p38信号通路参与呼吸机所致肺损伤大鼠高迁移率族蛋白B1的表达

目的 研究p38信号通路在呼吸机所致肺损伤(ventilator-induced lung injury,VILI)大鼠肺组织表达高迁移率族蛋白BI(high mobility group box 1 protein,HMGB1)中的作用.方法健康sD大鼠24只随机分为3组:对照组(A组)不行机械通气,保留自主呼吸;常规通气组(B组)潮气量(Vt)为8mL/kg;大潮气量通气组(C组)Vt为40 mL/kg.机械通气4 h后处死动物,测定支气管肺泡灌洗液中总蛋白水平、白细胞计数以及肺湿干重比值(W/D)和中性粒细胞髓过氧化物酶(MPO)活性.采用Western blot方法检测肺组织HMGB1蛋白和p38激酶活性变化,采用RT-PCR方法检测HMGB1 mRNA的表达.应用单因素方差分析进行不同组别间的比较.结果 通气4 h后,与A组相比,C组总蛋白水平(1.77±0.68)g/L、白细胞计数(106.55±28.17)×10~7 L~(-1)、肺W/D比值(7.16±1.02)、MPO活性(3.94±1.21)U/g、HMGB1蛋白(0.64±0.17)和mRNA(1.17±0.45)表达以及p38激酶活性(0.51±0.12)均明显增加(P<0.05),而B组上述各项指标的变化均无统计学意义(P>0.05).结论大潮气量机械通气可引起大鼠急性肺损伤,p38参与了机械牵张诱导肺组织HMGB1的表达.

p38 signaling pathway involved in the expression of HMGB1 in a rat model of ventilator-indnced lung injury

Objective To investigate the role of p38 MAPK pathway in the expression of high mobility group box 1 (HMGB1) in lung tissue in a rat model of ventilator-induced lung injury. Method Twenty-fonr healthy Sprague Dawley (SD) rats were randomly divided into 3 groups (n = 8 each) : group A, spontaneous breathing; group B, small tidal volume ventilation (Vt = 8 mL/kg) and group C, high tidal volume ventilation (Vt = 40 mL/kg). 1he animals in group B and C were mechanically ventilated for 4 hours and all animals were sacri-riced. The lungs were removed for: (1) lung lavage and determination of total protein contnt and WBC and neu-trophil counts in broncho-alveolar lavage fluid (BALF) ; (2) determination of W/D lung weight ratio and myelop-erexidnse (MPO) activity; (3) detennination of HMGB1 protein and mRNA expression and p38 MAPK activity in lung tissue. Differences within the groups were analyzed using One way ANOVA. Results The inflammatory re-sponse as evidenced by total protein (1.77 ± 0.68) g/L and WBC (106.55 ± 28.17) × 10~7/L in BALF, W/D lung weight ratio (7.16±1.02) and MPO activity (3.94±1.21) U/g were significantly higher in group C com-pared with group A (P <0.05); HMGB1 protein (0.64±0.17) and mRNA (1.17±0.45) expression and p38 activity (0.51±0.12) also significantly increased in group C (P <0.05). Of the above indexes, there were no statistical differences between group B and group A (P > 0.05). Conclusions High tidal volume ventilation in-daces acute lung injury, which may be related with upregulation of HMGB1 expression through p38 MAPK signal pathway.