葡萄皮籽提取物对人工细颗粒物诱导的自发性高血压大鼠肺损伤保护作用探究  

Protective effect of grape skin seed extract against lung injuries induced by artificial fine particles matters in spontaneoushypertension rats

作　　者：刘志刚 李思铮 江海燕 旷煉 靳洪涛 包捷 李静 LIU Zhi-gang;LI Si-zheng;JIANG Hai-yan;KUANG Lian;JIN Hong-tao;BAO Jie;LI Jing(School of Biology and Biological Engineering,South China University of Technology,Guangzhou Guangdong 510006,China;Guangdong Provincial People's Hospital,Guangdong Academy of Medical Sciences,Guangzhou Guangdong 510080,China;New Drug Safety Evaluation Center,Institute of Materia Medica,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050,China;Beijing Union-Genius Pharmaceutical Technology Co.,Ltd,Beijing 100176,China)

机构地区：[1]华南理工大学生物科学与工程学院,广东广州510006 [2]广东省人民医院(广东省医学科学院),广东广州510080 [3]中国医学科学院药物研究所新药安全性评价研究中心,北京100050 [4]北京协和建昊医药技术开发有限责任公司,北京100176

出　　处：《毒理学杂志》2022年第4期297-303,共7页Journal of Toxicology

基　　金：国家自然科学基金(82074104);高血压病研究北京市重点实验室开放课题(2019GXY-KFKT-04)。

摘　　要：目的探究葡萄皮籽提取物对人工细颗粒诱导的自发性高血压大鼠(SHR)肺损伤的保护作用。方法将30只自发性高血压大鼠随机分为对照组、模型组和药物组。对照组气管滴注生理盐水,模型组与药物组气管滴注人工细颗粒物,50 mg/kg·bw,1次/周,共15周。采用全身体积描记系统及振荡式肺功能检测系统检测其肺功能;智能无创血压计测定各组大鼠血压;试验结束时收集各组大鼠全血进行血细胞分析、肺泡灌洗液进行炎症因子检测;收集肺组织进行苏木素-伊红(HE)染色并检测3组之间的抗氧化能力及DNA损伤情况。结果试验结束时,各组动物血压均较正常大鼠明显升高,组间无差异。与对照组相比,模型组肺功能明显下降;肺组织慢性炎症及纤维增生明显;单核细胞比率与中性粒细胞比率升高;肺泡灌洗液中IL-1β、TNF-α及IL-12p70升高;肺组织SOD活性下降,MDA与8-OHdG含量升高,OGG1基因表达量降低,差异具有统计学意义(P<0.05)。与模型组相比,药物组肺功能回调明显;肺组织以慢性炎症和渗出为主要病理变化;全血单核细胞比率与中性粒细胞比率降低;肺泡灌洗液中IL-1β、TNF-α及IL-12p70降低;肺组织SOD活力升高,MDA、8-OHdG含量降低,OGG1基因表达升高(P<0.05)。结论自发性高血压大鼠长期染毒人工细颗粒物可造成明显的肺损伤,后期呈间质肺纤维化状态,葡萄皮籽提取物可有效改善大鼠肺损伤状态,这可能与葡萄皮籽提取物降低人工细颗粒物诱导的氧化应激和提高DNA损伤的修复有关,值得进一步探索研究。Objective To investigate the protective effect of grape skin seed extract against lung injuries induced by artificial fine particles in spontaneous hypertension rats.Methods Thirty spontaneous hypertensive rats were randomly divided into control,model and drug group.The control group was endotracheally dripped with normal saline,the model and the drug group were endotracheally dripped with artificial fine particles,50 mg/kg·bw,once a week,for 15 weeks.Lung functions were detected by systemic plethysmography system and oscillatory pulmonary function detection system.Using intelligent noninvasive sphygmomanometer to measure the blood pressure of rats in each group.Collecting the whole blood for blood cell analysis and bronchial alveolar lavage fluid(BALF)for inflammatory factors measurement.Lung tissues were collected for HE staining,detecting the antioxidant capacity and DNA damage was detected among the three groups.Results The blood pressure of animals in each group were significantly higher than those of normal rats,and there were no differences between the groups.Compared with the control group,lung function of the model group decreased significantly;Lung tissue chronic inflammation and fibrous hyperplasia were obvious;The ratio of monocytes and neutrophils increased.The levels of IL-1β,TNF-αand IL-12p70 in BALF increased.SOD activity decreased,MDA and 8-OHdG contents increased,and OGG1 gene expression decreased in lung tissues,and there were significant differences(P<0.05).Compared with the model group,the pulmonary function recovered significantly in the drug group.The main pathological changes of lung tissue were relieved,mainly chronic inflammation and exudation.The ratio of whole blood monocytes and neutrophils decreased.The levels of IL-1β,TNF-αand IL-12p70 in BALF decreased.SOD activity increased,MDA and 8-OHdG content decreased,and OGG1 gene expression increased in lung tissues(P<0.05).Conclusion Spontaneous hypertensive rats exposed to artificial fine particles for a long time could cause signifi

关 键 词：葡萄皮籽提取物 细颗粒物 肺损伤 保护作用 

分 类 号：R114[医药卫生—卫生毒理学] R99[医药卫生—公共卫生与预防医学]