Male sex hormones exacerbate lung function impairment after bleomycin-induced pulmonary fibrosis.
Male sex hormones exacerbate lung function impairment after bleomycin-induced pulmonary fibrosis.
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DOI：
10.1165/rcmb.2007-0340oc
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发表时间：
2008-02
影响因子：
6.4
通讯作者：
James W. Voltz;J. Card;Michelle A. Carey;L. Degraff;Catherine D. Ferguson;G. Flake;J. Bonner;K. Korach;D. Zeldin
中科院分区：
文献类型：
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作者：
James W. Voltz;J. Card;Michelle A. Carey;L. Degraff;Catherine D. Ferguson;G. Flake;J. Bonner;K. Korach;D. Zeldin
性激素作为肺功能和疾病的调节剂的作用已受到极大的关注，因为最近有报道称，对各种肺部侮辱的不同性别反应。本研究使用博莱霉素诱导的C57BL/6小鼠肺纤维化模型来检测生理和病理结果中潜在的性别差异。测量的终点包括侵入性肺功能评估、免疫学反应、肺胶原沉积和肺纤维化的定量组织学分析。雄性小鼠基础静态肺顺应性显著高于雌性小鼠(P<；0.05)，博莱霉素治疗后静态顺应性下降更明显，表现为总体变化或基线变化百分比(P<；0.05)。而博莱霉素治疗后肺组织免疫细胞渗入和肺总胶原含量在性别间差异无统计学意义。使用Ashcroft方法测量的总肺组织病理学评分在性别之间没有差异，而旨在确定肺内纤维化发生位置的定量组织病理学评分系统显示，在接受博莱霉素治疗的雄性小鼠与雌性小鼠相比，在紧邻呼吸道的情况下，有更多纤维化的倾向。此外，去势的雄性小鼠对博莱霉素表现出类似雌性的反应，而给予外源性雄激素的雌性小鼠表现出类似雄性的反应。这些数据表明，雄激素在博莱霉素治疗后肺功能下降中起加重作用，而传统的纤维化测量方法可能会忽略性别之间肺功能的关键差异。在设计和解释小鼠肺纤维化的实验模型时，应仔细考虑性别差异。
The roles of sex hormones as modulators of lung function and disease have received significant attention as differential sex responses to various lung insults have been recently reported. The present study used a bleomycin-induced pulmonary fibrosis model in C57BL/6 mice to examine potential sex differences in physiological and pathological outcomes. Endpoints measured included invasive lung function assessment, immunological response, lung collagen deposition, and a quantitative histological analysis of pulmonary fibrosis. Male mice had significantly higher basal static lung compliance than female mice (P < 0.05) and a more pronounced decline in static compliance after bleomycin administration when expressed as overall change or percentage of baseline change (P < 0.05). In contrast, there were no significant differences between the sexes in immune cell infiltration into the lung or in total lung collagen content after bleomycin. Total lung histopathology scores measured using the Ashcroft method did not differ between the sexes, while a quantitative histopathology scoring system designed to determine where within the lung the fibrosis occurred indicated a tendency toward more fibrosis immediately adjacent to airways in bleomycin-treated male versus female mice. Furthermore, castrated male mice exhibited a female-like response to bleomycin while female mice given exogenous androgen exhibited a male-like response. These data indicate that androgens play an exacerbating role in decreased lung function after bleomycin administration, and traditional measures of fibrosis may miss critical differences in lung function between the sexes. Sex differences should be carefully considered when designing and interpreting experimental models of pulmonary fibrosis in mice.