Bleomycin-induced diffuse interstitial pulmonary fibrosis in baboons.
Bleomycin-induced diffuse interstitial pulmonary fibrosis in baboons.
复制标题
博来霉素诱导狒狒弥漫性间质性肺纤维化。
DOI：
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发表时间：
2015
影响因子：
15.9
通讯作者：
W. Johanson
中科院分区：
文献类型：
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作者：
J. Collins;Bruce McCullough;J. Coalson;W. Johanson
用博莱霉素诱导八只狒狒发生肺纤维化；五只未经处理的动物作为对照。博来霉素45-65 U/kg后，肺容积和弥散能力减少，静态肺压力-容积曲线右移。此时，五只博莱霉素治疗动物和两只对照动物的右中叶被切除。与对照组相比，博莱霉素治疗动物的右中叶重量增加，总蛋白、胶原蛋白、弹性蛋白和 DNA 含量增加；胶原蛋白和非胶原蛋白的合成也有所增加。偶见肺泡间隔水肿并被单核炎症细胞浸润；组织学上可以证明胶原蛋白略有增加。在接受 95 U/kg 博莱霉素治疗后，六只接受治疗的动物中有四只死于广泛的弥漫性间质纤维化。生化分析显示，肺叶的干重、蛋白质、弹性蛋白和胶原蛋白含量显着升高。两只动物在 95 U/kg 博来霉素治疗后存活，并在治疗后 6 个月处死。在这些动物中，生理学研究表明存在限制性肺病，但肺组织学几乎正常。肺重量、总蛋白和 DNA 已恢复至对照值，但胶原蛋白和弹性蛋白的数量和浓度有所增加。博来霉素会引起肺部强烈的炎症反应。在炎症过程中，结缔组织增殖与其他组织成分的增殖同时发生。停止博莱霉素治疗后，炎症消退，表现为组织质量、细胞含量和非结缔组织蛋白减少。炎症期间沉积的胶原蛋白和弹性蛋白在消退过程中不太能被成功去除，导致进入以这些蛋白质浓度增加为特征的阶段。人类因各种肺损伤而发生的特发性弥漫性间质纤维化可能会发生类似的组织改变序列。
Pulmonary fibrosis was induced in eight baboons with bleomycin; five untreated animals were controls. After 45-65 U/kg of bleomycin, lung volumes and diffusing capacity were reduced, and static lung pressure-volume curves were shifted to the right. Right middle lobes were resected at this time in five bleomycin-treated and two control animals. Compared to controls, right middle lobes from bleomycintreated animals had increased weight and contained increased amounts of total protein, collagen, elastin, and DNA; synthesis of collagen and noncollagen protein were also elevated. Occasional alveolar septae were edematous and infiltrated by mononuclear inflammatory cells; a slight increase in collagen was demonstrable histologically. Four of six treated animals died with extensive diffuse interstitial fibrosis after 95 U/kg of bleomycin. Biochemical analyses revealed significantly elevated lobar contents of dry weight, protein, elastin, and collagen. Two animals survived 95 U/kg of bleomycin and were terminated 6 mo after treatment. In these animals, physiologic studies were indicative of restrictive lung disease, but lung histology was nearly normal. Lung weight, total protein, and DNA had returned to control values, but collagen and elastin were increased in amount and concentration. Bleomycin induces an intense inflammatory response in the lung. During this inflammation, connective tissue proliferation occurs in concert with proliferation of other tissue components. Cessation of bleomycin treatment is followed by resolution of inflammation manifested by decreases in tissue mass, cellular content, and nonconnective tissue protein. Collagen and elastin deposited during inflammation are less successfully removed during resolution, leading to a stage characterized by increased concentrations of these proteins. A similar sequence of tissue alterations may occur in idiopathic diffuse interstitial fibrosis of man in response to various lung injuries.