葡萄籽原花青素对博莱霉素诱导的大鼠实验性肺纤维化的治疗作用

发布时间：2017-12-27 01:30

本文关键词：葡萄籽原花青素对博莱霉素诱导的大鼠实验性肺纤维化的治疗作用　出处：《中国新药与临床杂志》2016年01期 　论文类型：期刊论文

【摘要】：目的探讨葡萄籽原花青素(GSP)对大鼠肺纤维化的治疗作用及其机制。方法 45只SD雄性大鼠随机分为正常对照组(N组)、模型组(M组)、GSP组(G组),每组15只。M、G组大鼠气管内一次性注入博莱霉素生理盐水溶液0.2~0.3 m L(5 mg·kg~(-1))造模,N组气管内注射等容生理盐水。术后第2日开始,G组大鼠给予GSP生理盐水溶液0.1 m L·10 g~(-1)(500 mg·kg~(-1)·d~(-1))灌胃,M组和N组给予等容生理盐水,每日1次。给药7、14、28 d每组随机处死5只大鼠,取肺组织。观察肺组织病理变化,检测肺组织匀浆羟脯氨酸(HYP)含量,RT-q PCR法和Western blot法检测血管内皮生长因子(VEGF)及其受体1(VEGFR1)m RNA和蛋白质的表达。结果各时间点M组Ashcroft评分均高于N组(P0.01)和G组(P0.05),N组大鼠肺组织无明显病变,M组肺组织炎症反应和肺纤维化明显,G组各期肺泡炎症和纤维化程度均低于M组。各观察时点,M组大鼠肺组织HYP含量、VEGF和VEGFR1蛋白及m RNA表达均明显高于N组(P0.01)。G组肺组织HYP含量、VEGF蛋白及m RNA表达均低于M组(P0.05或P0.01),给药7、14 d肺组织VEGFR1蛋白及m RNA表达低于M组(P0.05),给药28 d与M组比较差异无显著意义(P0.05)。结论 GSP能抑制大鼠肺纤维化,降低肺组织VEGF和VEGFR1蛋白和m RNA的表达可能为其作用机制之一。
[Abstract]:Objective to investigate the therapeutic effect and mechanism of grape seed proanthocyanidin (GSP) on pulmonary fibrosis in rats. Methods 45 SD male rats were randomly divided into normal control group (group N), model group (group M) and group GSP (group G), with 15 rats in each group. The rats in group M and G were injected with bryomycin saline solution 0.2~0.3 m L (5 mg kg~ (-1)), and the normal saline was injected into the trachea of the group of N. On the second day after operation, the rats in group G were given GSP normal saline solution 0.1 M L 10 g~ (-1) (500 mg kg~ (-1) / d~ (-1)) to intragastric administration, and the rats in the control group were given equal volume of normal saline 1 times a day. 5 rats were killed in each group at 7, 14, and 28 d, and the lung tissue was taken. The pathological changes of lung tissue were observed. The content of hydroxyproline (HYP) in lung homogenate was detected. The expression of vascular endothelial growth factor (VEGF) and its receptor 1 (VEGFR1) m RNA and protein were detected by RT-q PCR and Western blot. Results at each time point, the Ashcroft scores in group M were higher than those in group N (P0.01) and G group (P0.05). There was no obvious lesion in lung tissue of N group, and inflammatory reaction and pulmonary fibrosis in M group were significantly different. The degree of alveolar inflammation and fibrosis in G group was lower than that in M group. The HYP content of lung tissue, VEGF and VEGFR1 protein and m RNA expression in group M rats were significantly higher than those in group N (P0.01) at each observation point. The HYP content, VEGF protein and m RNA expression in lung tissue of group G were lower than those of M group (P0.05 or P0.01). The expression of VEGFR1 protein and m VEGFR1 in lung tissue was 7 and 14 d, respectively. The expression of VEGFR1 protein and m RNA in lung tissue were lower than those in group C. (28), there was no significant difference between them. Conclusion GSP can inhibit the pulmonary fibrosis in rats and reduce the expression of VEGF and VEGFR1 protein and m RNA in lung tissue, which may be one of the mechanisms of its action.
【作者单位】：重庆医科大学附属第一医院;
【基金】：重庆市应用开发计划项目(cstc2014yykf A110026) 国家临床重点专科专项(卫办医政函[2012]649号)
【分类号】：R563
【正文快照】： 特发性肺纤维化(IPF)是呼吸系统最严重疾病之一,它广泛累及肺间质、肺泡和(或)细支气管,由于各种刺激因子介导肺内炎症细胞渗出,继之出现成纤维细胞大量聚集和细胞外基质过量沉积,肺组织弹性减退,肺质地变硬容积缩小,病程一般呈进行性发展,最终引起呼吸功能衰竭而死亡[1,2]。

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