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进一步探讨脂质体槲皮素的抗纤维化作用与肺纤维化中炎症细胞因子的相关性。

A further investigation concerning correlation between anti-fibrotic effect of liposomal quercetin and inflammatory cytokines in pulmonary fibrosis.

机构信息

State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.

出版信息

Eur J Pharmacol. 2010 Sep 10;642(1-3):134-9. doi: 10.1016/j.ejphar.2010.05.019. Epub 2010 May 26.

DOI:10.1016/j.ejphar.2010.05.019
PMID:20510684
Abstract

It is widely accepted that inflammatory cells and cytokines play vital roles in the process of pulmonary fibrosis. The aim of this study was to evaluate the preventative effects of liposomal quercetin against bleomycin-induced pulmonary fibrosis in vivo. The underlying molecular mechanisms were also investigated. Bleomycin was injected intratracheally at a single dose of 5 U/kg for pulmonary fibrosis induction. Liposomal quercetin was intravenously injected 1 day prior to bleomycin administration and continued to the end of the study (for 4 weeks). Our results showed that liposomal quercetin diminished the increase of total cell counts and macrophage counts in bronchoalveolar lavage fluid. The neutrophil and lymphocyte counts were also significantly decreased both on day 7 and 14 after liposomal quercetin injection (P<0.05). The levels of TNF-alpha, IL-1beta, and IL-6 in bronchoalveolar lavage fluid at day 7 were strikingly reduced in liposomal quercetin treated group compared with bleomycin-induced group (TNF-alpha: 56.21+/-3.16 pg/ml vs.79.85+/-6.91 pg/ml; IL-1beta: 37.64+/-2.10 pg/ml vs. 73.29+/-5.78 pg/ml; IL-6: 88.52+/-5.96 pg/ml vs. 128.56+/-8.72 pg/ml; P<0.05). Moreover, the treatment with liposomal quercetin exerted approximately 35.8% reduction of the hydroxyproline content in contrast to the bleomycin-induced group (P<0.05). Histopathological assessment revealed that treatment with liposomal quercetin apparently lessened the lung fibrosis areas and collagen deposition accompanied with decreased expression of TGF-beta1. Thus, our results suggested that liposomal quercetin could attenuate the bleomycin-induced pulmonary fibrosis in vivo by the suppression of inflammatory cytokines.

摘要

人们普遍认为,炎症细胞和细胞因子在肺纤维化过程中起着至关重要的作用。本研究旨在评估脂质体槲皮素对博莱霉素诱导的肺纤维化的预防作用,并探讨其潜在的分子机制。博莱霉素以 5U/kg 的单剂量气管内注射诱导肺纤维化。脂质体槲皮素在博莱霉素给药前 1 天静脉注射,并持续至研究结束(4 周)。我们的结果表明,脂质体槲皮素可减少支气管肺泡灌洗液中总细胞计数和巨噬细胞计数的增加。中性粒细胞和淋巴细胞计数在脂质体槲皮素注射后第 7 天和第 14 天也显著降低(P<0.05)。与博莱霉素诱导组相比,脂质体槲皮素治疗组第 7 天支气管肺泡灌洗液中 TNF-α、IL-1β和 IL-6 的水平显著降低(TNF-α:56.21±3.16pg/ml 比 79.85±6.91pg/ml;IL-1β:37.64±2.10pg/ml 比 73.29±5.78pg/ml;IL-6:88.52±5.96pg/ml 比 128.56±8.72pg/ml;P<0.05)。此外,与博莱霉素诱导组相比,脂质体槲皮素的羟脯氨酸含量降低了约 35.8%(P<0.05)。组织病理学评估表明,脂质体槲皮素治疗明显减轻了肺纤维化面积和胶原沉积,同时降低了 TGF-β1 的表达。因此,我们的结果表明,脂质体槲皮素可能通过抑制炎症细胞因子来减轻体内博莱霉素诱导的肺纤维化。

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