Pancreatic elastase activates pulmonary nuclear factor kappa B and inhibitory kappa B, mimicking pancreatitis-associated adult respiratory distress syndrome

BACKGROUND: Select pancreatic enzymes, primarily elastase, precipitate pulmonary injury similar to pancreatitis-associated adult respiratory distress syndrome and stimulate leukocyte cytokine production in vitro via nuclear factor kappa B (NF-kappaB) activation. This study explores the effect of systemic pancreatic enzymes on pulmonary NF-kappaB and inhibitory kappa B (IkappaB) proteins and their role in enzyme-induced pulmonary injury. METHODS: Mice received pancreatic elastase, amylase, lipase, or trypsin intraperitoneally. Bronchoalveolar lavage IkappaBalpha/IkappaBbeta proteins were measured by immunoblot. Pulmonary NF-kappaB activation, tumor necrosis factor (TNF) gene expression, and neutrophil infiltration (myeloperoxidase) were determined and myeloperoxidase experiments repeated in p55 TNF receptor-deficient (TNF KO) animals. Additional animals received pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-kappaB activation, and TNF protein and pulmonary microvascular permeability were measured after elastase administration. RESULTS: Pancreatic elastase induced pulmonary IkappaBalpha/IkappaBbeta degradation (30 minutes), NF-kappaB activation (60 minutes), and TNF gene expression (60 minutes) with subsequent neutrophilic inflammation (4 hours) and microvascular leakage (24 hours), whereas amylase, lipase, and trypsin did not. Furthermore, lung injury was markedly reduced in TNF KO animals and PDTC significantly attenuated TNF production and pulmonary microvascular leakage. CONCLUSIONS: Pancreatic elastase induces cytokine-mediated lung injury and this pathway involves the NF-kappaB second messenger system, further supporting elastase as a factor linking pancreatic inflammation to systemic illness during severe acute pancreatitis.     

人乙型肝炎病毒x基因转基因小鼠模型的建立

目的 建立人乙型肝炎病毒ｘ（ＨＢｘ）基因转基因小鼠模型。方法 用显微注射法制备转基因小鼠,用分子杂交法鉴定转基因小鼠ＨＢｘ的整合与表达。结果 建立了人ＨＢｘ的基因转基因小鼠模型。经Ｓｏｕｔｈｅｒｎ杂交鉴定得到１７只转基因首建鼠。逢肝脏提取总ＲＮＡ进行Ｎｏｒｔｈｅｒｎ杂交,结果显示１７只首建鼠肝脏中均有ＨＢｘ表达。结论 为从整体水平研究慢性乙肝炎患者诱发肝癌的作用机制及ＨＢｘ的反式激活作用机制提供了     

弹性蛋白酶损伤肺致炎的地鼠血清中一氧化氮和肿瘤坏死 …

目的 观察由弹性蛋白酶损伤肺致炎的地鼠血清中一氧化氮（ＮＯ）和肿瘤坏死因子（ＴＮＦ－α）的动态变化,并初步探讨两者在炎症中的作用。方法 建立弹性蛋白酶损伤肺致炎金黄地鼠模型,用组化和免疫组化方法检测气道上皮细胞和肺内单核巨噬细胞一氧化氮合酶活性,测定血清中ＮＯ和ＴＮＦ－α的动态变化。结果 弹性蛋白酶损伤肺致炎地鼠气道上皮细胞和肺内单核巨噬细胞ＮＯＳ活性明显加强,在炎症早期血清中ＮＯ和ＴＮＦ－α含量     

N-甲基-D-天门冬氨酸受体及其调控的钙内流在大鼠感染性脑损伤中的变化

为探讨Ｎ－甲基－Ｄ－天门冬氨酸（ＮＭＤＡ）受体及其调控的钙内流在感染性脑损伤发病机制中的作用，采用Ｆｕｒａ－２／Ａｍ荧光法检测大鼠大脑皮质突触体内游离钙浓度（［Ｃａ＋＋］ｉ）。结果表明，注射百日咳杆菌组的［Ｃａ＋＋］ｉ较对照组显著增加（Ｐ均＜０．０１），并与注菌时间呈正相关关系（４小时ｖｓ０．５小时和２４小时ｖｓ４小时，Ｐ＜０．０５和＜０．０１）。ＮＭＤＡ受体的非竞争性拮抗剂ＭＫ－８０１预处理组（ＭＢＰ）的［Ｃａ＋＋］ｉ、脑含水量和伊文思蓝含量均较注菌组显著减少（Ｆ值分别为７２．２５、１６．８９、１４．３６，Ｐ＜０．０１和＜０．０５），并以２４小时［Ｃａ＋＋］ｉ减少最为明显（Ｐ＜０．０１）。提示ＮＭＤＡ受体调控的神经元内钙超载在感染性脑损伤、尤其在迟发性脑损伤的发病机制中起着重要作用。     

经蝶窦显微手术治疗垂体侵袭性腺瘤

为总结临床经验，报告经蝶窦进路显微手术治疗垂体侵袭性腺瘤１８例，其中４例伴有胰岛素依赖型糖尿病。施肿瘤近全切除１５例，大部分切除３例，术后追加放射治疗１０例，服用溴隐亭治疗５例，术后平均随访３．８年，其中３例（１６．６％）平均１．６年复发，二次比额手术治愈，就垂体侵袭性和伴有胰岛素依赖型糖尿病患者经蝶窦显微手术治疗的可行性进行探讨。