胰高血糖素样肽-1对博莱霉素诱导的小鼠肺纤维化的作用及机制探讨

发布时间：2018-03-26 01:44

本文选题：胰高血糖素样肽-　切入点：肺纤维化　出处：《四川大学学报(医学版)》2017年04期

【摘要】：目的探究在博莱霉素(BLM)诱导的小鼠肺纤维化疾病上,胰高血糖素样肽-1(GLP-1)的治疗价值和可能机制。方法采用气管内一次性灌注BLM(3 mg/kg)的方法建立小鼠肺部纤维化模型,同时腹腔注射GLP-1类似物利拉鲁肽(2mg/kg),每天1次,连续给药28d。在注入BLM 28d后,测定肺泡灌洗液中的细胞总数、巨噬细胞、中性粒细胞和淋巴细胞的数量以及转化生长因子-β1(TGF-β1)的质量浓度;取肺组织进行HE染色和Masson染色;采用Ashcroft评分标准评定纤维化程度等级,测定羟脯氨酸(HYP)的含量;实时荧光定量PCR和免疫印迹法测定α平滑肌肌动蛋白(α-SMA)和血管细胞黏附分子-1(VCAM-1)的表达;免疫印迹法评估核因子(NF)-κB p65的磷酸化,通过核转录因子酶联免疫试剂盒测定NF-κB p65与DNA的结合。结果 GLP-1降低了BLM小鼠肺组织炎症细胞的浸润和肺泡灌洗液中TGF-β1的含量,Ashcroft评分等级和HYP含量亦降低,同时,BLM导致的α-SMA和VCAM-1的过表达也被阻止,磷酸化NF-κB p65/总NF-κB p65比值减小,NF-κB p65的DNA结合活性减弱。结论 GLP-1可能通过抑制NF-κB激活,减轻BLM诱导的小鼠肺部炎症和纤维化。
[Abstract]:Objective to explore the therapeutic value and possible mechanism of glucagon like peptide 1 (GLP-1) on bleomycin induced pulmonary fibrosis in mice. Methods Pulmonary fibrosis model was established by intratracheal instillation of BLM(3 mg / kg in mice. At the same time, the GLP-1 analogue was injected intraperitoneally with a dose of 2 mg / kg of GLP-1 analogue, once a day for 28 days. The total number of cells and macrophages in the alveolar lavage fluid were measured after BLM injection for 28 days. The number of neutrophils and lymphocytes and the mass concentration of TGF- 尾 _ 1 of TGF- 尾 _ 1 were collected from lung tissue for HE staining and Masson staining. The fibrotic grade was assessed by Ashcroft score, and the content of hydroxyproline (HYP) was measured. The expression of 伪 -smooth muscle actin (伪 -SMA-1) and vascular cell adhesion molecule-1 (VCAM-1) was detected by real-time fluorescence quantitative PCR and Western blotting, and the phosphorylation of NF-魏 B p65 was evaluated by Western blotting. The binding of NF- 魏 B p65 to DNA was determined by nuclear transcription factor enzyme linked immunosorbent kit. Results GLP-1 decreased the infiltration of inflammatory cells in lung tissue and the content of TGF- 尾 1 in alveolar lavage fluid of BLM mice. At the same time, the overexpression of 伪 -SMA and VCAM-1 induced by BLM was also blocked, and the ratio of phosphorylated NF- 魏 B p65 / total NF- 魏 B p65 decreased the DNA binding activity of NF- 魏 B p65. Conclusion GLP-1 may reduce the pulmonary inflammation and fibrosis induced by BLM by inhibiting the activation of NF- 魏 B.
【作者单位】：四川大学华西药学院药理教研室;
【分类号】：R563

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