Saikosaponin-d regulates angiogenesis in idiopathic pulmonary fibrosis through angiopoietin/Tie-2 pathway

IF 2.3 4区 生物学 Q4 CELL BIOLOGY
Yan Wu , Jun Zhang , Xintian Wang , Yuncong Xu , Jinxu Zheng
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引用次数: 0

Abstract

Objective

Idiopathic pulmonary fibrosis (IPF) is considered as a chronic interstitial lung disease with underlying mechanism of IPF remaining unclear, while there are no definitive treatment options. In recent years, scientists have gradually paid attention to the influence of angiogenesis on IPF. Because IPF is a progressive with microvascular remodeling disorder, scientists have postulated that angiogenesis may also be one of the initiating and contributing factors of the disease. Bupleurum is a common natural Chinese herbal medicine with antibacterial, anti-inflammatory, anti-tumor and other pharmacological effects. As the most important active monomer of Bupleurum, Saikosaponin-d (SSd) is a new discovery with anti-pulmonary fibrosis (PF) activity. This study attempts to investigate the role of SSd in the interference of PF through regulation of angiogenesis in IPF through Angiopoietin (Angpt) /Tie receptor 2 (Tie2) pathway.

Methods

Randomly, we allocated C57BL/6 mice into four groups (n = 20 in each group). Afterwards, establishment of IPF model was accomplished via intratracheal administration of bleomycin (BLM, 5 mg/kg), while corresponding drug intervention was given accordingly. On 3rd, 7th, 14th and 28th days after modeling, we performed histopathological examination through staining. Meanwhile, immunohistochemistry (IHC) of PF and the expression of related factors were observed, while Ang/Tie2 pathway was assessed by ELISA with the effect of SSd on angiogenesis related proteins in IPF being explored with IHC and Western Blot technique.

Results

Our results showed that SSd could reduce inflammation and PF levels in lung tissue of experimental mice, while levels of angiogenesis-related factors, namely Tie-2, Ang-1 and ANGPT2 (Ang-2), fibrosis- associated factors like Alpha-smooth muscle actin (α-SMA), collagen-I and hydroxyproline in SSd and dexamethasone (DXM) mice were significantly reduced at each time point compared to BLM (p < 0.01). Additionally, we discovered substantial decreased expressions of Ang-1, Ang-2, Tie-2, α-SMA and collagen-I at protein level in SSd and DXM mice at each time point compared to BLM (p < 0.05). Besides, insignificant differences were observed between SSd and DXM groups (p > 0.05).

Conclusion

This study has demonstrated that SSd could down-regulate the expression of ANG-1, Ang-2 and Tie2 in the Ang/Tie2 pathway, and may reduce lung inflammation and PF in BLM-induced mice via inhibition of angiogenesis.

Saikosaponin-d通过血管生成素/Tie-2途径调节特发性肺纤维化的血管生成。
目的:特发性肺纤维化(IPF)被认为是一种慢性间质性肺病,其潜在机制尚不清楚,但尚无明确的治疗方案。近年来,科学家们逐渐关注血管生成对IPF的影响。由于IPF是一种进行性微血管重塑障碍,科学家们推测血管生成也可能是该疾病的起始和促成因素之一。柴胡是一种常见的天然中草药,具有抗菌、抗炎、抗肿瘤等药理作用。柴胡皂苷-d(SSd)作为柴胡最重要的活性单体,是一种具有抗肺纤维化(PF)活性的新发现。本研究试图通过血管生成素(Angpt)/Tie受体2(Tie2)途径调节IPF中的血管生成,探讨SSd在PF干扰中的作用。方法:将C57BL/6小鼠随机分为4组(每组20只)。然后,通过气管内给予博莱霉素(BLM,5mg/kg)建立IPF模型,并给予相应的药物干预。在建模后第3、7、14和28天,我们通过染色进行组织病理学检查。同时,观察PF的免疫组织化学(IHC)和相关因子的表达,同时用ELISA法评估Ang/Tie2通路,并用IHC和Western Blot技术探讨SSd对IPF血管生成相关蛋白的影响。结果:SSd可降低实验小鼠肺组织炎症和PF水平,而血管生成相关因子Tie-2、Ang-1和ANGPT2(Ang-2)、纤维化相关因子α-平滑肌肌动蛋白(α-SMA)、,与BLM相比,SSd和地塞米松(DXM)小鼠的胶原I和羟脯氨酸在每个时间点都显著降低(p0.05)。结论:本研究表明,SSd可以下调ANG/Tie2通路中ANG-1、ANG-2和Tie2的表达,并可能通过抑制血管生成来减轻BLM诱导的小鼠的肺部炎症和PF。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Acta histochemica
Acta histochemica 生物-细胞生物学
CiteScore
4.60
自引率
4.00%
发文量
107
审稿时长
23 days
期刊介绍: Acta histochemica, a journal of structural biochemistry of cells and tissues, publishes original research articles, short communications, reviews, letters to the editor, meeting reports and abstracts of meetings. The aim of the journal is to provide a forum for the cytochemical and histochemical research community in the life sciences, including cell biology, biotechnology, neurobiology, immunobiology, pathology, pharmacology, botany, zoology and environmental and toxicological research. The journal focuses on new developments in cytochemistry and histochemistry and their applications. Manuscripts reporting on studies of living cells and tissues are particularly welcome. Understanding the complexity of cells and tissues, i.e. their biocomplexity and biodiversity, is a major goal of the journal and reports on this topic are especially encouraged. Original research articles, short communications and reviews that report on new developments in cytochemistry and histochemistry are welcomed, especially when molecular biology is combined with the use of advanced microscopical techniques including image analysis and cytometry. Letters to the editor should comment or interpret previously published articles in the journal to trigger scientific discussions. Meeting reports are considered to be very important publications in the journal because they are excellent opportunities to present state-of-the-art overviews of fields in research where the developments are fast and hard to follow. Authors of meeting reports should consult the editors before writing a report. The editorial policy of the editors and the editorial board is rapid publication. Once a manuscript is received by one of the editors, an editorial decision about acceptance, revision or rejection will be taken within a month. It is the aim of the publishers to have a manuscript published within three months after the manuscript has been accepted
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