摘要目的:评价博舒替尼对内毒素血症小鼠急性肺损伤的影响。方法:清洁级健康雄性C57BL/6小鼠60只，8~12周龄，体重20~25 g，采用随机数字表法分为4组( n＝15)：对照组(C组)、博舒替尼组(B组)、内毒素血症组(LPS组)和博舒替尼+内毒素血症组(B+LPS组)。采用腹腔注射LPS 10 mg/kg的方法制备内毒素性急性肺损伤模型。B+LPS组于造模前0.5 h、B组于相应时点，尾静脉注射博舒替尼5 mg/kg。于造模后24 h时，处死小鼠，观察肺组织病理学结果，并行肺损伤评分，计算肺系数(LI)、肺湿重/干重(W/D)比值；行伊文思蓝染色，检测肺组织伊文思蓝含量；采用Western blot法检测血管内皮钙黏蛋白(VE-cadherin)、血管细胞粘附分子1(VCAM-1)、血管内皮钙黏蛋白(VE-cadherin)、磷酸化核转录因子κB p65(p-NF-κB p65)和磷酸化核因子κB抑制蛋白α(pIκB-α)的表达，采用RT-PCR法检测IL-1β、IL-6、TNF-α的mRNA表达。 结果:与C组比较，LPS组LI、肺W/D比值、肺组织伊文思蓝含量和肺损伤评分升高，肺组织IL-1β mRNA、TNF-α mRNA、IL-6 mRNA、VCAM-1、p-NF-κB p65和pIKB-α表达上调，VE-cadherin表达下调( P<0.05)，B组上述指标比较差异无统计学意义( P>0.05)。与LPS组比较，B+LPS组LI、肺W/D比值、肺组织伊文思蓝含量和肺损伤评分降低，肺组织IL-1β mRNA、TNF-α mRNA、IL-6 mRNA、VCAM-1、p-NF-κB p65和pIKB-α表达下调，VE-cadherin表达上调( P<0.05)。 结论:博舒替尼可减轻内毒素血症小鼠急性肺损伤。

abstractsObjective:To evaluate the effects of bosutinib on acute lung injury in mice with endotoxemia.Methods:Sixty clean-grade healthy male C57BL/6 mice, aged 8-12 weeks, weighing 20-25 g, were divided into 4 groups ( n=15 each) using a random number table method: control group (group C), bosutinib group (group B), endotoxemia group (group lipopolysaccharide [LPS]) and bosutinib plus endotoxemia group (group B+ LPS). Septic acute lung injury model was developed by intraperitoneal injection of LPS.Bosutinib 5 mg/kg was injected via the tail vein at 0.5 h before establishing the model in group B+ LPS and at the corresponding time point in group B. At 24 h after developing the model, the mice were sacrificed for microscopic examination of the pathological results of lung tissues which were scored for calculation of the lung coefficient (LI) and wet/dry lung weight (W/D) ratio, and for determination of the content of Evans blue in lung tissues (by Evans blue staining), expression of vascular endothelial cadherin (VE-cadherin), vascular cell adhesion molecule 1 (VCAM-1), phosphorylated nuclear transcription factor κB p65 (p-NF-κB p65), phosphorylated nuclear factor κB inhibitory protein α (pIκB-α) (by Western blot) and expression of interleukin-1beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α) mRNA (using real-time polymerase chain reaction). Results:Compared with group C, the LI, W/D ratio, Evans blue content in lung tissues and lung injury score were significantly increased, and the expression of IL-1β mRNA, TNF-α mRNA, IL-6 mRNA, VCAM-1, p-NF-κB p65 and pIKB-α was up-regulated, and the expression of VE-cadherin was down-regulated in group LPS ( P<0.05), and no significant change was found in the parameters mentioned above in group B ( P>0.05). Compared with group B, the LI, W/D ratio, Evans blue content in lung tissues and lung injury score were significantly decreased, and the expression of IL-1β mRNA, TNF-α mRNA, IL-6 mRNA, VCAM-1, p-NF-κB p65 and pIKB-α was down-regulated, and the expression of VE-cadherin was up-regulated in group LPS ( P<0.05). Conclusions:Bosutinib can ameliorate the acute lung injury in mice with endotoxemia.