红景天苷注射液对脂多糖诱导脓毒性休克肺损伤大鼠肺血管通透性的影响

doi:10.12092/j.issn.1009-2501.2019.11.007

摘要/Abstract

摘要：

目的:探讨红景天苷注射液对脂多糖诱导脓毒性休克肺损伤大鼠肺血管通透性的影响。方法:75只SD大鼠随机分为对照组、模型组、阳性对照组、Sal-L组、Sal-H组，对照组不予任何处理，模型组通过脂多糖造模，阳性对照组造模后给予5 mg/kg地塞米松，Sal-L组、Sal-H组造模后分别给予0.68、1.09 ng/kg红景天苷注射液，比较各组肺组织病理学、肺损伤评分（LIS）、肺湿/干质量比（W/D）、肺通透指数（LPI）、肺组织中伊文思蓝含量、氧化应激指标［髓过氧化物酶活性（MPO）、丙二醛（MDA）、超氧化物岐化酶（SOD）］、炎症指标［白介素（IL）-1、IL-6、肿瘤坏死因子-α（TNF-α）、核因子κB（NF-κB）、磷酸化NF-κB p65（p-NF-κB p65）、NF-κB抑制蛋白IκBa磷酸化蛋白（p-IκBa）］表达。结果:对照组双肺无异常；模型组大鼠一般情况、肺部出现明显病理变化，阳性对照组、Sal-L组、Sal-H组较模型组不同程度改善。与模型组相比，Sal-L组、Sal-H组LIS、W/D、LPI呈剂量依赖性降低（P＜0.05）。与模型组相比，Sal-L组、Sal-H组肺组织中伊文思蓝含量呈剂量依赖性降低（P＜0.05）。与模型组相比，Sal-L组、Sal-H组MPO、MDA呈剂量依赖性降低，SOD呈剂量依赖性升高（P＜0.05）。与模型组相比，Sal-L组、Sal-H组IL-1、IL-6、TNF-α、NF-κB mRNA及p-NF-κB p65、p-IκBa蛋白呈剂量依赖性降低（P＜0.05）。结论:红景天苷注射液可改善脓毒症休克肺损伤大鼠肺血管通透性，减轻肺水肿，其机制可能与抗氧化应激，抑制炎症反应有关。

关键词: 红景天苷注射液, 脂多糖, 脓毒性休克, 肺损伤, 肺血管通透性

Abstract:

AIM: To investigate the effects of salidroside injection on pulmonary vascular permeability in rats with septic shock induced lung injury induced by lipopolysaccharide. METHODS: Seventy-five Sprague-Dawley rats were randomly divided into control group, model group, positive control group, Sal-L group and Sal-H group. The control group did not receive any treatment. The model group was modeled by lipopolysaccharide, and the positive control group was modeled. After administration of 5 mg/kg dexamethasone, Sal-L group and Sal-H group were given 0.68 and 1.09 ng/kg salidroside injection, respectively. The lung histopathology and lung injury score (LIS) were compared, as well as lung wet/dry mass ratio (W/D), lung permeability index (LPI), Evans blue content in lung tissue, oxidative stress index ［myeloperoxidase activity (MPO), malondialdehyde (MDA) , superoxide dismutase (SOD)］, inflammation indicators ［interleukin (IL)-1, IL-6, tumor necrosis factor-α (TNF-α), nuclear factor κB (NF-κB), phosphorylated NF-κB p65 (p-NF-κB p65), NF-κB inhibitor protein IκBa phosphorylated protein (p-IκBa)］ expression. RESULTS:There were no abnormalities in the lungs of the control group; the general condition and the pathological changes in the lungs were observed in the model group, and the positive control group, the Sal-L group and the Sal-H group were improved to some extents compared with the model group. Compared with the model group, the LIS, W/D, and LPI in the Sal-L group and the Sal-H group were decreased in a dose-dependent manner (P＜0.05). Compared with the model group, the content of Evans blue in the tissue in Sal-L group and Sal-H group decreased in a dose-dependent manner (P＜0.05). Compared with the model group, the MPO and MDA in the Sal-L group and the Sal-H group decreased in a dose-dependent manner, and the SOD was dose-dependently elevated (P＜0.05). Compared with the model group, IL-1, IL-6, TNF-α, NF-κB mRNA and p-NF-κB p65, p-IκBa protein in Sal-L group and Sal-H group was decreased in a dose-dependent manner (P＜0.05). CONCLUSION: Salidroside injection can improve pulmonary vascular permeability and reduce pulmonary edema in rats with septic shock and lung injury. The mechanism may be related to anti-oxidative stress and inhibition of inflammatory response.

Key words: salidroside injection, lipopolysaccharide, septic shock, lung injury, pulmonary vascular permeability

中图分类号:

陈少忠，林梅瑟，程黎民，朱乐乐. 红景天苷注射液对脂多糖诱导脓毒性休克肺损伤大鼠肺血管通透性的影响[J]. 中国临床药理学与治疗学, 2019, 24(11): 1256-1262.

CHEN Shaozhong, LIN Meise, CHENG Limin, ZHU Lele. Effects of salidroside injection on pulmonary vascular permeability in rats with septic shock induced lung injury induced by lipopolysaccharide[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(11): 1256-1262.

