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目的探讨p38信号通路在丙泊酚抑制呼吸机所致肺损伤(VILI)大鼠肺组织表达高迁移率族蛋白B1(HMGB1)中的作用。方法将32只健康SD大鼠随机分为4组,每组8只。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30ml/kg;大潮气量通气+丙泊酚组(D组)VT为30ml/kg,同时静脉注射丙泊酚8mg/(kg.h)。机械通气4h后处死动物,测定支气管肺泡灌洗液(BALF)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蛋白含量以及p38的激酶活性,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4h后,与A组相比,C组总蛋白水平(1.58±0.46)g/L、白细胞计数(112.05±21.33)×107/L、肺W/D比值(8.25±0.92)、MPO活性(3.08±0.85)U/g、HMGB1蛋白(0.43±0.13)和mRNA(0.30±0.08)表达以及p38激酶活性(0.52±0.11)均明显增加(P<0.05);与C组相比,D组上述各项指标的变化均明显降低(P<0.05)。结论丙泊酚可改善VILI肺内炎症反应,可能与通过p38信号通路抑制HMGB1蛋白和mRNA的表达有关。
OBJECTIVE: To investigate the role of p38 signaling pathway in propofol-induced lung injury induced by ventilator-induced lung injury (VILI) in high mobility group box 1 protein (HMGB1). Methods Thirty-two healthy SD rats were randomly divided into 4 groups with 8 rats in each group. In control group (group A), mechanical ventilation was not performed and spontaneous respiration was maintained; tidal volume (VT) in routine ventilation group (group B) was 8ml / kg; VT in large tidal volume ventilation group (group C) was 30ml / kg; The pooled group (group D) VT was 30ml / kg, while intravenous propofol 8mg / (kg.h). After 4 hours of mechanical ventilation, the animals were sacrificed and the total protein level, white blood cell count, lung wet / dry weight ratio (W / D) and neutrophil myeloperoxidase (MPO) activity in bronchoalveolar lavage fluid (BALF) were measured. Western blot was used to detect HMGB1 protein content and p38 kinase activity in lung tissue. The expression of HMGB1 mRNA was detected by RT-PCR. One-way ANOVA was used to compare the different groups. Results Compared with group A, total protein level (1.58 ± 0.46) g / L, white blood cell count (112.05 ± 21.33) × 107 / L, lung W / D ratio (8.25 ± 0.92), MPO activity (3.08 ± 0.85) U / g, HMGB1 protein (0.43 ± 0.13) and mRNA (0.30 ± 0.08) and p38 kinase activity (0.52 ± 0.11) Changes in these indicators were significantly lower (P <0.05). Conclusion Propofol can improve pulmonary inflammatory response in VILI, which may be related to the inhibition of HMGB1 protein and mRNA expression through p38 signaling pathway.