异氟醚预处理对缺血/再灌注复合内毒素大鼠肝脏损伤的影响

目的 观察再灌注期腹腔注射内毒素脂多糖(LPS)对大鼠肝脏缺血/再灌注(I/R)损伤的影响以及异氟醚(ISO)预处理的干预作用.方法 将32只SD大鼠随机均分为4组:假手术(Sham)组、单纯肝脏I/R组、肝脏I/R复合LPS损伤(I/R+LPS)组及ISO预处理组.I/R+LPS组吸氧预处理后间隔0.5 h进行肝脏缺血1 h、再灌注4 h,再灌注开始时腹腔内注入LPS;ISO预处理组以ISO吸入预处理0.5 h,间隔0.5 h后进行I/R损伤操作,再灌注开始时腹腔内注入LPS.再灌注4 h处死各组动物,留取肝脏及血液标本;观察各组肝组织病理学改变,血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、肿瘤坏死因子-α(TNF-α)的变化以及肝组织TNF-α、髓过氧化物酶(MPO)活性的改变.结果 与Sham组比较,损伤各组血清ALT、AST、TNF-α及肝组织TNF-α、MPO活性均显著升高(P均＜0.01);与I/R组比较,I/R+LPS组肝脏损伤和炎症细胞因子反应明显较重(P＜0.05或P＜0.01)l与I/R+LPS组比较,ISO预处理组肝脏的病理损伤明显较轻,血清ALT、AST、TNF-α水平及肝组织MPO活性和促炎细胞因子TNF-α的表达水平均显著降低(P均＜0.05).结论 再灌注期复合LPS腹腔注射明显加重了肝脏的损伤和炎症细胞因子反应,ISO预处理可明显减轻复合损伤介导的炎症反应,保护肝脏.

Isoflurane pretreatment reduced liver injury induced by ischemia/reperfusion combined with lipopolysaccharide in rats

OBJECTIVE: To investigate the effect of lipopolysaccharide (LPS) on ischemia/reperfusion (I/R) injury of liver and the protective effect of isoflurane (ISO) pretreatment on such injury in rat. METHODS: Thirty-two male Spregue-Dawley(SD) rats were randomly assigned to 4 groups: Sham group, only receive anesthesia and laparotomy; I/R group; I/R+LPS group, with 1 hour of hepatic ischemia and 4 hours of reperfusion, and LPS was given at the beginning of reperfusion; ISO group, received ISO pretreatment for 0.5 hour, then 1 hour of hepatic ischemia followed by 4 hours of reperfusion and LPS given at the beginning of reperfusion. The pathological changes in the liver tissue were assessed. Alanine aminotransferase (ALT), aspartate aminotrasferase (AST), the myeloperoxidase (MPO) activity in liver tissue, hepatic and serum tumor necrosis factor-alpha (TNF-alpha) were determined. RESULTS: Compared with Sham group, ALT, AST, TNF-alpha in serum and MPO activity in liver tissue, hepatic and serum TNF-alpha were increased significantly in all injury groups (all P<0.01). Compared with ISO group alone, hepatic I/R combined with LPS resulted in severer liver injury, with the levels of ALT, AST in serum, MPO activity in the liver tissue, and hepatic and serum TNF-alpha level were all increased (all P<0.05). Compared with I/R+LPS group, both the liver injury and inflammatory reaction were significantly reduced in I/R group (P<0.05 or P<0.01). CONCLUSION: LPS injection during reperfusion results in severer liver injury and inflammatory reaction after hepatic I/R in rats. ISO pretreatment for 30 minutes might reduce the inflammatory reaction and live injury induced by hepatic I/R combined with LPS.