氧化磷脂对内毒素信号通路的影响及对急性胰腺炎的治疗作用  

The effect of OXPAPC in LPS signal pathway and acute pancreatitis

作　　者：李磊[1] 王兴鹏[1] 吴恺[1] 

机构地区：[1]上海交通大学附属第一人民医院消化科

出　　处：《中华急诊医学杂志》2006年第2期113-116,共4页Chinese Journal of Emergency Medicine

基　　金：上海市科技启明星资助项目(99Q814009)

摘　　要：目的探讨氧化磷脂(OXPAPC)对内毒素信号通路的影响及其对急性坏死型胰腺炎(ANP)的治疗作用。方法88只SD大鼠随机分为ANP模型组和OXPAPC治疗组。ANP模型制备采用胰管内逆行注射5%牛磺胆酸钠,OXPAPC治疗组在造模后0h、6h给予OXPAPC(25mg/kg)腹腔注射,并观察死亡率;其余于造模后12h、24h、48h及72h分批处死,检测血清淀粉酶和乳酸脱氢酶(LDH)活性;酶组织化学检测胰腺组织中性粒细胞髓过氧化物酶(MPO)活性改变;RTPCR检测胰腺组织炎性介质mRNA表达;western印迹检测细胞内信号转导蛋白激酶表达的变化;EMSA检测核因子蛋白活性。结果OXPAPC治疗组大鼠死亡率显著低于ANP组;OXPAPC治疗组血清淀粉酶活性及LDH活性于第12小时和第24小时显著降低;OXPAPC治疗组胰腺组织坏死和炎性细胞浸润程度显著减轻;OXPAPC治疗组胰腺组织MPO活性显著降低,炎性介质mRNA表达呈不同程度的下调,细胞内信号转导蛋白激酶表达下调,转录因子活性减弱。结论OXPAPC可阻断内毒素信号通路,从而显著降低实验性ANP的严重程度。Objective To investigate the effects of oxidized 1-palmitoyl-2- arachidonoyl-sn- glycere-3-phosphorylcholine （OXPAPC） in LPS signal pathway and acute neerotizing pancreatitis （ANP）. Methods Eighty-eight SD rats were randomly divided into two groups： ANP group and ANP treat with OXPAPC group. ANP model was induced by injecting sodium tauroeholate （5 % ） into pancreatic duet OXPAPC group was administered with OXPAPC at 0 hours and 6 hours after model establishment. Twenty rats from each group were separated to observe mortality. The others were killed at 12 hours, 24 hours, 48 hours and 72 hours respectively to detect serum levels of amylase and lactate dehydrogenase （LDH）. Severity of pancreatitis was evaluated by histological score system. The activity of myeloperoxidase （MPO） in pancreas was determined by zymohistochemistry. Inflammatory factors mRNA hours after treated with OXPAPC were studied by semi-quantitative RT-PCP. Intracellular proteinase were investigated by western blot. EMSA was used to testify the activity of transcriptional factors. Results The mortality in OXPAPC group was significantly than that in ANP group. Serum amylase and LDH levels at significantly decreased the 12 hours and 24 hours after treated with OXPAPC. Histologically, OXPAPC reduced the severity of pancreatic injury including inflammatory cell infiltration and necrosis at 12 hours, 24 hours, and 48 hours. There was a significant decrease of MPO activity in OXPAPG group compared to ANP group. Levels of inflammatory factors mRNA were reduced in OXPAPC group. Intracellular proteinase were down-regulated in OXPAPC group. EMSA showed that the activity of transcriptional factors weakened. Conclusion OXPAPC can block LPS signal pathway, so it can decrease the severity of ANP.

关 键 词：急性坏死型胰腺炎 磷脂类 内毒素 治疗效果 

分 类 号：R576[医药卫生—消化系统] R542.2[医药卫生—内科学]