丙戊酸钠对烧伤休克大鼠肺微血管内皮细胞活化和通透性的影响

目的观察组蛋白去乙酰化酶抑制剂丙戊酸钠（VPA）对大鼠50%TBSAⅢ度烧伤休克模型肺微血管内皮细胞（PMEC）活化和通透性的影响。方法雄性SD大鼠随机分为4组：假烫组,烫伤组（给予50%TBSAⅢ度烫伤）,烫伤＋VPA组及烫伤＋2M2P组（烫伤后即刻皮下注射VPA 300 mg/kg或对照药物2-甲基-2-戊烯酸,即2M2P300 mg/kg）。分别于烫伤后2 h、6 h及12 h,伊文斯蓝（EB）染色法检测肺血管通透性;采血检测红细胞压积（HCT）及脏器功能指标;HE染色观察肺组织病理变化,干湿重法检测肺组织含水率;免疫组化法检测肺组织血管内皮细胞生长因子（VEGF）、E-选择素（E-selectin）和细胞间黏附分子-1（ICAM-1）的表达;TUNEL法检测肺微血管内皮细胞（PMEC）凋亡率。结果与烫伤组比较,伤后2 h及6 h烫伤＋VPA组和烫伤＋2M2P组血HCT和肺组织含水率降低,肺血管通透性明显降低（P〈0.05）,肺水肿等病理改变减轻;烫伤＋VPA组PMEC凋亡率低于烫伤＋2M2P组（P〈0.05）。烫伤＋VPA组VEGF、E-selectin、ICAM-1阳性率均显著低于烫伤组和烫伤＋2M2P组（P〈0.05）。结论 VPA能抑制烧伤休克大鼠肺血管内皮细胞的活化以及凋亡,从而减少血管通透性增加引起的血容量丢失。

Effect of Sodium Valproate on Activation and Permeability of Pulmonary Microvascular Endothelium Cells in Rats with Burn Shock

Objective To observe the effect of Sodium Valproate（ VPA） on activation and permeability of pulmonary microvascular endothelium cells（ PMEC） in burn shock rats with third degree burn and 50% TBSA. Methods Male SD rats were randomly divided into sham group（ group A）,ambustion group suffered 50% TBSA ambustion（ group B）,ambustion and VPA group（ group C） and ambustion and 2-methyl-2-pentenoic acid group（ 2M2P,group D）,and the group D was subcutaneously injected with 300 mg /kg VPA or 300 mg /kg 2M2P after injury. Pulmonary vascular permeabilities were detected with evans blue（ EB） staining method at 2,6 and 12 h postinjury; haematocrit（ HCT） and organ function indexes were detected by blood collection; pathological changes and water content of lung tissues were observed with hematoxylin and eosin（ HE） stain method and detected with oven drying method respectively; meanwhile expressions of vascular endothelial cell growth factor（ VEGF）,E-selectin and ICAM-1 contents were detected with immunohistochemical method; apoptosis rates of pulmonary microvascular endothelial cell（ PMECs） were detected with TUNEL method. Results Compared with group B,blood HCT levels,water contents and permeability of pulmonary tissues at 2 h and 6 h postinjury were significantly lower in group C and D（ P ＆lt; 0. 05）,and pathological changes in the two groups were also alleviated; while the apoptosis rate of PMECs in group C was significantly lower than that in group D（ P ＆lt;0. 05）. Expressions of VEGF,E-selectin and ICAM-1 positive rates in group C were significantly lower than those in group B and D（ P ＆lt; 0. 05）. Conclusion VPA can inhibit activation and apoptosis of PMECs in rats with burn shocks,which may decrease blood volume losses induced by the increase of vascular permeability.