Xu Ping, Zhou Xiao-Jiang, Chen Ling-Quan, Chen Jiang, Xie Yong, Lv Long-Hua, Hou Xiao-Hua
Department of Gastroente-rology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China.
World J Gastroenterol. 2007 Apr 7;13(13):1983-8. doi: 10.3748/wjg.v13.i13.1983.
To determine the effect of pioglitazone, a specific peroxisome proliferator-activated receptor-gamma (PPARgamma) ligand, on development of severe acute pancreatitis (SAP) and expression of nuclear factor-kappa B (NF-kappaB) and intercellular adhesion molecule-1 (ICAM-1) in the pancreas.
Male Sprague-Dawley (SD) rats (160-200 g) were randomly allocated into three groups (n = 18 in each group): severe acute pancreatitis group, pioglitazone group, sham group. SAP was induced by retrograde infusion of 1 mL/kg body weight 5% sodium taurocholate (STC) into the biliopancreatic duct of male SD rats. Pioglitazone was injected intraperitoneally two hours piror to STC infusion. Blood and ascites were obtained for detecting amylase and ascitic capacity. Pancreatic wet/dry weight ratio, expression of NF-kappaB and ICAM-1 in pancreatic tissues were detected by immunohistochemical staining. Pancreatic tissue samples were stained with hematoxylin and eosin (HE) for routine optic microscopy.
Sham group displayed normal pancreatic structure. SAP group showed diffuse hemorrhage, necrosis and severe edema in focal areas of pancreas. There was obvious adipo-saponification in abdominal cavity. Characteristics such as pancreatic hemorrhage, necrosis, severe edema and adipo-saponification were found in pioglitazone group, but the levels of those injuries were lower in pioglitazone group than those in SAP group. The wet/dry pancreatic weight ratio, ascetic capacity, serum and ascitic activities of anylase in the SAP group were significantly higher than those in the sham group and pioglitazone group respectively (6969.50 +/- 1368.99 vs 2104.67 +/- 377.16, 3.99 +/- 1.22 vs 2.48 +/- 0.74, P < 0.01 or P < 0.05). According to Kusske criteria, the pancreatic histologic score showed that interstitial edema, inflammatory infiltration, parenchyma necrosis and parenchyma hommorrhage in SAP group significantly differed from those in the sham group and pioglitazone group (7.17 +/- 1.83 vs 0.50 +/- 0.55, 7.67 +/- 0.82 vs 6.83 +/- 0.75, P < 0.01, P < 0.05. The expression of NF-kappaB and ICAM-1 in sham group was lower than that in SAP group and pioglitazone group (0.50 +/- 0.55 vs 33 +/- 1.21, P < 0.01). There was a significant difference in the expression of NF-kappaB and ICAM-1 between SAP group and pioglitazone group (7.50 +/- 1.05 vs 11.33 +/- 1.75, 0.80 +/- 0.53 vs 1.36 +/- 0.54, P < 0.01 or P < 0.05) at 12 h after the induction of pancreatitis.
Pioglitazone attenuates the severity of SAP. The beneficial effect of pioglitazone is multifactorial due to its anti-inflammatory activities, most likely through the inhibition of ICAM-1 expression and NF-kappaB activation. Specific ligands of PPARgamma may represent the novel and effective means of clinical therapy for SAP.
确定吡格列酮（一种特异性过氧化物酶体增殖物激活受体γ（PPARγ）配体）对重症急性胰腺炎（SAP）发展以及胰腺中核因子κB（NF-κB）和细胞间黏附分子-1（ICAM-1）表达的影响。
将雄性Sprague-Dawley（SD）大鼠（160 - 200 g）随机分为三组（每组n = 18）：重症急性胰腺炎组、吡格列酮组、假手术组。通过向雄性SD大鼠胆胰管逆行注入1 mL/kg体重的5%牛磺胆酸钠（STC）诱导SAP。在注入STC前两小时腹腔注射吡格列酮。采集血液和腹水检测淀粉酶及腹水量。采用免疫组织化学染色检测胰腺组织的湿/干重比、NF-κB和ICAM-1的表达。胰腺组织样本用苏木精和伊红（HE）染色进行常规光学显微镜检查。
假手术组胰腺结构正常。SAP组胰腺局部区域出现弥漫性出血、坏死和严重水肿。腹腔有明显的脂肪皂化。吡格列酮组也出现了胰腺出血、坏死、严重水肿和脂肪皂化等特征，但吡格列酮组这些损伤程度低于SAP组。SAP组胰腺湿/干重比、腹水量、血清和腹水淀粉酶活性分别显著高于假手术组和吡格列酮组（6969.50±1368.99 vs 2104.67±377.16，3.99±1.22 vs 2.48±0.74，P < 0.01或P < 0.05）。根据Kusske标准，胰腺组织学评分显示SAP组的间质水肿、炎症浸润、实质坏死和实质出血与假手术组和吡格列酮组有显著差异（7.17±1.83 vs 0.50±0.55，7.67±0.82 vs 6.83±0.75，P < 0.01，P < 0.05）。假手术组NF-κB和ICAM-1的表达低于SAP组和吡格列酮组（0.50±0.55 vs 33±1.21，P < 0.01）。胰腺炎诱导后12小时，SAP组和吡格列酮组NF-κB和ICAM-1的表达有显著差异（7.50±1.05 vs 11.33±1.75，0.80±0.53 vs 1.36±0.54，P < 0.01或P < 0.05）。
吡格列酮可减轻SAP的严重程度。吡格列酮的有益作用是多因素的，归因于其抗炎活性，很可能是通过抑制ICAM-1表达和NF-κB激活。PPARγ的特异性配体可能代表了SAP临床治疗的新型有效手段。
