To compare the bronchodilating and antiinflammatory effects of oral racemic formoterol (rac-FMT) and (R,R)-formoterol (R,R-FMT). METHODS: The changes of lung resistance (RL), dynamic lung compliance (Cdyn), and the accumulation of inflammatory cells in bronchoalveolar lavage fluids (BALF) induced by ovalbumin aerosol in sensitized guinea pigs and mice were investigated in vivo. RESULTS: Mean value increase of RL and mean value reduction of Cdyn from 1 to 30 min after antigen challenge were up to 101%

The aim of this study was to investigate whether transforming growth factor-h1 (TGF-h1) could induce alveolar epithelial to mesenchymal transition (EMT) in vitro. Alveolar epithelial cells (AECs) from SD rats were isolated by elastase cell dispersion and IgG panning. Expression of a-smooth muscle actin (a-SMA) was assayed using Western blotting and immunostaining analysis. Morphological changes, the markers of epithelial cell (E-cadherin), and stress fiber by actin reorganization were detected by an indirect immunostaining. The contents of collagen I were determined by spectrophotometry. The levels of endogenous TGF-h1 were measured with ELISA. Incubation of AECs with TGF-h1 (0.1～10ng/mL) induced abundant expression of a-SMA protein, and a-SMA expression in AECs reached a plateau when TGF-h1 was N 3ng/mL. Furthermore, we found that TGF-h1 (3ng/mL) exposure of AECs induced an authentic EMT characterized by abundant expression of a-smooth muscle actin, transformation of myofibroblastic morphology, increased formation of stress fiber by actin reorganization, and loss of epithelial marker E-cadherin. Meanwhile, significant increase in the levels of collagen I from 32.0 F 6.6mg/g in control to 98 F 10.8mg/g in TGF-h1-treated group was found over a 72h incubation period. Moreover, following stimulated by TGF-h1 (3ng/mL), a marked and time-dependent increase in endogenous TGF-h1 released from AECs was observed. At time points 72h, TGFh1 release mounted to 3451pg/ml, which was much enough to induce EMT in vitro. These results demonstrated that AECs, under stimulation of TGF-h1, underwent a conversion process into myofibroblasts in vitro.

目的：研究硝普钠（SNP）与异丙肾上腺素（ISO）对犬气管平滑肌松弛作用是否存在协同关系，并分析协同的机制。方法：采用放射免疫分析法测定犬气管平滑肌环核苷酸量，并用磷酸二酯酶（PDE）同工酶抑制剂为工具分析SNP与ISO相互作用的机制。结果：SNP（1～100Lmol•L-1）增强ISO（30Lmol•L-1）对3Lmol•L-1乙酰甲胆碱预收缩的犬气管平滑肌的松弛作用。SNP（100Lmol•L-1） 与ISO（30Lmol•L-1）对犬气管平滑肌松弛的协同作用伴有气管平滑肌中CAMP积聚比SNP与ISO单独时分别增加112倍与014倍。PDEÍ 抑制剂扎普司特（3 Lmol•L-1）使SNP的气管平滑肌CGM P积聚由214倍增加到416倍，可进一步增加气管松弛作用112倍。合并PDEË抑制剂氰胍哒嗪（30Lmol•L-1）和PDEÌ抑制剂咯利普兰（30Lmol•L-1）或合并SNP（100Lmol•L-1） 和咯利普兰（30Lmol•L-1）均能进一步增强ISO的气管cAMP积聚与松弛作用。结论：SNP是通过气管平滑肌cGMP含量增加而抑制PDEË，导致SNP与ISO对气管松弛的协同作用。

human PDE4A was improved by ammonium sulfate fractionation, DEAE Sephadex A-50 chromatography, and Sephadex G-100 chromatography. The activity of PDE4A was measured by high performance liquid chromatography (HPLC). RESULTS: Induced PDE4A activity expressed in crude yeast cell GL62 supernatant and pellet was (340±21) nmol•g-1•min-1 and (250±25) nmol•g-1•min-1 respectively. The specific activity of recombinant PDE4A in supernatant was improved 6.4 fold. Ciclamilast, piclamilast, and rolipram could inhibit PDE4A activity. The IC50 values (95% confidence limits) of ciclamilast, piclamilast, and rolipram were 1.27 (0.84-1.91), 66.4 (33.3-132.2), and 3.73 (2.51-5.53) μmol/L respectively. Zaprinast, aspirin, and indomethacin had no obvious inhibitory effect on PDE4A activity. CONCLUSION: The specific activity of PDE4A expressed in yeast cell GL62 can be improved by ammonium sulfate fractionation, DEAE Sephadex A-50 chromatography, and Sephadex G-100 chromatography. Ciclamilast, piclamilast, and rolipram can inhibit PDE4A activity while zaprinast, aspirin, and indomethacin have no obvious inhibitory effect on PDE4A activity. Human PDE4A expressed in GL62 might be useful in the research and screening of new selective PDE4 inhibitors.

上皮完整或去上皮的豚鼠离体气管以300Lmol•L-1硝普钠（SNP）预处理1h，使SNP对抗乙醋甲胆碱气管收缩作用的剂量反应曲线右移1.3-1.5倍，最大舒张率下降41%-58%，形成SNP气管松弛作用的耐受性82溴环鸟苷酸可模拟SNP在豚鼠离体气管形成的SNP耐受性，谷胱甘肽（1mmol•L-1）及环核苷酸磷酸二酯酶（PDE）V抑制剂扎普司特（30Lmol•L-1）均可部分翻转SNP的气管松弛作用耐受性，而蛋白合成抑制剂环己酰亚胺（10Lmol•L-1）对SNP的耐受性无预防作用。结果表明SNP可产生豚鼠离体气管松弛耐受性，这可能是由于气管平滑肌中环鸟苷酸（CGMP）积聚而下调鸟苷酸环化酶（GC）活性和上调PDEÍ活性。