ROLE OF ALVEOLAR EPITHELIUM AND AIRWAY EPITHELIUM IN ACUTE LUNG INJURY MODEL : CYTOKINES PRODUCTION AND EPITHELIUM INJURY

[研究1]在急性肺损伤中，肺泡和气道上皮细胞是损伤的目标。另一方面，上皮细胞通过产生各种介质和生长因子在急性肺损伤的发病机制中起重要作用。本研究的目的是阐明由上皮细胞产生的介质，并评估各种药物对介质的影响。腹腔注射内毒素（10 mg/kg），造成大鼠急性肺损伤。免疫组化法检测诱导型一氧化氮合酶（iNOS）、硝基酪氨酸（nTyr）、肿瘤坏死因子-α（TNF-α）和生长调节癌基因（GRO/CINC）的蛋白表达。通过肺湿/干重比和支气管肺泡灌洗液（BALF）中的中性粒细胞计数来量化急性肺损伤。评估了利多卡因（2 mg/kg/hr）、氯胺酮（10 mg/kg/hr）和异丙酚（20 mg/kg/hr）的影响。内毒素后3-6小时，在肺泡II型肺细胞中观察到iNOS、nTyr和GRO/CINC的蛋白表达。李 ...更多信息 多卡因、氯胺酮和丙泊酚减弱了这些蛋白质的表达。这些药物也减弱肺湿/干重比和BALF中的中性粒细胞在内毒素处理的大鼠中发现的增加。[研究2]在急性肺损伤的恢复和肺纤维化的预防过程中，II型肺细胞的增殖是一个先决条件。众所周知，角质细胞生长因子（KGF）和肝细胞生长因子（HGF）促进II型细胞的增殖。本研究的目的是评估各种药物对肺泡II型上皮细胞增殖的影响。从大鼠肺中分离并培养II型肺细胞。我们评估了氯胺酮，利多卡因，和咯利普兰，IV型磷酸二酯酶的选择性抑制剂对增殖的II型细胞在KGF或HGF的存在和不存在的影响。氯胺酮和利多卡因没有效果。这些药物未能增强KGF/HGF诱导的促进II型细胞增殖。Rolipram在生长因子不存在的情况下成功地增强了II型肺细胞的增殖，并且进一步增加了KGF/HGF对II型细胞增殖的增强。少

[Study 1] In acute lung injury, alveolar and airway epithelial cells are target for insult. On the other hand, the epithelium plays an important role in the pathogenesis of acute lung injury by producing various mediators and growth factors. The aim of the current study was to elucidate mediators produced by the epithelium and assess the effects of various drugs on mediators. Acute lung injury was induced by intraperitoneal endotoxin (10 mg/kg) in rats. Protein expression of inducible nitric oxide synthase (iNOS), nitrotyrosine (nTyr), tumor necrosis factor-α (TNF-α), and growth regulated oncogene (GRO/CINC) was immunohistochemically evaluated. Acute lung injury was quantified by lung wet/dry weight ratio and neutrophil counts in bronchoalveolar lavage fluid (BALF). The effects of lidocaine (2 mg/kg/hr), ketamine (10 mg/kg/hr), and propofol (20 mg/kg/hr) were assessed. Protein expression of iNOS, nTyr, and GRO/CINC was observed in alveolar type II pneumocytes 3-6 hr after endotoxin. Li … More docaine, ketamine, and propofol attenuated expression of these proteins. These drugs also attenuated increase in lung wet/dry weight ratio and neutrophils in BALF found in endotoxin-treated rats.[Study 2] In process of recovery from acute lung injury and prevention of pulmonary fibrosis, proliferation of type II pneumocytes is a prerequisite. Keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF) are well known to promote proliferation of the type II cells. The aim of the current study was to assess the effects of various drugs on proliferation of alveolar type II epithelial cells. Type II pneumocytes were isolated from rats' lungs and cultured. We assessed the effects of ketamine, lidocaine, and rolipram, a selective inhibitor of the type IV phosphodiesterase on proliferation of type II cells in the presence and absence of KGF or HGF. Ketamine and lidocaine had no effect. These drugs failed to enhance KGF/HGF-induced promotion of type II cell proliferation. Rolipram successfully enhanced proliferation of type II pneumocytes in the absence of the growth factors, and furthermore increased enhancement of type II cells proliferation by KGF/HGF. Less