人参茎叶总皂苷对肾上腺素致家兔 肺水肿的保护机制研究

Protective effect of ginsenosides on pulmonary edema induced by adrenaline in rabbits

摘要:

目的 探讨人参茎叶总皂苷对家兔肾上腺素（AD）实验性肺水肿的作用。方法 随机将18 只 家兔分成对照组、模型组和治疗组。对照组等体积生理盐水灌胃；模型组等体积生理盐水灌胃，30 min 后耳 缘静脉注射AD（1 mg/ 只），复制AD 肺水肿模型，观察30 min ；治疗组以50 mg/kg 灌胃人参茎叶总皂苷， 连续7 d，末次给药30 min 后耳缘静脉注射AD（l mg/ 只）。记录不同时间点呼吸频率的变化，比较肺体系数、 超氧化物歧化酶（SOD）及丙二醛（MDA）含量，并行肺组织病理学分析，采用免疫组织化学法检测C/ EBPα 表达，采用流式细胞术与Western blotting 检测mTOR、S6K1、SirT1、NLRP3 蛋白的表达。结果 模 型组肺体系数、MDA 较对照组升高（P <0.05），SOD 较对照组低（P <0.05），治疗组肺体系数、MDA 较模 型组降低（P <0.05），SOD 较模型组升高（P <0.05）。病理学检查显示，模型组动物肺泡壁断裂，肺泡隔明显 增宽，有尘细胞。模型组肺组织损伤评分较对照组升高（P <0.05），治疗组较模型组降低（P <0.05）。模型组 mTOR 和S6K1 蛋白表达率较对照组升高（P <0.05），治疗组较模型组降低（P <0.05）。模型组NLRP3 较对 照组升高（P <0.05），SirT1 较对照组降低（P <0.05），治疗组NLRP3 较模型组降低（P <0.05），SirT1 较模型 组升高（P <0.05）。结论 人参茎叶总皂苷对AD 所致肺水肿具有保护作用，可能与降低C/EBPα、mTOR/ S6K1 及SirT1/NLRP3 表达有关。

Abstract:

Objective To investigate the effect of ginsenosides on the experimental pulmonary edema in rabbits. Methods A total of 18 rabbits were randomly divided into normal group, model group, ginsenosides group. In the ginsenosides group, rabbits received an intragastric administration of 50 mg/kg ginsenosides for 7 days, followed by injection of 1 mg adrenaline (AD) after 30 min. In the model group, 30 min after a corresponding bolus of normal saline, AD was administrated. Normal group were injected with a corresponding bolus of normal saline.The effect of ginsenosides was evaluated by light microscope, the indications of the animals as breathing and lung index, super oxide dismutase (SOD), malondialdehyde (MDA). The expression levels of C/EBPα were detected by immunohistochemistry. The expression levels of mTOR and S6K1 detected by flow cytometry. Western Blot was used to detect the proteins expression of NLRP3 and SirT1 pathway. Results In the model group, lung index and MDA were significantly higher and SOD was lower compared with the normal group; in the ginsenosides group, lung index and MDA were significantly lower and SOD was higher compared with the normal group (P < 0.05). Histopathological alterations presented broken alveolar wall, edema thickened alveolar septum in alveolar spaces and dust cells. Light microscopic analysis disclosed that lungs were less deteriorated in the ginsenosides group than in the model group. Ginsenoside reduced the level of C/EBPα, mTOR,S6K1 and NLRP3 and increased SirT1. Conclusions The protective effect of ginsenosides on AD-induced pulmonary edema and remodeling might be partly regulated by C/EBPα expression, mTOR, SirT1/NLRP3 signaling.