Xu Min, Cao Fa-le, Zhang Yu-fei, Shan Liang, Jiang Xiao-ling, An Xiao-jing, Xu Wei, Liu Xiu-zhi, Wang Xiao-yan
Department of Pathology, 88th Hospital of PLA, Taian 271000, China.
Department of Neurology, 88th Hospital of PLA, Taian 271000, China.
Acta Pharmacol Sin. 2015 Feb;36(2):179-87. doi: 10.1038/aps.2014.112. Epub 2014 Dec 29.
To study the effects of tanshinone IIA (TIIA) on lipopolysaccharide (LPS)-induced acute lung injury in mice and the underlying mechanisms.
Mice were injected with LPS (10 mg/kg, i.p.), then treated with TIIA (10 mg/kg, i.p.). Seven hours after LPS injection, the lungs were collected for histological study. Protein, LDH, TNF-α and IL-1β levels in bronchoalveolar lavage fluid (BALF) and myeloperoxidase (MPO) activity in lungs were measured. Cell apoptosis and Bcl-2, caspase-3, NF-κB and HIF-1α expression in lungs were assayed.
LPS caused marked histological changes in lungs, accompanied by significantly increased lung W/D ratio, protein content and LDH level in BALF, and Evans blue leakage. LPS markedly increased neutrophil infiltration in lungs and inflammatory cytokines in BALF. Furthermore, LPS induced cell apoptosis in lungs, as evidenced by increased TUNEL-positive cells, decreased Bcl-2 content and increased cleaved caspase-3 content. Moreover, LPS significantly increased the expression of NF-κB and HIF-1α in lungs. Treatment of LPS-injected mice with TIIA significantly alleviated these pathological changes in lungs.
TIIA alleviates LPS-induced acute lung injury in mice by suppressing inflammatory responses and apoptosis, which is mediated via inhibition of the NF-κB and HIF-1α pathways.
研究丹参酮IIA（TIIA）对脂多糖（LPS）诱导的小鼠急性肺损伤的影响及其潜在机制。
给小鼠腹腔注射LPS（10mg/kg），然后腹腔注射TIIA（10mg/kg）。LPS注射7小时后，收集肺组织进行组织学研究。检测支气管肺泡灌洗液（BALF）中的蛋白质、乳酸脱氢酶（LDH）、肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）水平以及肺组织中的髓过氧化物酶（MPO）活性。检测肺组织中的细胞凋亡以及Bcl-2、半胱天冬酶-3（caspase-3）、核因子-κB（NF-κB）和缺氧诱导因子-1α（HIF-1α）表达。
LPS导致肺组织出现明显的组织学变化，同时伴有肺组织湿/干重比、BALF中蛋白质含量和LDH水平显著升高以及伊文思蓝渗漏。LPS显著增加肺组织中的中性粒细胞浸润和BALF中的炎性细胞因子。此外，LPS诱导肺组织细胞凋亡，表现为TUNEL阳性细胞增加、Bcl-2含量降低和裂解的caspase-3含量增加。而且，LPS显著增加肺组织中NF-κB和HIF-1α的表达。用TIIA处理注射LPS的小鼠可显著减轻肺组织的这些病理变化。
TIIA通过抑制炎症反应和细胞凋亡减轻LPS诱导的小鼠急性肺损伤，其机制是通过抑制NF-κB和HIF-1α信号通路介导的。
