Salidroside suppressing LPS-induced myocardial injury by inhibiting ROS-mediated PI3K/Akt/mTOR pathway in vitro and in vivo.
Salidroside suppressing LPS-induced myocardial injury by inhibiting ROS-mediated PI3K/Akt/mTOR pathway in vitro and in vivo.
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DOI：
10.1111/jcmm.12871
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发表时间：
2017-12
影响因子：
5.3
通讯作者：
Ma C
中科院分区：
文献类型：
--
作者：
Chen L;Liu P;Feng X;Ma C
本研究旨在观察红景天苷（Salidroside，Sal）对内毒素血症（LPS）大鼠心肌损伤的影响。SD大鼠随机分为5组：对照组、LPS组（15 mg/kg）、LPS+地塞米松组（2 mg/kg）、LPS+不同剂量Sal组（20、40 mg/kg）。进行血流动力学测量和苏木精-伊红染色。处死大鼠后测定血清肌酸激酶（CK）、乳酸脱氢酶、抗氧化酶过氧化氢酶（CAT）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-px）、谷胱甘肽、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-1 β（IL-1β）的活性。Western blot检测iNOS、考克斯-2、NF-κB和PI 3 K/Akt/mTOR通路蛋白表达。在体外，我们评估了Sal对LPS诱导的大鼠胚胎心脏来源的肌源性细胞系H9 c2的保护作用。采用流式细胞仪检测H9 c2细胞内活性氧（ROS）的含量，并检测细胞上清液中抗氧化酶CAT、SOD、GSH-px、谷胱甘肽-S-转移酶、TNF-α、IL-6和IL-1β的活性。Western blot检测PI 3 K/Akt/mTOR信号通路。结果，Sal显著减弱了上述指标。Sal可能通过抑制体内iNOS、考克斯-2、NF-κB和PI 3 K/Akt/mTOR通路发挥对LPS致大鼠心脏的保护作用。此外，通过在LPS刺激的H9 C2细胞中使用ROS清除剂N-乙酰基-L-半胱氨酸，证明了Sal与ROS介导的PI 3 K/Akt/mTOR通路相关的药理学作用。我们的研究结果表明，Sal可能是一种潜在的治疗药物，用于治疗心血管疾病。
The purpose of the present study was to investigate the effect of salidroside (Sal) on myocardial injury in lipopolysaccharide (LPS)‐induced endotoxemic in vitro and in vivo. SD rats were randomly divided into five groups: control group, LPS group (15 mg/kg), LPS plus dexamethasone (2 mg/kg), LPS plus Sal groups with different Sal doses (20, 40 mg/kg). Hemodynamic measurement and haematoxylin and eosin staining were performed. Serum levels of creatine kinase (CK), lactate dehydrogenase, the activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH‐px), glutathione, tumour necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), and interleukin‐1β (IL‐1β) were measured after the rats were killed. iNOS, COX‐2, NF‐κB and PI3K/Akt/mTOR pathway proteins were detected by Western blot. In vitro, we evaluated the protective effect of Sal on rat embryonic heart‐derived myogenic cell line H9c2 induced by LPS. Reactive oxygen species (ROS) in H9c2 cells was measured by flow cytometry, and the activities of the antioxidant enzymes CAT, SOD, GSH‐px, glutathione‐S‐transferase, TNF‐α, IL‐6 and IL‐1β in cellular supernatant were measured. PI3K/Akt/mTOR signalling was examined by Western blot. As a result, Sal significantly attenuated the above indices. In addition, Sal exerts pronounced cardioprotective effect in rats subjected to LPS possibly through inhibiting the iNOS, COX‐2, NF‐κB and PI3K/Akt/mTOR pathway in vivo. Furthermore, the pharmacological effect of Sal associated with the ROS‐mediated PI3K/Akt/mTOR pathway was proved by the use of ROS scavenger, N‐acetyl‐l‐cysteine, in LPS‐stimulated H9C2 cells. Our results indicated that Sal could be a potential therapeutic agent for the treatment of cardiovascular disease.
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