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首页> 外文期刊>Cytokine >Protective effects of finasteride on the pulmonary immune response in a combined model of trauma-hemorrhage and polymicrobial sepsis in mice.
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Protective effects of finasteride on the pulmonary immune response in a combined model of trauma-hemorrhage and polymicrobial sepsis in mice.

机译：非那雄胺在小鼠创伤性出血和微生物败血症的组合模型中对肺部免疫反应的保护作用。

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摘要

Literature supports findings about a gender specific outcome following multiple trauma. Male sex hormones such as dihydrotestosterone (DHT) exert deleterious effects on the posttraumatic immune response whereas increased estradiol concentrations are correlated with improved outcome. Pretreatment with the 5alpha-reductase inhibitor finasteride resulted in an improved outcome following trauma-hemorrhage (TH) in mice. The present study tested the hypothesis that finasteride exerts beneficial effects on the posttraumatic immune response also in a combined setting of TH and sepsis when administered during the resuscitation process. MATERIAL AND METHODS: Male C57BL/6N-mice were subjected to TH (blood pressure, 35 mm Hg, 60 min) followed by finasteride application and fluid resuscitation. Thereafter, finasteride was administered every 12h. 24h after TH, sepsis was induced by cecal ligation and puncture (CLP) or sham operation was performed. Plasma cytokines (MIP-1alpha, MIP-1beta, TNF-alpha, MCP-1, IL-6), productive capacity by alveolar macrophages (AM) and systemic estradiol levels were determined 4 h thereafter. The expression of pro-inflammatory mediators in lung tissue was evaluated by PCR. Pulmonary infiltration of PMN was determined by immunohistochemical staining. RESULTS: Finasteride treatment resulted in a reduced posttraumatic cytokine secretion of AM as well as in a decreased concentration of MCP-1 and MIP-1beta in lung tissue. Systemic estradiol levels were increased following finasteride treatment. CONCLUSION: Finasteride mediates salutary effects on the pulmonary immune response using a therapeutical approach following TH-CLP in mice. Thus, finasteride might represent a relevant therapeutic substance following major trauma also in the clinical setting.
机译：文献支持有关多发性创伤后性别特定结局的发现。诸如二氢睾丸激素（DHT）之类的男性性激素对创伤后免疫反应产生有害影响，而雌二醇浓度升高与预后改善相关。用5alpha-还原酶抑制剂非那雄胺进行的预处理导致小鼠创伤性出血（TH）后的转归改善。本研究检验了以下假说：在复苏过程中使用非那雄胺在TH和脓毒症的组合环境中也对创伤后免疫应答产生有益作用。材料与方法：对雄性C57BL / 6N小鼠进行TH（血压，35 mm Hg，60分钟），然后应用非那雄胺并进行液体复苏。此后，非那雄胺每12小时给药一次。 TH后24h，盲肠结扎并穿刺（CLP）或进行假手术引起败血症。此后4小时测定血浆细胞因子（MIP-1α，MIP-1β，TNF-α，MCP-1，IL-6），肺泡巨噬细胞（AM）的生产能力和全身性雌二醇水平。通过PCR评估肺组织中促炎性介质的表达。通过免疫组织化学染色确定PMN的肺浸润。结果：非那雄胺治疗导致创伤后AM的细胞因子分泌减少，以及肺组织中MCP-1和MIP-1beta的浓度降低。非那雄胺治疗后全身性雌二醇水平升高。结论：非那雄胺在TH-CLP后可通过治疗方法介导对肺免疫反应的有益作用。因此，非那雄胺在临床上也可能代表重大创伤后的相关治疗物质。

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