吡格列酮对大鼠急性坏死性胰腺炎的干预治疗作用

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目的观察经过氧化酶体增殖因子活化受体γ(PPARγ)配体吡咯列酮预处理后急性坏死型胰腺炎(SAP)大鼠胰腺组织中核因子-(?)B(NF-(?)B)和细胞间粘附分子-1(ICAM-1)表达的变化.探讨PPARγ对大鼠SAP的干预治疗作用。方法54只健康雄性Sprague-Dawley大鼠,均分为假手术组(C组)、SAP组(A组)和吡格列酮预处理组(Ⅰ组)。采用逆行胰胆管内加压注射5%牛磺胆酸钠(0.1 ml/100 g)建立SAP模型。Ⅰ组大鼠在术前2 h腹腔内注射吡格列酮(2 mg/100 g)。分别于术后3、6、12 h 3个时段采用腹主动脉放血法将大鼠分批处死(每次每组6只),取血、腹水和胰腺组织。采用免疫组化二步法检测胰腺组织NF-(?)B和ICAM-1的表达.同时进行血清淀粉酶、腹水、胰腺大体病理、组织学评分和胰腺组织含水量测定。结果吡咯列酮预处理可明显减轻大鼠SAP严重程度,血清淀粉酶水平于6 h后降低;腹水量减少;胰腺组织大体和病理评分6 h后降低;组织含水量逐渐减少。吡咯列酮预处理后大鼠胰腺组织中ICAM-1表达减弱、NF-(?)B活性受到抑制(P值均<0.05)。结论吡咯列酮具有减轻SAP效应.可能是通过抑制NF-(?)B活性和ICAM-1表达起到抗炎作用.有望成为一种临床治疗SAP的有效新方法。 Objective To observe the changes of nuclear factor - (?) B (NF -? B) in pancreas of acute necrotizing pancreatitis (SAP) rats pretreated with pyrrolizidine by the ligand of PPARγ, And intercellular adhesion molecule-1 (ICAM-1) expression in rats.ObjectiveTo investigate the therapeutic effect of PPARγ on SAP in rats. Methods Fifty - four healthy male Sprague - Dawley rats were randomly divided into sham operation group (C group), SAP group (Group A) and pioglitazone pretreatment group (Group Ⅰ). The SAP model was established by injecting 5% sodium taurocholate (0.1 ml / 100 g) into the pancreatic duct by means of retrograde cholangiopancreatography. Rats in group Ⅰ were injected intraperitoneally with pioglitazone (2 mg / 100 g) 2 h before surgery. Rats were sacrificed at 3, 6, and 12 h after operation by abdominal aorta bloodletting (6 in each group). Blood, ascites and pancreatic tissues were collected. The expression of NF -? B and ICAM - 1 in pancreas was detected by immunohistochemical two - step method. Serum amylase, ascites, gross pathology of pancreas, histological score and water content of pancreas were also measured. Results Pretreatment with pioglitazone significantly reduced the severity of SAP in rats. Serum amylase level decreased after 6 h. The amount of ascites decreased. The gross and pathological scores of pancreatic tissue decreased after 6 h. The water content in the tissues decreased gradually. After pretreatment with pioglitazone, the expression of ICAM-1 in pancreatic tissue decreased and the activity of NF -? B was inhibited (all P <0.05). Conclusion Pyrrolizidine can reduce the SAP effect, which may be an anti-inflammatory effect by inhibiting the activity of NF -? B and the expression of ICAM-1, which is expected to become a new effective method for the clinical treatment of SAP.
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