Abstract

Context

Salidroside, a compound extracted from Rhodiola rosea L. (Crassulaceae), possesses many beneficial pathological effects.

Objective

To explore the effect of salidroside on ventilator-induced lung endothelial dysfunction in vivo and in vitro.

Materials and methods

In vivo, male ICR mice were divided into sham, ventilation, salidroside, and ventilation plus salidroside groups. The mice were ventilated for 4 h, salidroside (50 mg/kg) was administrated intraperitoneally before ventilation, dexamethasone (Dex) (5 mg/kg) was used as a positive control. In vitro, mouse lung vascular endothelial cells (MLVECs) were treated with salidroside, MMP-9 siRNA, and BAY11-7082 (10 μM), and then exposed to cyclic stretch for 4 h. Afterward, lung tissues and MLVECs were collected for further analysis.

Results

Salidroside pre-treatment significantly reversed the expression of vascular endothelial cadherin (VE-cadherin) and zonula occluden-1 (ZO-1) proteins in cyclic stretch-treated MLVECs (0.46 ± 0.09 vs. 0.80 ± 0.14, 0.49 ± 0.05 vs. 0.88 ± 0.08) and ventilated lung tissues (0.56 ± 0.06 vs. 0.83 ± 0.46, 0.49 ± 0.08 vs. 0.80 ± 0.12). The results further indicated that salidroside inhibited the expression of matrix metalloproteinase-9 (MMP-9), whereas knockdown of its expression restored the expression levels of VE-cadherin (0.37 ± 0.08 vs. 0.85 ± 0.74) and ZO-1 (0.48 ± 0.08 vs. 0.81 ± 0.11) in stretched MLVECs. Meanwhile, salidroside inhibited the NF-κB signalling pathway and alleviated lung injury.

Conclusions

Salidroside protected against stretch-induced endothelial barrier function, improving lung injury after ventilation. Thus, salidroside may be a promising therapeutic agent for patients with MV-induced lung injury.

中文翻译：

---

红景天苷通过抑制基质金属蛋白酶9的表达来预防通气性肺损伤

摘要

语境

红景天苷是一种从红景天（景天科）中提取的化合物，具有许多有益的病理作用。

客观的

探讨红景天苷在体内外对呼吸机所致肺内皮功能障碍的影响。

材料和方法

在体内，将雄性ICR小鼠分为假手术组、通气组、红景天苷组和通气加红景天苷组。小鼠通气4 h，通气前腹腔给予红景天苷（50 mg/kg），地塞米松（Dex）（5 mg/kg）作为阳性对照。在体外，用红景天苷、MMP-9 siRNA 和 BAY11-7082 (10 μM) 处理小鼠肺血管内皮细胞 (MLVEC)，然后循环拉伸 4 小时。之后，收集肺组织和 MLVECs 用于进一步分析。

结果

红景天苷预处理显着逆转了循环拉伸处理的 MLVECs 中血管内皮钙粘蛋白 (VE-cadherin) 和 zonula occluden-1 (ZO-1) 蛋白的表达 (0.46 ± 0.09 vs. 0.80 ± 0.14, 0.49 ± 0.05 vs. 0.88 ± 0.08) 和通气肺组织 (0.56 ± 0.06 vs. 0.83 ± 0.46, 0.49 ± 0.08 vs. 0.80 ± 0.12)。结果进一步表明，红景天苷抑制基质金属蛋白酶-9 (MMP-9) 的表达，而抑制其表达则恢复了 VE-cadherin (0.37 ± 0.08 vs. 0.85 ± 0.74) 和 ZO-1 (0.48 ± 0.08对比0.81 ± 0.11) 在拉伸的 MLVEC 中。同时，红景天苷抑制NF-κB信号通路，减轻肺损伤。

结论

红景天苷可防止拉伸引起的内皮屏障功能，改善通气后的肺损伤。因此，红景天苷可能是用于 MV 引起的肺损伤患者的有前途的治疗剂。