脂氧素受体激动剂BML-111对小鼠重症急性胰腺炎影响的实验研究

Protective effects of lipoxin receptor agonist BML-111 on cerulein-induced experimental severe acute pancreatitis in mice

目的探讨脂氧素受体激动剂BML-111对小鼠重症急性胰腺炎的影响及可能机制。方法128只健康雄性Babl／cdx鼠随机分为4组，即①生理盐水对照组（NS组），②BML-111对照组（BML组）；③重症急性胰腺炎组（SAP组）；④BML-111治疗组（SAP＋BML组），每组又分为3h．6h、12h及24h共4个亚组，每组8只小鼠；采用蛙皮素联合脂多糖腹腔注射法建立小鼠SAP模型。SAP＋BML组及BML组分别于第一次注射前1h经腹腔注射BML-111。分别于最后一次注射后3h．6h、12h、24h处死小鼠采集标本，采用对-硝基苯麦芽七糖苷法检测血清淀粉酶（AMY）水平；双抗体夹心ELISA法检测血清C反应蛋白（CRP）、IL-10、TNF—α、IL-1β含量；胰腺组织行苏木素～伊红染色（H-E染色）并行病理学评分。结果与Ns组及BML组各对应时相点比较，SAP组小鼠血清淀粉酶、CRP、TNF-α、IL-1β水平均显著增加（P〈0．05）；血清IL-10水平下降（P〈0．05）；胰腺H—E染色均符合SAP的表现；胰腺组织的病理学损伤评分亦均显著增高（P〈0．05）。与SAP组各对应时相点比较，SAP＋BML组小鼠血清AMY、CRP、TNF—α、IL—1β及胰腺的病理学损伤评分均明显降低（P〈0．05）；血清IL-10水平则增高（P〈0．05）；胰腺组织病理学改变亦较SAP组有所改善。结论BML-111预处理对蛙皮素诱导的小鼠重症急性胰腺炎具有一定的保护作用，这种作用可能与BML-111对促炎因子TNF-α、IL-lβ及抗炎因子IL一10的调节有关。

Objective To investigate the effects of BML-1/1 on severe acute pancreatitis （SAP） induced by cerulein with subsequent LPS administration in mice and its possible mechanisms. Methods 128 mice were randomly allocated to 4 equal groups： SAP group, BML-111 pretreatment group （SAP＋BML group）, the BM-111 control group （BML group）, and normal saline group （NS group）. Each group was randomly divided into 4 time units （3, 6, 12, 24-hour） with 8 mice in each time unit. Severe acute pancreatitis （SAP） was established by intraperitoneal injection of cerulein （50 tr g/kg） seven times at hourly intervals and Escherichia coli lipopolysaccharide （10 mg/kg） once after the last dose of cerulein immediately. BML-111 （1 mg/kg） was administered 1 hour before the first injection in SAP＋BML and BML group. Samples were taken at 3, 6, 12, and 24-hour after the last injection. Serum levels of amylase was assayed by P-nitrophenyl malt seven glycoside method, and CRP, TNF-α,IL-βand IL-10 were measured by enzyme linked immunosorbent assay （Elisa）. Histological score of the pancreas was evaluated. Results The findings revealed that injury of pancreas was typically induced by cerulein. BML-11 pretreatment significantly reduced the levels of serum amylase, CRP, TNF-α, IL-1β, and the pathologyl/injury scorees of the pancreas, which increased in the SAP group. The serum levels of IL-10 were markedly increased. Which decreased in the SAP group. Conclusion BML-111 may play a critical protective role onle induced by intraperitoneal injection of cerulein and Escherichia coli lipopolysaccharide （LPS）. The underlying mechanisms of protective role may be attributable to its anti-inflammatory effects throughregulation on TNF-α, IL-1β, and IL-10.