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丹参酮 IIA 通过调节大鼠血管紧张素转换酶 2/血管紧张素-(1-7)减轻百草枯诱导的急性肺损伤。

Tanshinone IIA attenuates paraquat‑induced acute lung injury by modulating angiotensin‑converting enzyme 2/angiotensin‑(1‑7) in rats.

机构信息

Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.

Department of Pediatrics of Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.

出版信息

Mol Med Rep. 2018 Sep;18(3):2955-2962. doi: 10.3892/mmr.2018.9281. Epub 2018 Jul 16.

Abstract

Tanshinone IIA (TIIA) is an active compound that can be isolated from the Chinese herb, Salvia miltiorrhizae Bunge, also known as danshen. Previous studies have demonstrated that TIIA can effectively attenuate bleomycin‑induced pulmonary fibrosis in rats. However, it has not been determined whether TIIA can attenuate paraquat (PQ)‑induced acute lung injury (ALI). In the present study, the protective effects exhibited by TIIA on PQ‑induced ALI, as well as its underlying mechanisms, were investigated using Sprague‑Dawley (SD) rats. ALI animal models using rats were established via administration of PQ. Adult male SD rats were randomly divided into three groups: A control group, a PQ group and a PQ + TIIA group. Total cell count, total protein levels and lactic dehydrogenase (LDH) levels in bronchoalveolar lavage fluid (BALF), as well as myeloperoxidase (MPO) activity in lung tissues were determined. Lung histological alterations were also investigated. Angiotensin converting enzyme 2 (ACE2) and Angiotensin 1‑7 [Ang‑(1‑7)] expression levels in the lung were also analyzed. The results demonstrated that administration of PQ induced marked histological alterations, and markedly increased neutrophil infiltration, lung wet/dry weight ratio, total cell count, protein content and LDH levels in BALF. In addition, PQ was revealed to significantly decrease ACE2 and Ang‑(1‑7) expression levels in lung tissues. However, it was demonstrated that TIIA attenuated these effects. Therefore, the results of the present study suggest that that TIIA may exhibit a therapeutic effect regarding PQ‑induced ALI in rats, and that ACE2 and Ang‑(1‑7) may be involved in the underlying mechanisms of this effect.

摘要

丹参酮 IIA(TIIA)是一种可从中药丹参(Salvia miltiorrhizae Bunge)中分离出来的活性化合物。先前的研究表明,TIIA 可有效减轻博来霉素诱导的大鼠肺纤维化。然而,目前尚不清楚 TIIA 是否可减轻百草枯(PQ)诱导的急性肺损伤(ALI)。在本研究中,采用 SD 大鼠研究了 TIIA 对 PQ 诱导的 ALI 的保护作用及其潜在机制。通过给予 PQ 建立 ALI 动物模型。将成年雄性 SD 大鼠随机分为三组:对照组、PQ 组和 PQ+TIIA 组。测定支气管肺泡灌洗液(BALF)中的总细胞计数、总蛋白水平和乳酸脱氢酶(LDH)水平,以及肺组织中的髓过氧化物酶(MPO)活性。还研究了肺组织学改变。分析了肺中的血管紧张素转换酶 2(ACE2)和血管紧张素 1-7 [Ang-(1-7)]表达水平。结果表明,给予 PQ 可引起明显的组织学改变,并显著增加中性粒细胞浸润、肺湿/干重比、BALF 中的总细胞计数、蛋白含量和 LDH 水平。此外,PQ 显著降低了肺组织中的 ACE2 和 Ang-(1-7)表达水平。然而,TIIA 可减轻这些作用。因此,本研究的结果表明,TIIA 可能对大鼠 PQ 诱导的 ALI 具有治疗作用,ACE2 和 Ang-(1-7)可能参与了这种作用的潜在机制。

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