1. College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou 730000, China.
2. Department of Pharmacy, the 940th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Key Laboratory of the Plateau Medicine, Lanzhou 730050, China.
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2022 Aug 1;51(4):422-429. doi: 10.3724/zdxbyxb-2022-0157.
To study the protective effect and mechanism of salidroside on lung tissue of rats exposed rapidly to high altitude.
Thirty-six Wistar male rats were randomly divided into blank control group, model control group, capsule (137 mg/kg) group, salidroside low-dose (14 mg/kg), medium-dose (28 mg/kg) and high-dose (56 mg/kg) groups, with 6 rats in each group. After 5 continuous days of drug administration in the plain lab, rats were rapidly moved to 4010 m plateau field lab. After exposure to hypoxia condition for 3 days the blood gas indexes were detected; the serum levels of inflammatory factors were measured by enzyme linked immunosorbent assay (ELISA); the oxidative stress index of lung tissue was measured; the pathological changes of lung tissue were observed by microscopy with hematoxylin and eosin (HE) staining; and the expression of occludin in lung tissues was determined by western blotting.
Compared with blank control group, arterial oxygen saturation (SaO ), arterial oxygen partial pressure (PaO ), blood pH, standard bicarbonate (SBC) and actual bicarbonate levels in model control group were significantly decreased, and hemoglobin level was significantly increased (all <0.05). In the model control group, the contents of mast cell protease (MCP) 1, interleukin (IL)-6 and IL-1β were significantly increased, while the contents of interferon-γ were significantly decreased (all <0.01). The contents of glutathione and total superoxide dismutase in the lung tissues of model control group were significantly decreased, while the content of malondialdehyde was significantly increased (all <0.01). After and salidroside were given, SaO , pH, hemoglobin, SBC and actual bicarbonate were improved compared with the model control group. Compared with the model control group, the group and salidroside groups had different degrees of improvement in the contents of the above inflammatory factors and oxidative stress indexes, and the salidroside groups had better improvement in MCP-1 and IL-6 than the group. HE staining showed that, after the administration of capsules and salidroside at low, medium and high doses, the hypoxic injury was significantly improved, the cell wall gradually became thinner, and the alveolar wall gradually became complete. The expression of occludin in the model control group was lower than that in the blank control group ( <0.05), while the expression of occludin in the salidroside high-dose group was significantly higher than that in the model control group ( <0.01).
Salidroside can improve the abnormality of blood gas index, hypoxia symptoms and acid-base balance disorder, dysregulation of inflammatory factors caused by hypoxia in rats, and improve lung tissue injury and oxidative stress injury, which has a protective effect on lung tissue injury of rats exposed rapidly to the high-altitude plateau, and the effect is better than capsule on the whole.
研究红景天苷对快速暴露于高原环境的大鼠肺组织的保护作用及机制。
将 36 只雄性 Wistar 大鼠随机分为空白对照组、模型对照组、胶囊(137mg/kg)组、红景天苷低剂量(14mg/kg)组、中剂量(28mg/kg)组和高剂量(56mg/kg)组,每组 6 只。在平原实验室连续给药 5 天后,大鼠迅速转移到 4010m 高原野外实验室。在缺氧条件下暴露 3 天后,检测血气指标;采用酶联免疫吸附试验(ELISA)法检测血清炎症因子水平;测定肺组织氧化应激指标;用苏木精-伊红(HE)染色法观察肺组织的病理变化;采用 Western blot 法测定肺组织中闭合蛋白的表达。
与空白对照组比较,模型对照组大鼠动脉血氧饱和度(SaO )、动脉血氧分压(PaO )、血 pH 值、标准碳酸氢盐(SBC)和实际碳酸氢盐水平均显著降低,血红蛋白水平显著升高(均<0.05)。模型对照组大鼠肥大细胞蛋白酶(MCP)1、白细胞介素(IL)-6 和 IL-1β含量显著升高,干扰素-γ含量显著降低(均<0.01)。模型对照组大鼠肺组织谷胱甘肽和总超氧化物歧化酶含量显著降低,丙二醛含量显著升高(均<0.01)。给予 和红景天苷后,SaO 、pH 值、血红蛋白、SBC 和实际碳酸氢盐与模型对照组比较均有不同程度的改善。与模型对照组比较, 组和红景天苷组上述炎症因子和氧化应激指标均有不同程度的改善,且红景天苷组 MCP-1 和 IL-6 改善程度优于 组。HE 染色显示,给予 胶囊和红景天苷低、中、高剂量后,缺氧损伤明显改善,细胞壁逐渐变薄,肺泡壁逐渐完整。模型对照组大鼠闭合蛋白表达水平低于空白对照组(<0.05),而红景天苷高剂量组大鼠闭合蛋白表达水平明显高于模型对照组(<0.01)。
红景天苷可改善大鼠因高原缺氧导致的血气指标异常、低氧症状和酸碱平衡紊乱,纠正缺氧所致炎症因子失调,改善肺组织损伤和氧化应激损伤,对大鼠快速暴露于高原环境所致肺组织损伤具有保护作用,整体效果优于 胶囊。