Breviscapine ameliorates CCl4‑induced liver injury in mice through inhibiting inflammatory apoptotic response and ROS generation.
Breviscapine ameliorates CCl4‑induced liver injury in mice through inhibiting inflammatory apoptotic response and ROS generation.
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DOI：
10.3892/ijmm.2018.3651
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发表时间：
2018-08
影响因子：
5.4
通讯作者：
He Q
中科院分区：
文献类型：
--
作者：
Liu Y;Wen PH;Zhang XX;Dai Y;He Q
急性肝损伤以肝纤维化、炎症和细胞凋亡为特征，可导致肝功能衰竭、肝硬变或癌症，长期影响临床转归。然而，目前还没有有效的治疗策略可用。灯盏花素是一种黄酮苷的混合物，已有报道具有多种生物学功能。本研究旨在探讨灯盏花素对CCl4所致小鼠急性肝损伤的影响。C57BL/6小鼠经腹腔注射CCl4 8周后，分别给予或不给予灯盏花素(15 mg/kg或30 mg/kg)。经CCl4处理的小鼠出现急性肝损伤，组织学分析、Masson三色染色和天狼星红染色证实，并伴有丙氨酸转氨酶和天冬氨酸转氨酶水平升高。此外，还观察到促炎症细胞因子、趋化因子和凋亡因子的增加，包括caspase-3和多聚ADP核糖聚合酶-2(PARP-2)。灯盏花素治疗显著减少胶原沉积和纤维化面积，并呈剂量依赖关系。灯盏花素通过失活Toll样受体4/核因子-κB信号通路下调炎性细胞因子的表达。此外，灯盏花素与CCl_4合用可通过提高B细胞淋巴瘤-2(Bc l-2)的水平，降低Bc l-2相关的X蛋白、凋亡酶激活因子1、caspase-3和PARP的活性，从而降低细胞的凋亡反应。此外，灯盏花素通过改善抗氧化剂和阻止丝裂原激活的蛋白激酶通路来阻断CCl4诱导的氧化应激。本研究强调灯盏花素通过抑制炎症和细胞凋亡而对CCl4诱导的急性肝损伤具有肝保护作用。
Acute liver injury is characterized by fibrosis, inflammation and apoptosis, leading to liver failure, cirrhosis or cancer and affecting the clinical outcome in the long term. However, no effective therapeutic strategy is currently available. Breviscapine, a mixture of flavonoid glycosides, has been reported to have multiple biological functions. The present study aimed to investigate the effects of breviscapine on acute liver injury induced by CCl4 in mice. C57BL/6 mice were subjected to intraperitoneal injection with CCl4 for 8 weeks with or without breviscapine (15 or 30 mg/kg). Mice treated with CCl4 developed acute liver injury, as evidenced by histological analysis, Masson trichrome and Sirius Red staining, accompanied with elevated levels of alanine aminotransferase and aspartate aminotransferase. Furthermore, increases in pro-inflammatory cytokines, chemokines and apoptotic factors, including caspase-3 and poly(ADP ribose) polymerase-2 (PARP-2), were observed. Breviscapine treatment significantly and dose-dependently reduced collagen deposition and the fibrotic area. Inflammatory cytokines were downregulated by breviscapine through inactivating Toll-like receptor 4/nuclear factor-κB signaling pathways. In addition, co-administration of breviscapine with CCl4 decreased the apoptotic response by enhancing B-cell lymphoma-2 (Bcl-2) levels, while reducing Bcl-2-associated X protein, apoptotic protease activating factor 1, caspase-3 and PARP activity. Furthermore, CCl4-induced oxidative stress was blocked by breviscapine through improving anti-oxidants and impeding mitogen-activated protein kinase pathways. The present study highlighted that breviscapine exhibited liver-protective effects against acute hepatic injury induced by CCl4 via suppressing inflammation and apoptosis.
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DOI：
10.1111/1440-1681.12230
发表时间：
2014-06-01
影响因子：
2.9
作者：
Esmaeili, Mohammad Ali;Alilou, Mostafa
通讯作者：
Alilou, Mostafa
影响因子：
8
作者：
Fujioka, S;Sclabas, GM;Chiao, PJ
通讯作者：
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影响因子：
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作者：
Brentnall M;Rodriguez-Menocal L;De Guevara RL;Cepero E;Boise LH
通讯作者：
Boise LH
影响因子：
2.2
作者：
Lee, Jun Sik;Jung, Won-Kyo;Kim, Hyung Keun
通讯作者：
Kim, Hyung Keun
影响因子：
4.3
作者：
Huang, Hai-Li;Wang, Ya-Jing;Zhu, Run-Zhi
通讯作者：
Zhu, Run-Zhi