首页> 中文期刊>中华危重病急救医学 >多烯磷脂酰胆碱对脓毒症大鼠肝脏的保护作用

多烯磷脂酰胆碱对脓毒症大鼠肝脏的保护作用

摘要

目的 观察多烯磷脂酰胆碱(PPC)对脓毒症大鼠肝脏的保护作用.方法 将50只健康雄性SD 大鼠按随机数字表法分为正常对照组(10只)、模型组(15只)、PPC对照组(10只)和PPC保护组(15只).通过腹腔注射单剂大肠杆菌脂多糖(LPS)6 mg/kg建立脓毒症大鼠模型;正常对照组和PPC对照组给予等量生理盐水.PPC对照组和PPC保护组在注射LPS前24 h和6 h分别通过大鼠尾静脉给予等倍稀释的PPC 10 ml/kg(232.5 mg/kg);正常对照组和模型组给予等量的5%葡萄糖溶液.观察注射LPS后24 h内各组大鼠的行为改变和死亡率;处死动物后取静脉血检测丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST);留取肝脏测定大鼠全肝重/体重比值(L/Wb)和肝湿重/干重比值(W/D),并行组织病理学检查,用免疫组化二步法检测肝组织中细胞间黏附分子-1(ICAM-1)的表达.结果 正常对照组和PPC对照组大鼠精神状态正常;模型组大鼠精神萎靡,饮水、活动少;PPC保护组精神状态较好,饮水、活动较好.PPC保护组大鼠死亡率明显低于模型组[6.7%(1/15)比46.7 %(7/15),P<0.05].PPC保护组血浆ALT和AST水平、L/Wb比值、W/D 比值及肝组织ICAM-1阳性率均低于模型组[ALT(U/L):157.71±32.63比225.63±43.47;AST(U/L):53.21±13.85比85.25±18.91;L/Wb比值:(4.09±0.28)%比(4.50±0.25)%;W/D比值:3.52±0.27比3.84±0.18;ICAM-1阳性率:35.7%(5/14)比87.5%(7/8),P<0.05或P<0.01].正常对照组与PPC对照组上述指标未见统计学差异.模型组大鼠肝脏炎症反应强烈,炎性细胞聚集,肝实质细胞水肿渗出明显;正常对照组和PPC对照组肝脏形态正常;而PPC保护组介于两者之间.结论 大鼠预防性注射PPC能阻止内毒素引起的进行性炎症紊乱,减轻肝脏水肿和炎症反应,减少肝脏ICAM-1的表达,保护肝功能,并降低死亡率.%Objective To investigate the protective effect of polyenylphosphatidyl choline(PPC)on liver in rat with sepsis.Methods A total of 50 healthy male SD rats were randomly divided into four groups according to random number table:normal control group(NS group,n=10),sepsis model group(LPS group,n=15),PPC control group(PPC group,n=10)and PPC protection group(P+L group,n=15).Asingle dose of lipopolysaccharide(LPS)6 mg/kg was injected to the peritoneal cavity to reproduce the sepsis model,while in NS group and PPC group,same volume of normal saline was used.PPC 10 ml/kg (232.5 mg/kg)was injected 24 hours and 6 hours before LPS via the tail vein in PPC group and P+L group,while in NS group and LPS group 5%glucose solution in the same volume was given.Behavioral changes and mortality rate of rats were recorded,and all survived rats were sacrificed 24 hours after LPS injection.Venous blood was taken for alanine aminotransferase(ALT)and aspartate aminotransferase(AST)determination.Ratios of liver weight/body weight(L/Wb)and wet wieght/dry weight of liver(W/D)were calculated.Histopathology changes in liver tissue were observed with hematoxylin eosin(HE)stain,and intercellular adhesion molecule-1(ICAM-1)expression with instant two-step immunohistochemistry.Results Twenty-four hours after LPS injection(LPS group),the rats became lethargic,with less activity and drinking,while rats in P+L group,showed much better mental status,water intake and activity than LPS group.The mortality rate of P+L group was significantly lower than that of LPS group[6.7%(1/15)vs.46.7%(7/15),P<0.05].Compared with LPS group,rats in P+L group had lower levels of plasma ALT and AST,L/Wb,W/D,and liver ICAM-1 positive expression ratio[ALT(U/L):157.71±32.63 vs.225.63±43.47; AST(U/L): 53.21±13.85 vs.85.25±18.91;L/Wb:(4.09±0.28)%vs.(4.50±0.25)%,W/D:3.52±0.27 vs.3.84±0.18,ICAM-1 positive expression ratio:35.7%(5/14)vs.87.5(7/8),P<0.05 or P<0.01].All parameters were normal in NS group and PPC group,and no statistical significance was observed between them(all P>0.05).LPS-injection led to severe inflammatory reaction in hepatic tissue,including obvious edema of hepatic parenchymal cells,exudation and aggregation of inflammatory cells,while in P+L group,these morphological changes were milder than that in LPS group but more obvious than that of NS group.Conclusion Pre-treatment of rats with PPC alleviates progressive inflammatory disturbances of hepafic tissue caused by endotoxin injection,and it attenuates liver edema and ICAM-1 expression,protects liver function and decreases mortality rate in rats with sepsis.

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