Tamaoki J, Kobayashi K, Sakai N, Kanemura T, Kawakami M, Takizawa T
Nihon Kyobu Shikkan Gakkai Zasshi. 1989 Sep;27(9):1040-5.
We studied the effect of indomethacin (INDO) inhalation therapy on patients with excessive sputum due to chronic respiratory infection. INDO (3.5 x 10(-2) M) reduced sputum production from 211 +/- 43 to 106 +/- 22 ml/day (p less than 0.05, n = 7), the effect that was more remarkable in patients with diffuse panbronchiolitis (DPB). The prostaglandin E2 (PGE2) levels in sputum were also decreased significantly. In addition, to elucidate the mechanism of action of INDO on epithelial ion transport, we measured short-circuit current (Isc) of canine tracheal epithelium in response to 3 x 10(-6) M INDO under short-circuit conditions in vitro. Addition of INDO to mucosal medium decreased Isc from 42.8 +/- 6.0 to 8.2 +/- 3.5 microA/cm2 (p less than 0.01, n = 6). The increases in Isc produced by PGE2 and PGF2 alpha were abolished by furosemide, a Cl-transport blocker. These results suggest that INDO inhalation is a promising therapy in improving excessive sputum production, and that this effect may be attributed to inhibition of PGE2-dependent Cl-secretion into the airway lumen.
我们研究了吲哚美辛(INDO)吸入疗法对慢性呼吸道感染所致痰液过多患者的影响。吲哚美辛(3.5×10⁻² M)可使痰液分泌量从211±43 ml/天降至106±22 ml/天(p<0.05,n = 7),该效果在弥漫性泛细支气管炎(DPB)患者中更为显著。痰液中前列腺素E2(PGE2)水平也显著降低。此外,为阐明吲哚美辛对上皮离子转运的作用机制,我们在体外短路条件下,测量了3×10⁻⁶ M吲哚美辛作用下犬气管上皮的短路电流(Isc)。向黏膜培养基中添加吲哚美辛可使Isc从42.8±6.0 μA/cm²降至8.2±3.5 μA/cm²(p<0.01,n = 6)。呋塞米(一种Cl⁻转运阻滞剂)可消除PGE2和PGF2α引起的Isc增加。这些结果表明,吲哚美辛吸入疗法在改善痰液过多分泌方面是一种有前景的治疗方法,且该作用可能归因于抑制了PGE2依赖的Cl⁻分泌至气道腔。