Ito M, Suwabe A, Suzuki T, Tominaga M, Takahashi K
Department of Laboratory Medicine, Yamagata University School of Medicine.
Nihon Kyobu Shikkan Gakkai Zasshi. 1997 Nov;35(11):1163-72.
We investigated whether artificial surfactant modified pulmonary fibrosis following the intratracheal administration of bleomycin (BLM 3.75 mg/kg) in rats. Twenty-four hours after the administration of bleomycin, the lungs were washed twice with surfactant-TA (S-TA, 1 mg/ml, 6 ml x 2 times), and replaced with 0.5 ml of 10 mg/ml S-TA. Fourteen days later the animals were sacrificed and the lungs were assayed for collagen content and pathologic changes. BLM-treated rats showed both increases in wet lung weights and lung collagen content, and a loss in body weights (due to lung injury and fibrosis), but these changes were significantly inhibited by the intratracheal administration of S-TA. In vitro studies demonstrated that S-TA inhibited lung fibroblast proliferation in a dose dependent manner (0.01-0.5 mg/ml). This inhibition was also seen in native rat lung surfactant and its protein and lipid components. However, S-TA, did not change the number of rat type II pneumocutes in culture, and likely protected type II cells from dedifferentiation. S-TA inhibited BLM-induced pulmonary fibrosis, probably by directly inhibiting lung fibroblast proliferation.
我们研究了在大鼠气管内给予博来霉素(BLM 3.75mg/kg)后,人工表面活性剂是否能改善肺纤维化。给予博来霉素24小时后,用表面活性剂-TA(S-TA,1mg/ml,6ml×2次)对肺进行两次冲洗,然后注入0.5ml 10mg/ml的S-TA。14天后处死动物,对肺进行胶原蛋白含量和病理变化检测。经博来霉素处理的大鼠肺湿重和肺胶原蛋白含量均增加,体重下降(由于肺损伤和纤维化),但气管内给予S-TA可显著抑制这些变化。体外研究表明,S-TA以剂量依赖性方式(0.01-0.5mg/ml)抑制肺成纤维细胞增殖。在天然大鼠肺表面活性剂及其蛋白质和脂质成分中也观察到这种抑制作用。然而,S-TA并未改变培养的大鼠II型肺细胞数量,且可能保护II型细胞免于去分化。S-TA可能通过直接抑制肺成纤维细胞增殖来抑制博来霉素诱导的肺纤维化。