Zhao Hua, Chen Ji-Wei, Zhou Ya-Kui, Zhou Xue-Feng, Li Pei-Yun
Department of General Surgery, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, China.
World J Gastroenterol. 2003 Feb;9(2):338-41. doi: 10.3748/wjg.v9.i2.338.
To determine whether Platelet activating factor (PAF) has a regulation role in the expression of adhesion molecules and accumulation of neutrophils in a murine model of acute pancreatitis.
One hundred twenty-eight Kunming mice were divided into four groups. Group 1 received 0.1 ml saline s.c. every hour for three hours (sham). Group 2 received cerulein (50 microg/kg dose s.c.) every hour for three hours. Group 3 received AP and additional challenge of PAF (50 mg/kg in absolute ethanol) (AP/PAF). Group 4 received AP, plus therapeutic treatment with GAB (25 mg dose i.p.) immediately after the first challenge of cerulein (AP/GAB). Animals were sacrificed at 12 h after the first challenge of saline or cerulein. Adhesion molecules of pancreas were semi-quantified by SP methods. Standard assays were performed for serum amylase and myeloperoxidase activity (MPO) of pancreas. Histology of pancreas was scored in a blind manner. Water content of pancreas was also measured at the same time.
Control pancreata showed negligible adhesion molecule expression and neutrophil accumulation. There were evident adhesion molecules expression and neutrophil accumulation in AP and AP/PAF compared with sham (P<0.05). AP/GAB had a lower level of adhesion molecules, neutrophils, and water content versus AP and AP/PAF (P<0.05). Histology showed a trend toward improvement in AP/GAB, but did not reach statistical significance.
PAF can induce the expression of adhesion molecules that mediate neutrophil accumulation. The PAF antagonist reduces the expression of adhesion molecules and the severity of inflammation when given immediately after the induction of mild AP in mice. These results suggest that PAF antagonism may be useful in the treatment of mild pancreatitis after its clinical onset.
在急性胰腺炎小鼠模型中,确定血小板活化因子(PAF)对黏附分子表达及中性粒细胞聚集是否具有调节作用。
128只昆明小鼠分为四组。第1组每小时皮下注射0.1 ml生理盐水,共注射3小时(假手术组)。第2组每小时皮下注射蛙皮素(剂量为50微克/千克),共注射3小时。第3组先诱导急性胰腺炎(AP),随后额外给予PAF(50毫克/千克,溶于无水乙醇)(AP/PAF组)。第4组在首次注射蛙皮素后立即给予AP,并腹腔注射GAB(剂量为25毫克)进行治疗(AP/GAB组)。在首次注射生理盐水或蛙皮素后12小时处死动物。采用SP法对胰腺黏附分子进行半定量分析。对血清淀粉酶及胰腺髓过氧化物酶活性(MPO)进行标准检测。对胰腺组织学进行盲法评分。同时测量胰腺含水量。
对照组胰腺黏附分子表达及中性粒细胞聚集可忽略不计。与假手术组相比,AP组和AP/PAF组有明显的黏附分子表达及中性粒细胞聚集(P<0.05)。与AP组和AP/PAF组相比,AP/GAB组的黏附分子、中性粒细胞及含水量水平较低(P<0.05)。组织学检查显示AP/GAB组有改善趋势,但未达到统计学意义。
PAF可诱导介导中性粒细胞聚集的黏附分子表达。在小鼠轻度AP诱导后立即给予PAF拮抗剂,可降低黏附分子表达及炎症严重程度。这些结果表明,PAF拮抗作用可能对临床发病后的轻度胰腺炎治疗有用。