内皮素受体拮抗剂BQ123对大鼠急性坏死性胰腺炎E-、P-选择素表达的影响

Effects of BQ123 on expression of E-and P-selectin in mice with acute necrotic pancreatitis

目的观察急性坏死性胰腺炎(ANP)动物模型血管内皮细胞E-选择素和P-选择素(se-lectin)的变化特点以及用内皮素受体拮抗剂(ET-RA)BQ123治疗后的改变。方法54只SD大鼠随机分为3组:正常组(n=6),ANP组(n=24),BQ123治疗组(ANP+BQ123,n=24)。采用胰腺实质注射牛磺胆酸钠的方法制作ANP模型,制模后6h用BQ123进行治疗,监测制模后24h、48h、72h和7d血清淀粉酶活性;光镜下观察肺及胰腺组织白细胞浸润情况;免疫组化观察胰腺组织E-选择素、P-选择素表达;RT-PCR检测胰腺组织E-选择素、P-选择素mRNA变化。结果ANP组肺及胰腺内大量白细胞浸润,而BQ123治疗组白细胞明显减少。ANP组胰腺选择素表达水平显著高于正常组水平,而BQ123治疗组较ANP组显著降低。结论内皮素受体拮抗剂可通过调控ANP时选择素的表达水平,达到减少白细胞在局部器官浸润,保护器官功能的效果。

Objectives To examine changes of E and P-selectin in mice with acute necrotic pancreatitis （ANP） and the effects of BQ123 on them. Methods 54 SD mice were assigned to 3 groups randomly, including normal control （n = 6）, ANP group （n = 24）, and BQ123 （Endothelin Receptor Antagonist, ET-RA group, n = 24）. ANP was induced by intrapancreatic injection of 5% sodium tauroeholate （2.5 ml/kg）. BQ123 was administered subcutaneously at a dose of 12.5 μg/kg per 6 h at 6 h following sodium taurocholate injection. Serum amylase was measured at 24 h, 48 h, 72 h and 7 d after sodium taurocholate injection. Pathological alteration in the pancreas was studied. Leukocytic infiltrate in the pancreas and lungs was observed under an optic-microscope. Expressions of E- and P- selectin were evaluated by inmmunohistochemistry and RT-PCR. Results The levels of leukocytic infiltrate and E- and P-selectin in ANP group were significantly higher than those in control group （P 〈 0.01）. After treatment with BQ123, the levels of leukocytic infiltrate and E and P-selectin decreased significantly （P 〈 0. 01 ）. Conclusions ET-RA can decrease leukocytic infiltrate and protect organ functions of mice with ANP by down-regulating expression of selectins.