Wittel Uwe A, Singh Ajay P, Henley Brandon J, Andrianifahanana Mahefatiana, Akhter Mohammed P, Cullen Diane M, Batra Surinder K
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha 68198-5870, USA.
Pancreas. 2006 Nov;33(4):364-70. doi: 10.1097/01.mpa.0000240601.80570.31.
Little is known about the molecular and biological aspects of the epidemiological association between smoking and pancreatic pathology, such as chronic pancreatitis and pancreatic cancer. Recently, we reported that tobacco smoke exposure induced morphological alterations in the rat pancreas. Here, we have investigated the alterations in the expression of genes associated with exocrine pancreatic function and cellular differentiation upon exposure to cigarette smoke.
Female rats were exposed to environmental smoke inhalation for 2 d/wk (70 min/d) for 12 weeks. The expression profiles of trypsinogen, pancreas-specific trypsin inhibitor, cholecystokinin A receptor, cystic fibrosis transmembrane conductance regulator (CFTR), carbonic anhydrase, and Muc1 and Muc4 mucins transcripts were analyzed by RNA slot blot analysis. Muc4 expression was also examined by immunohistochemistry.
Our data revealed that the ratio of trypsinogen to that of the protective pancreas-specific trypsin inhibitor was elevated upon cigarette smoke exposure. The expression of carbonic anhydrase and CFTR remained unaltered when inflammatory signs were not detected in histological examinations. On the other hand, when pancreatic inflammation was present, the levels of CFTR and carbonic anhydrase were increased, indicating ductal and/or centroacinar cell involvement. No changes in the expression of Muc1 and Muc4 mucins were observed.
Our data show that cigarette smoke exposure leads to an increased vulnerability to pancreatic self-digestion. Moreover, the concomitant involvement of pancreatic ducts occurs only when focal pancreatic inflammation is present.
关于吸烟与胰腺病理（如慢性胰腺炎和胰腺癌）之间流行病学关联的分子和生物学方面，我们了解甚少。最近，我们报道了烟草烟雾暴露会导致大鼠胰腺出现形态学改变。在此，我们研究了暴露于香烟烟雾后与胰腺外分泌功能和细胞分化相关基因表达的变化。
雌性大鼠每周暴露于环境烟雾中2天（每天70分钟），持续12周。通过RNA斑点印迹分析来检测胰蛋白酶原、胰腺特异性胰蛋白酶抑制剂、胆囊收缩素A受体、囊性纤维化跨膜传导调节因子（CFTR）、碳酸酐酶以及Muc1和Muc4粘蛋白转录本的表达谱。还通过免疫组织化学检查Muc4的表达情况。
我们的数据显示，暴露于香烟烟雾后，胰蛋白酶原与具有保护作用的胰腺特异性胰蛋白酶抑制剂的比例升高。在组织学检查未检测到炎症迹象时，碳酸酐酶和CFTR的表达保持不变。另一方面，当出现胰腺炎症时，CFTR和碳酸酐酶的水平升高，表明导管和/或腺泡中心细胞受到影响。未观察到Muc1和Muc4粘蛋白表达的变化。
我们的数据表明，暴露于香烟烟雾会增加胰腺自我消化的易感性。此外，仅当存在局灶性胰腺炎症时，胰腺导管才会同时受到影响。
