中文摘要：

目的探讨磷酸二酯酶4（PDFA）抑制剂YM976对丙烯醛诱导的大鼠气道黏蛋白高分泌的影响及其作用机制。方法将48只SD大鼠随机平均分为6组，其中4组以雾化吸人丙烯醛的方法制备气道黏液高分泌模型并分为不予YM976干预的丙烯醛模型组和制模期间给予低、中或高剂量YM976干预组；另2组中，1组为正常对照组；1组为YM976对照组。取各组大鼠肺组织，以阿辛蓝一过碘酸雪夫（AB—PAS）染色检测黏蛋白的表达，免疫组织化学染色和蛋白质印迹法检测黏蛋白Muc5ac蛋白表达，反转录PCR检测Muc5ac mRNA表达，并取支气管肺泡灌洗液（BALF），以酶联免疫吸附试验（ELISA）检测BALF上清液中肿瘤坏死因子α（TNF-α）、细胞因子诱导的中性粒细胞趋化物1（CINC-1）浓度。结果丙烯醛模型组和低、中、高剂量YM976干预组大鼠肺组织AB-PAS阳染面积（分别为23．65±2．86、22．63±2．12、16．34±1．72、5．03±0．72）、Muc5ac免疫组织化学染色积分吸光度值（分别为0．54±0．05、0．49±0．06、0．32±0．04、0．22±0．04）、Muc5ae蛋白表达积分吸光度值（分别为1．177±0．190、0．806±0．180、0．303±0．061、0．134±0．035）、Muc5ac mRNA表达积分吸光度值（分别为0．246±0．021、0．223±0．020、0．161±0．012、0．097±0．011）以及BALF中TNF-α浓度[分别为（96．77±2．31）、（87．65±2．75）、（73．56±2．62）、（52．23±2．79）μg/L]、CINC-1浓度[分别为（145．75±4．43）、（139．73±5．51）、（95．34±5．13）、（65．74±5．62）μg/L]均明显高于正常对照组[分别为4．38±0．32、0．12±0．02、0．058±0．024、0．061±0．006、（18．23±2．32）μg/L、（33．56±3．43）μg/L，均P〈0．05]，但中、高剂量YM976干预组均明显低于丙烯醛模型组（均P〈0．05）。结论PDE4抑制剂YM976可能通过抑制炎症趋化因子TNF-α、CINC-1的释放而抑制丙烯?

英文摘要：

Objective To examine the effects of YM976, a phosphodiesterase （PDE） 4 inhibitor, on muein hypersecretion of airway stimulated with aerolein. Methods Forty-eight SD rat were randomly divided into 6 equal groups. Twenty-four rats underwent gastric perfusion of YM976 0.5, 1.5, or 4.5 mg · kg^- 1 · d^-1 （ n = 8 for each group） and then underwent aerosol inhalation of 3.0 ppm acrolein 6 hours per day for 12 days so as to establish rat models of airway mucus hyperseeretion. Eight rats underwent aerosol inhalation of 3.0 ppm acrolein only for 12 days to establish rat models of airway mucus hypersecretion without any drug intervention （aerolein model group）. Eight rats underwent gastric perfusion of 5% methylcellulose and then acrolein inhalation for 12 days （methylcellulose group）, and another 8 rats underwent gastric perfusion of YM976 4.5 mg/kg once a day and then inhalation of normal saline for 12 days （ YM976 control group）. On the 13th day the rats were killed. Bronchoalveolar lavage fluid （BALF） was acquired for cell count, and ELISA was used to detect the levels of tumor necrosis factor （TNF）-α and cytokine-induced neutrophil chemoattractant （CINC）-1 in the BALF. The mucin level in the airway mucous membrane was detected by alcian blue （AB）/periodic acid-Schiff （PAS） method. Muc5ac protein was measured by immunohistochemieal staining and Western-blotting, and MucSac mRNA was detected by RT-PCR. Results The percentages of positive AB/PAS staining of the acrolein model group and the 3 YM976 groups （0.5, 1. 5, and 4.5 mg · kg^-1 · d^-1） were 23.65 ±2.86, 22.63±2. 12, 16.34±1.72, and 5.03±0.72 respectively. The integral optical density （IOD） levels of Muc5ac immunohistochemical staining of the methylcellulose group and the 3 YM976 groups were 0.54 ± 0.05, 0.49 ± 0.06, 0.32 ± 0.04, and 0.22 ± 0.04 respectively. The IOD of Muc5ac protein expression by Western-blotting of the methylcellulose group and the 3 YM976 groups were 1. 177± 0. 190, 0. 806± 0. 180,