Saruç Murat, Yuceyar Hakan, Turkel Nurten, Ozutemiz Omer, Tuzcuoglu Isil, Ayhan Semin, Yuce Gul, Coker Isil, Huseyino Afik
Department of Gastroenterology, Celal Bayar University, Manisa, Turkey.
Med Sci Monit. 2007 Mar;13(3):BR67-72.
The aim was to reveal the mechanism of hemolysis-induced acute pancreatitis and to evaluate the role of heme and heme oxygenase activity in inducing pancreatic inflammation in an experimental hemolysis model.
MATERIAL/METHODS: Hemolytic anemia was induced in rats by intraperitoneal injection of 60 mg/kg acetylphenylhydrazine (APH). To evaluate the toxic effect of free heme after hemolysis, heme oxygenase inhibitor (HOI) was used to inhibit the enzyme which decreases the free heme concentration after hemolysis. One hundred and fifty rats were divided into two treatment and three control groups. Rats in the hemolysis group were given APH intraperitoneally. Rats in the HOI+hemolysis group were given Cr(III)mesoporphyrin IX chloride as HOI and then APH intraperitoneally. Serum amylase and lipase levels as well as pancreatic tissue cytokine content were determined and histological examination performed.
No hemolysis or pancreatitis was seen in the control groups. Massive hemolysis was seen in 22 of the 30 rats of the hemolysis group and 20 of the 30 rats of the HOI+hemolysis group. The total pancreatitis rates were 60% and 76.6% in the hemolysis and HOI+hemolysis groups, respectively (p<0.05). Pancreatic cytokine levels were significantly higher in the HOI+hemolysis and hemolysis groups than in all control groups. The highest ICAM-1 and MCP-1 levels were in the HOI+hemolysis group. Histological signs of acute pancreatitis were also more severe in this group.
Acute massive hemolysis can induce acute pancreatitis. Excess of free vascular heme seems to be an inducer of inflammation by modulating ICAM-1 and MCP-1.
目的是揭示溶血诱导的急性胰腺炎的机制,并评估血红素和血红素加氧酶活性在实验性溶血模型中诱导胰腺炎症的作用。
材料/方法:通过腹腔注射60mg/kg乙酰苯肼(APH)诱导大鼠发生溶血性贫血。为了评估溶血后游离血红素的毒性作用,使用血红素加氧酶抑制剂(HOI)抑制该酶,该酶可降低溶血后的游离血红素浓度。150只大鼠分为两个治疗组和三个对照组。溶血组大鼠腹腔注射APH。HOI+溶血组大鼠先腹腔注射氯化铬(III)中卟啉IX作为HOI后再注射APH。测定血清淀粉酶和脂肪酶水平以及胰腺组织细胞因子含量,并进行组织学检查。
对照组未见溶血或胰腺炎。溶血组30只大鼠中有22只出现大量溶血,HOI+溶血组30只大鼠中有20只出现大量溶血。溶血组和HOI+溶血组的总胰腺炎发生率分别为60%和76.6%(p<0.05)。HOI+溶血组和溶血组的胰腺细胞因子水平显著高于所有对照组。HOI+溶血组的ICAM-1和MCP-1水平最高。该组急性胰腺炎的组织学征象也更严重。
急性大量溶血可诱发急性胰腺炎。游离血管血红素过量似乎通过调节ICAM-1和MCP-1成为炎症诱导因素。