group than that of control group. Lung tissues damage was significantly increased in LPS group compared to control group; AHR of the LPS group was higher than that of control. The expression level of E-Cadherin in the LPS group was decreased while level of Brg1 was markedly higher in the LPS group compared with the control group. TNF-α and MCP-1 in BALF of LPS group were markedly higher than those of control. In conclusion, E-Cadherin expression is decreased and the chromatinremodeling complex Brg1 is increased in ALI model induced by LPS, which has important clinical significance for the molecular mechanism of acute lung injury, as the target of early diseases to provide scientific basis for molecular screening.