依那西普抑制博来霉素诱导的小鼠肺纤维化

发布时间：2018-04-02 10:28

本文选题：肺纤维化　切入点：肿瘤坏死因子α　出处：《中国病理生理杂志》2013年06期

【摘要】：目的:观察肿瘤坏死因子α(TNF-α)拮抗剂依那西普对博来霉素诱导的肺纤维化小鼠的抑制纤维化作用,并探讨依那西普治疗肺纤维化的可能机制。方法:将45只SPF级雌性昆明小鼠随机分为3组:对照组(气管内雾化生理盐水)、纤维化组(气管内博来霉素3 mg/kg溶于100μL生理盐水内雾化)和依那西普干预组(气管内雾化博来霉素后,4 mg/kg依那西普溶于100μL生理盐水内腹腔注射,每3 d注射1次)。处理后第28 d收集样本,小鼠左肺置于10%中性甲醛固定,石蜡包埋切片后行HE与Masson染色;右肺碱水解法检测组织羟脯氨酸(HYP)的含量;酶联免疫法检测血清TNF-α和转化生长因子β(TGF-β)的含量;提取肺组织总蛋白,Western blot-ting检测磷酸化ERK1/2、JNK和p38的表达。结果:依那西普干预组肺组织病理损伤及气道上皮下胶原沉积较纤维化组减轻,肺叶炎症损伤评分和纤维化评分明显下降(均P0.01),肺组织HYP含量显著降低(P0.05),血清TNF-α和TGF-β的浓度明显减少(均P0.01),肺组织ERK1/2、JNK和p38蛋白的磷酸化水平也显著下降(P0.01,P0.05,P0.01)。结论:依那西普能显著下调TNF-α和TGF-β的水平,从而抑制ERK1/2、JNK和p38的活化,缓解博来霉素诱导的小鼠肺纤维化病变。
[Abstract]:Aim: to observe the inhibitory effect of Enazepine, an antagonist of tumor necrosis factor 伪 (TNF- 伪), on pulmonary fibrosis induced by bleomycin in mice. Methods: 45 SPF grade female Kunming mice were randomly divided into three groups: control group (intratracheal nebulized normal saline), fibrosis group (intratracheal bleomycin 3 mg/kg soluble in the trachea). 100 渭 L normal saline atomization) and enazepine intervention group (4 mg/kg after intratracheal atomization of bleomycin) were injected intraperitoneally in 100 渭 L saline. The left lung of the mice was fixed with 10% neutral formaldehyde and stained with HE and Masson after paraffin-embedded sections, and the content of hydroxyproline was detected by hydrolysation of the right lung. The levels of TNF- 伪 and TGF- 尾 in serum were detected by enzyme-linked immunosorbent assay (Elisa). The expression of phosphorylated ERK1 / 2 JNK and p38 in lung tissue was detected by Western blot-ting. Results: compared with fibrotic group, the lung tissue pathological injury and airway subepithelial collagen deposition were alleviated in the treatment group. The pulmonary inflammatory injury score and fibrosis score were significantly decreased (all P 0.01, P 0.05), serum TNF- 伪 and TGF- 尾 were significantly decreased (all P 0.01), and the phosphorylation levels of ERK1 / 2, JNK and p38 protein were also significantly decreased in lung tissue (P 0.01 P 0.05 P 0.01). The levels of TNF- 伪 and TGF- 尾 were significantly down-regulated by Einacetin. Thus inhibiting the activation of ERK1 / 2 JNK and p38 and alleviating bleomycin induced pulmonary fibrosis in mice.
【作者单位】：广州军区广州总医院呼吸内科;南方医科大学研究生学院;
【基金】：广东省自然科学基金资助项目(No.S2011010000511) 广东省科技计划项目(No.2010B031600122)
【分类号】：R363

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