羟乙基淀粉130/0．4对脓毒症大鼠肺毛细血管通透性、炎性细胞因子及NF-κB表达的影响

Effect of hydroxyethyl starch （HES 130/0.4 ） on pulmonary capillary permeabmty, expression of inflammatory cytokines and nuclear factor kappa B in a rat model of sepsis

目的 研究羟乙基淀粉130/0．4（HES 130/0．4）对脓毒症大鼠肺毛细血管通透性、炎性细胞因子、中性粒细胞浸润及NF-κB表达的影响。方法 36只雄性SD大鼠,随机分为6组,每组6只,假手术组（Sham组）和HES 130/0．4对照组（HES组）大鼠只开腹、牵引盲肠、复位、关腹和复苏,但盲肠不结扎也不穿孔;脓毒症组（S组）采用盲肠结扎穿孔（CLP）的方法建立脓毒症大鼠模型;脓毒症＋ HES1-3组（S＋H1-3组）分别于CLP后4h时静脉输注HES 7．5、15、30ml/kg,Sham组和S组均于相应时点静脉输注生理盐水30 ml/kg,HES组静脉输注HES 130/0．4 30 ml/kg,输注速率为0．2 ml/min。于CLP后6h内持续监测心率和平均动脉压,CLP后6h处死大鼠,取肺组织,计算含水量,测定毛细血管通透性、炎性细胞因子（TNF-α、IL-6、IL-10）及细胞核内NF-κB的表达,光镜下观察肺组织病理学。Sham组、HES组、S组、S＋H1组、S＋H2组及S＋H3组各另取16只大鼠,于CLP后连续4d观察大鼠生存情况。结果 与Sham组比较,S＋H1组、S＋H2组、S＋H3组肺毛细血管通透性、含水量、TNF-α、IL-6、IL-10水平、NF-κB表达均升高（P＜0．05）;与S组比较,S＋H1组TNF-α的水平、S＋H2组、S＋H3组毛细血管通透性、含水量、TNF-α、IL-6水平降低,S＋H2组IL-10水平升高,S＋H1组、S＋H2组、S＋H3组NF-κB表达降低（P＜0．05）,S＋H2组肺组织中性粒细胞浸润程度减轻;S＋H1组、S＋H2组、S＋H3组4d内大鼠生存率差异无统计学意义（P＞0．05）。结论 HES 130/0．4 15 ml/kg可改善脓毒症大鼠肺毛细血管通透性,下调促炎细胞因子（TNF-α、IL-6）、上调抗炎细胞因子（IL-10）的表达,抑制中性粒细胞的浸润及NF-κB表达。

Objective To investigate the effect of hydroxyethyl starch （HES 130/0.4 ） on pulmonary capillary permeability, expression of inflammatory cytokines and nuclear factor kappa B （NF-κB）, neutrophil infiltration and activation in a rat model of sepsis. Methods Thirty-six male SD rats weighing 280-320 g were randomly divided into 6 groups （ n = 6 each） ; group Ⅰ sham operation：abdomen was opened and closed; group Ⅱ sepsis was induced by cecal ligation and puncture （CLP） ; group Ⅲ , Ⅳ and Ⅴ CLP ＋ HES 7.5, 15 and 30 ml/ kg, and group Ⅵ received HES 30 ml/kg without sepsis. The animals were anesthetized with intraperitoneal pentobarbital. The vein in the tail was cannulated for continuous infusion. Left carotid artery was cannulated for MAP and HR monitoring. The animals were killed at 6 h after CLP for determication of pulmonary capillary permeability （2% Evan＇s blue via jugular vein at 15 min before the animal being killed）, water content in the lung, inflammatory cytokines （TNF-α, IL-6 and IL-10） levels, NF-κB activity and neutrophil infiltration in the lung. Results Infusion of different volumes of HES 130/0.4 during the 6 h after CLP did not affect MAP and HR. HES 130/0.4 15 ml/kg significantly decreased pulmonary permeability, water and IL-6, TNF-α content, NF-κB activity and neutrophil infiltration and increased IL-10 content in the lung in group Ⅳ as compared with group Ⅱ（CLP）. There was no significant difference in the survival rate between group Ⅱ （CLP） and the 3 CLP ＋ HES groups （ Ⅲ, Ⅳ, Ⅴ ）. Conclusion HES 130/0.4 15 ml/kg can reduce pulmonary capillary leakage, IL-6 and TNF-α content, NF-κB activity and neutrophil infiltration in the lung in a rat model of sepsis.