参考文献

［1］Chen X, Wang T, Song L, et al. Activation of multiple Toll-like receptors serves different roles in sepsis-induced acute lung injury［J］. Exp Ther Med, 2019, 18(1): 443-450.
［2］Zhou J, Fu Y, Liu K, et al. miR-206 regulates alveolar type II epithelial cell Cx43 expression in sepsis-induced acute lung injury［J］. Exp Ther Med, 2019, 18(1): 296-304.
［3］Shashaty MGS, Reilly JP, Faust HE, et al. Plasma receptor interacting protein kinase-3 levels are associated with acute respiratory distress syndrome in sepsis and trauma: a cohort study［J］. Crit Care, 2019, 23(1): 235.
［4］Shen Y, Song J, Wang Y, et al. M2 macrophages promote pulmonary endothelial cells regeneration in sepsis-induced acute lung injury［J］. Ann Transl Med, 2019, 7(7): 142.
［5］刘萌萌, 李彦文, 周庆彪, 等. 氯气吸入致大鼠肺血管内皮细胞的线粒体损伤及红景天苷的干预作用［J］. 癌变·畸变·突变, 2018, 30(1): 31-36,41.
［6］罗葵, 曹丽歌, 高丽芳, 等. 红景天片提高缺氧耐受力的功能研究［J］. 食品研究与开发, 2016, 37(17): 158-160.
［7］韩悦, 史佳, 吴丽丽, 等. PI3K/Akt/Nrf2信号通路在电针刺减轻兔内毒素休克诱发急性肺损伤中的作用［J］. 中国中西医结合外科杂志, 2018, 24(2): 197-202.
［8］王平, 吴惠玲, 朱娱, 等. 水通道蛋白亚型3在脓毒症肺血管通透性中的作用及SS-31对其的影响［J］. 第三军医大学学报, 2017, 39(2): 111-115.
［9］Li L, Shu MQ, Chen J. CYLD deficiency exacerbates lipopolysaccharide (LPS)-induced pyroptosis in astrocytes of mice with sepsis［J］. Biochem Biophys Res Commun, 2019, 514(4): 1066-1073.
［10］Cai X, Chen Y, Xie X, et al. Astaxanthin prevents against lipopolysaccharide-induced acute lung injury and sepsis via inhibiting activation of MAPK/NF-κB［J］. Am J Transl Res, 2019, 11(3): 1884-1894.
［11］Wang J, Fan SM, Zhang J. Epigallocatechin-3-gallate ameliorates lipopolysaccharide- induced acute lung injury by suppression of TLR4/NF-κB signaling activation ［J］. Braz J Med Biol Res, 2019, 52(7): e8092.
［12］Krebs J, Hillenbrand A, Tsagogiorgas C, et al. Intravenous delivery of granulocyte-macrophage colony stimulating factor impairs survival in lipopolysaccharide- induced sepsis ［J］. PLoS One, 2019, 14(6): e0218602.
［13］王晓鹏, 陈腾飞, 罗丹, 等. 基于不同辨证体系的脓毒症休克中医病机探析［J］. 中国中医急症, 2018, 27(1): 101-104.
［14］张新茹, 于玲, 王冬雪, 等. 红景天苷通过micro RNA-370改善2型糖尿病小鼠糖代谢的作用机制［J］. 医药导报, 2018, 37(3): 279-284.
［15］Lan KC, Chao SC, Wu HY, et al. Salidroside ameliorates sepsis-induced acute lung injury and mortality via downregulating NF-κB and HMGB1 pathways through the upregulation of SIRT1［J］. Sci Rep, 2017, 7(1): 12026.
［16］Huang LY, Yen IC, Tsai WC, et al. Rhodiola crenulata attenuates high glucose induced endothelial dysfunction in human umbilical vein endothelial cells ［J］. Am J Chin Med, 2017, 45(6): 1201-1216.
［17］Blet A, Deniau B, Geven C, et al. Adrecizumab, a non-neutralizing anti-adrenomedullin antibody, improves haemodynamics and attenuates myocardial oxidative stress in septic rats［J］. Inten Care Med Exp, 2019, 7(1):25.
［18］Liu Q, Xie J, Yang Y. Advances in the regulation mechanism of cholinergic anti-inflammatory pathway on sepsis ［J］. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue, 2019, 31(6): 781-784.
［19］Molinaro R, Anna Pastò, Corbo C, et al. Macrophage-derived nanovesicles exert intrinsic anti-inflammatory properties and prolong survival in sepsis through a direct interaction with macrophages ［J］. Nanoscale, 2019, 11(28): 13576-13586.
［20］Zusso M, Lunardi V, Franceschini D, et al. Ciprofloxacin and levofloxacin attenuate microglia inflammatory response via TLR4/NF-κB pathway ［J］. J Neuroinflammation, 2019, 16(1): 148.
［21］Ding Y, Feng Q, Chen J, et al. TLR4/NF-κB signaling pathway gene single nucleotide polymorphisms alter gene expression levels and affect ARDS occurrence and prognosis outcomes ［J］. Medicine (Baltimore), 2019, 98(26): e16029.
［22］Zhao C, Wang Y, Yuan X, et al. Berberine inhibits lipopolysaccharide-induced expression of inflammatory cytokines by suppressing TLR4-mediated NF-κB and MAPK signaling pathways in rumen epithelial cells of Holstein calves ［J］. J Dairy Res, 2019, 86(2): 171-176.
［23］Guo NF, Cao YJ, Chen X, et al. Lixisenatide protects doxorubicin-induced renal fibrosis by activating NF-κB/TNF-α and TGF-β/Smad pathways ［J］. Eur Rev Med Pharmacol Sci, 2019, 23(9): 4017-4026.
［24］Zhou CN, Yao W, Gong YN, et al. 22-oxacalcitriol protects myocardial ischemia-reperfusion injury by suppressing NF-κB/TNF-α pathway ［J］. Eur Rev Med Pharmacol Sci, 2019, 23(12): 5495-5502.

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