MitoKATP通道在异氟醚对急性肺损伤保护作用中的影响

目的:探讨MitoK_(ATP)通道在异氟醚预处理对急性肺损伤(acute lung injury, ALI)保护作用中的影响。方法:将30头5～6周龄、9～14 kg雄性幼猪随机分成5组(n=6),分别为对照组、脂多糖组(LPS组)、异氟醚组(ISO组)、5-羟基癸酸盐(5-hydroxydecanoate,5-HD)组(HD组)和HD-ISO组,分别静脉输注生理盐水、静脉输注内毒素、吸入异氟醚预处理后静脉输注内毒素、静脉输注5-HD预处理后静脉输注内毒素、静脉输注5-HD和吸入异氟醚预处理后静脉输注内毒素。ALI形成后观察外周血白细胞(WBC)的动态变化、肺泡灌洗液(broncho-alveolar lavage fluid, BALF)中总磷脂(total phospholipid, TPL)含量、肺组织IL-8 mRNA和ICAM-1 mRNA表达。结果:与对照组相比,LPS组在ALI形成时、ALI 2 h、4 h时WBC均明显下降(P0.05),肺组织IL-8 mRNA、ICAM-1 mRNA表达明显增加,BALF中TPL显著下降(P0.05),H-E染色示大量炎性细胞浸润。与LPS组相比,ISO组在ALI 4 h时WBC显著增加,肺组织IL-8 mRNA、ICAM-1 mRNA表达明显下降,BALF中TPL显著增加(P0.05),H-E染色示炎性细胞浸润明显减少。与ISO组相比,HD-ISO组在ALI 2 h和4 h时WBC显著减少,肺组织IL-8 mRNA、ICAM-1 mRNA表达明显增加;BALF中TPL显著下降(P0.05),H-E染色示炎性细胞浸润明显增加。结论:异氟醚预处理可能通过MitoK_(ATP)通道来抑制ALI时炎症因子和细胞黏附分子的释放。

Effect of MitoKATP channel on protective effect of isoflurane on acute lung injury

Objective: To explore the effects of MitoK_ATP channel on the protective effect of isoflurane pretreatment on acute lung injury induced by endotoxin in piglets. Methods: Thirty young piglets of 5-6 weeks old, weighing 9-14 kg were anesthetized, intratracheally intubated, and underwent mechanical ventilation. The animals were divided into 5 groups (n=6 each group):control group, lipopolysaccharide (LPS) group, isoflurane (ISO) group, 5-hydroxydeconate (HD) group, and HD-ISO group. Control group was pretreated by normal saline, and LPS group was pretreated by endotoxin. ISO group was pretreated by alveolar concentrations (MAC) isoflurane, HD group was pretreated by 5-HD, HD-ISO group was pretreated by 5-HD, isoflurane, each group was pretreated and then injected endotoxin. After the establishment of acute lung injury model, the animals were killed and lungs were processed for measurement of peripheral white blood cell (WBC), the interleukin (IL) -8 and intercellular cell adhesion molecule (ICAM)-1 mRNA level, total phospholipid content in bronchoalveolar lavage fluid (BALF). Results: Compared with control group, WBC was decreased at ALI 0 h, 2 h, and 4 h in LPS group after ALI induction, IL-8 mRNA and ICAM-1 mRNA were increased, the total phospholipid content in BALF was decreased (P<0.05), hematoxylin-eosin (HE) staining showed that there was significant inflammatory cell infiltration in the lung tissue. Compared with LPS group, WBC was increased at 4 h in ISO group after ALI induction, IL-8 mRNA and ICAM-1 mRNA were decreased, the total phospholipid content in BALF was increased (P<0.05), HE staining showed less inflammatory cellular infiltration. Compared with ISO group, WBC was decreased 2 h and 4 h in HD-ISO group after ALI induction, IL-8 mRNA and ICAM-1 mRNA were increased, the total phospholipid content in BALF was decreased (P<0.05), H-E staining showed more inflammatory cell infiltration. Conclusions: Inhalation of isoflurane may inhibit the release of inflammatory factors and cell adhesion factors in piglets with acute lung injury through MitoK_ATP channel.