Antifibrotic therapy by sustained release of low molecular weight heparin from poly(lactic-co-glycolic acid) microparticles on bleomycin-induced pulmonary fibrosis in mice.
Antifibrotic therapy by sustained release of low molecular weight heparin from poly(lactic-co-glycolic acid) microparticles on bleomycin-induced pulmonary fibrosis in mice.
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聚乳酸-羟基乙酸共聚物微粒缓释低分子量肝素对博莱霉素诱导的小鼠肺纤维化的抗纤维化治疗。
DOI：
10.1038/s41598-020-76034-0
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发表时间：
2020-11-04
影响因子：
4.6
通讯作者：
Suzuki K
中科院分区：
文献类型：
--
作者：
Saito T;Kotani T;Suzuki K
肝素和低分子量肝素（LMWH）最近被认为是用于炎症的有用治疗工具。肝素具有抗纤维化活性，由肝细胞生长因子（HGF）的细胞分泌介导。肝细胞生长因子具有抗纤维化特性，在肺、肾、心脏、皮肤和肝纤维化的实验模型中得到证实。LMWH分泌HGF的能力与正常肝素相似。聚乳酸-羟基乙酸共聚物（PLGA）因其生物相容性和低毒性而被广泛用于药物缓释。负载LMWH的PLGA微粒通过常规的水包油包水乳液方法制备。间质性肺炎是一种危及生命的病理状况，当其进展时会导致呼吸衰竭。在本研究中，我们研究了负载LMWH的PLGA微粒在博莱霉素诱导的肺纤维化小鼠模型中的治疗效果。在施用负载LMWH的微粒的小鼠中纤维化面积与总面积的比率显著低于单独施用博来霉素的小鼠。微粒给药没有进一步增强炎性细胞因子的基因表达。在细胞培养研究中，通过添加LMWH，小鼠和人肺成纤维细胞的HGF分泌显著增加。我们得出结论，LMWH显示抗炎活性，通过LMWH负载的PLGA微粒对炎症部位细胞的影响。
Heparin and low molecular weight heparin (LMWH) have recently been considered useful treatment tools for inflammation. Heparin has antifibrotic activity, mediated by cellular secretion of hepatocyte growth factor (HGF). HGF has antifibrotic properties demonstrated in experimental models of lung, kidney, heart, skin, and liver fibrosis. The ability of LMWH for HGF secretion is similar to that of normal heparin. Poly (lactic-co-glycolic acid) (PLGA) is widely used for sustained drug release, because of its biocompatibility and low toxicity. LMWH-loaded PLGA microparticles are prepared by a conventional water-in-oil-in-water emulsion method. Interstitial pneumonia is a life-threatening pathological condition that causes respiratory failure when it progresses. In the present study, we investigated the therapeutic effect of LMWH-loaded PLGA microparticles in a mouse model of bleomycin-induced lung fibrosis. The ratios of fibrotic area to total area were significantly lower in mice administered LMWH-loaded microparticles than in mice administered bleomycin alone. The microparticle administration did not further enhance the gene expression for inflammatory cytokines. In a cell culture study, HGF secretion by mouse and human lung fibroblasts was significantly increased by LMWH addition. We conclude that LMWH showed anti-inflammatory activity, through the effects of LMWH-loaded PLGA microparticles on cells at sites of inflammation.
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影响因子：
5
作者：
Makadia HK;Siegel SJ
通讯作者：
Siegel SJ
影响因子：
6.1
作者：
Pecly, IMD;Gonçalves, RG;Leite, M
通讯作者：
Leite, M
影响因子：
19.6
作者：
Ma, Hong;Saenko, Maryanna;Ishibe, Shuta
通讯作者：
Ishibe, Shuta
DOI：
10.1124/jpet.111.190447
发表时间：
2012-05-01
影响因子：
3.5
作者：
Okamoto, Tatsuya;Uemoto, Shinji;Tabata, Yasuhiko
通讯作者：
Tabata, Yasuhiko
影响因子：
6
作者：
Hattori, N;Mizuno, S;Miyake, M
通讯作者：
Miyake, M