机构地区:[1]台州恩泽医疗中心(集团)路桥医院呼吸与危重症学科,浙江台州318050 [2]台州恩泽医疗中心(集团)路桥医院高压氧中心 [3]台州恩泽医疗中心(集团)恩泽医院检验科
出 处:《中国药师》2020年第6期1069-1072,1090,共5页China Pharmacist
基 金:台州市科技计划项目(编号:1902ky69)。
摘 要:目的:探讨黄芩总黄酮对慢性阻塞性肺疾病(COPD)大鼠炎症和氧化应激的影响及机制。方法:40只SD大鼠用随机数字表法分为4组:正常对照组、模型组、黄芩总黄酮低(25 mg·kg^-1)、高(50 mg·kg^-1)组,每组10只。除正常对照组外,其余各组采用熏烟联合气管内注入脂多糖(LPS)的方法建立COPD模型,建模第15天开始,黄芩总黄酮低、高剂量组大鼠分别灌胃给予黄芩总黄酮,灌胃体积10 ml·kg^-1,正常对照组和模型组给予等量生理盐水,连续20 d。末次给药24 h后麻醉处死大鼠,对大鼠支气管肺泡灌洗液(BALF)中炎性细胞进行分类,对肺组织进行病理学检查,检测白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、丙二醛(MDA)、超氧化物歧化酶(SOD)、沉默信息调节因子-1(SIRT1)和过氧化物酶体增殖活化受体γ共激活因子-1α(PGC-1α)表达水平。结果:正常对照组大鼠肺泡结构清楚,无炎性细胞浸润痕迹;模型组大鼠出现严重的炎症反应,肺泡囊和肺泡腔增大,肺泡壁增厚;黄芩总黄酮各剂量组大鼠炎症细胞浸润程度有所减轻,肺泡囊和肺泡间隙减轻,且呈剂量依赖性。与正常对照组相比,其余各组大鼠巨噬细胞百分比、中性粒细胞百分比、IL-6、IL-8、MDA含量增高,淋巴细胞百分比、SOD、SIRT1和PGC-1αmRNA水平降低(P<0.05);与模型组相比,各黄芩总黄酮剂量组大鼠巨噬细胞百分比、中性粒细胞百分比、IL-6、IL-8、MDA含量降低,淋巴细胞百分比、SOD、SIRT1和PGC-1αmRNA水平增高,且呈剂量依赖性(P<0.05)。结论:黄芩总黄酮可能通过激活SIRT1/PGC-1α信号通路,减轻COPD大鼠炎症和氧化应激,发挥对COPD的治疗作用。Objective:To investigate the effects of total flavonoids from Scutellaria baicalensis Georgi on the inflammation and oxidative stress in rats with chronic obstructive pulmonary disease(COPD)by regulating SIRT1/PGC-1αsignal pathway.Methods:Forty SD rats were divided into 4 groups by random number table method:the normal control group,the model group,and total flavonoids of Scutellaria baicalensis Georgi low(25 mg·kg^-1)and high(50 mg·kg^-1)groups with 10 rats in each group.Except the normal control group,the other groups were established COPD model by smoke and lipopolysaccharide(LPS)intratracheal injection.From the 15th day of modeling,the rats in Scutellaria baicalensis Georgi low and high groups were administered orally with the corresponding dose of drug,the volume of which was 10 ml·kg^-1,and the normal control group and the model group were given the same amount of normal saline for 20 consecutive days.The rats were anesthetized and killed at 24 h after the last dose,the inflammatory cells in bronchoalveolar lavage(BALF)were classified and lung histopathology was examined.The expression levels of interleukin-6(IL-6),interleukin-8(IL-8),malondialdehyde(MDA),superoxide dismutase(SOD),silent information regulator-1(SIRT1)and peroxidosome proliferactivated receptor-γcoactivator-1α(PGC-1α)were detected.Results:In the normal control group,the alveolar structure was clear,and there was no sign of inflammatory cell infiltration.In the model group,there was serious inflammatory reaction,and the alveolar sac and alveoli cavity increased,and the alveoli wall thickened.In each dose group of total flavonoids from Scutellaria baicalensis Georgi,the degree of inflammatory cell infiltration decreased,and the alveolar sac and alveoli space decreased in a dose-dependent manner.Compared with those in the normal control group,the percentage of macrophages,percentage of neutrophils,and contents of IL-6,IL-8 and MDA in the other groups were increased,and the percentage of lymphocytes and the levels of SOD,SIRT1 and PGC-1α
关 键 词:黄芩总黄酮 沉默信息调节因子-1/过氧化物酶体增殖活化受体γ共激活因子-1α信号通路 慢性阻塞性肺疾病 炎症 氧化应激
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