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Cyclooxygenase-2在急性胰腺炎大鼠肺微循环障碍中的作用 被引量:1

Role of Cyclooxygenase-2 in Pulmonary Microcirculation Disorder in Rats with Acute Pancreatitis
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摘要 目的初步探讨急性胰腺炎大鼠肺组织Cyclooxygenase-2(Cox-2)的表达及其在急性胰腺炎肺微循环障碍中的作用。方法逆行胰胆管注射灭菌的4%牛磺胆酸钠诱导Sprague-Dawley大鼠急性出血坏死性胰腺炎(AHNP)模型。实验随机分为假手术组、AHNP组及Celecoxib预处理组,术后3、6、12和24h处死动物,取肺组织HE染色进行肺损伤的组织学评价,Mallory氏磷钨酸苏木精染色观察血管中的纤维素性血栓,免疫组化检测Cox-2蛋白表达。结果AHNP组肺组织Cox-2表达和病理学评分进行性增加,两者呈正相关(r=0.503,P=0.012)。在AHNP早期就可发现肺组织微血栓形成,其密度和损伤评分亦呈正相关(r=0.604,P=0.004);Celecoxib预处理在各时相点均减轻了肺损伤的程度、微血栓密度和Cox-2的表达水平(P<0.05);Celecoxib下调Cox-2表达程度与其改善肺组织病理损伤强度正相关,而与其降低微血栓形成的程度无明显相关性。结论肺微血栓形成所致的肺微循环障碍可能是诱导肺损伤发生的早期事件,并可能是始动因素;Cox-2过表达可能具有促凝血活性而在肺微血栓形成中扮演关键角色。 ObJective To identify the expression of Cyclooxygenase-2 (Cox-2)in lung tissues and its potential role in pulmonary microcirculation disorder in rats with acute pancreatitis. Methods The acute hemorrhagic and necrotic pancreatitis (AHNP) model was induced by the standard retrograde infusion of biliopancreatic duct with 4% sterile sodium taurocholate solution in Sprague-Dawley rats. The rats were randomly allocated into sham surgery group, AHNP group, and prophylactic celecoxih treated AHNP (C+ AHNP) group. The HE, phosphotungstic acid hematain (PTAH) and immunohistochemistrical (IHC) staining were employed to assess the dynamical alterations and interrelations of the histopathology, density of micro-thrombus and Cox-2 expression of lung tissue respectively over a time course of 3, 6, 12 and 24 hours. Results A significant and progressing increase in histopathologic scoring and Cox-2 expression in the lung tissues were found. There was a positive correlation between the Cox-2 expression and the histopathological scoring. A significant increase of pulmonary micro-thrombosis was detected at the early stage of the rat AHNP induced by sodium taurocholate, and the density of micro-thrombus was positively associated with the histopathological scoring. The prophylactic treatment with celecoxib, a highly selective inhibitor of Cox-2, attenuated the changes in histopathology, pulmonary micro-thrombosis and Cox-2 expression (P 〈 0. 05). The down-regulated intensity of the Cox-2 expression by celecoxib was positively correlated with the improvement of the histopathology injury, but not with the change of the pulmonary micro-thrombosis. Conclusion The pulmonary microcirculation dysfunction caused by micro-thrombosis is an early event or even an enabler of the development of APALI. The over-expression of Cox-2 may have promoted the procoagulant activity which plays a key role in the development of pulmonary thrombus.
出处 《四川大学学报(医学版)》 CAS CSCD 北大核心 2007年第2期250-254,共5页 Journal of Sichuan University(Medical Sciences)
关键词 胰腺炎 急性出血坏死性 肺损伤 血栓 环氧合酶2 CELECOXIB Pancreatitis, acute hemorrhagic and necrotic Lung injury Thrombus Cyclooxygenase-2 Celecoxib
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