THERAPY FOR ACUTE LUNG INJURY : TARGET FOR TYPE II ALVEOLAR EPITHELIAL CELLS

在急性肺损伤恢复和预防肺纤维化的过程中，II型肺泡上皮细胞的增殖是先决条件。在本研究中，我们主要评估了罗利普兰（PDE-IV抑制剂）和麻醉剂（异丙酚、咪达唑仑、氯胺酮和利多卡因）对II型细胞增殖和凋亡的影响。(1)从大鼠肺中分离ⅱ型肺细胞并进行培养。我们评估了氯胺酮、利多卡因、咪达唑仑、异丙酚和罗利普兰在存在和不存在KGF或HGF的情况下对II型细胞增殖的影响。氯胺酮和利多卡因无效。这些药物未能增强KGF/ hgf诱导的II型细胞增殖。在缺乏生长因子的情况下，罗利普兰成功地增强了II型肺细胞的增殖，并进一步增强了KGF/HGF对II型细胞增殖的增强作用。腹腔注射罗利普兰的小鼠肺ⅱ型细胞对BrdU的摄取增加。(2)罗利普兰、异丙酚、咪达唑仑、氯胺酮和利多卡因对培养成纤维细胞增殖无影响（JTC-19）。(3) Northern blotting证实，罗利普兰增加了培养的II型细胞SP-B mRNA的表达。(4)大鼠内毒素所致急性肺损伤的病理及生化变化，经上述药物预处理均可明显减轻。

In process of recovery from acute lung injury and prevention of pulmonary fibrosis, proliferation of type II alveolar epithelial cells is a prerequisite. In the current study, we mainly assessed the effects of rolipram, a PDE-IV inhibitor, and anesthetics (propofol, midazolam, ketamine, and lidocaine) on the type II cells proliferation and apoptosis. (1) Type II pneumocytes were isolated from rats' lungs and cultured. We assessed the effects of ketamine, lidocaine, midazolam, propofol, and rolipram 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.BrdU uptake by the type II cells was increased in the lung of mice receiving intraperitoneal rolipram. (2) Rolipram, propofol, midazolam, ketamine, and lidocaine had no effect on proliferation of cultured fibroblasts (JTC-19). (3) Rolipram increased expression SP-B mRNA in cultured type II cells as evidenced by Northern blotting. (4) In rats, pretreatment with these drugs successfully attenuated pathological and biochemical changes in acute lung injury induced by endotoxin.