橘皮苷对百草枯诱导小鼠肺纤维化的干预作用及可能机制  

Intervention effect and possible mechanism of hesperidin on paraquat-induced pulmonary fibrosis in mice

作　　者：陈宏[1] 赵建云 张伟[1] 陈群[2] 王兵[3] CHEN Hong;ZHAO Jian-yun;ZHANG Wei;CHEN Qun;WANG Bing(The First Department of Pediatrics,the First Affiliated Hospital of Heilongjiang University of Chinese Medicine,Harbin 150040,China;Department of Clinical Laboratory,Harbin Acheng District People′s Hospital,Harbin 150300,China;School of Basic Medicine,Heilongjiang University of Chinese Medicine,Harbin 150400,China)

机构地区：[1]黑龙江中医药大学附属第一医院儿一科,哈尔滨市150040 [2]黑龙江省哈尔滨市阿城区人民医院检验科,哈尔滨市150300 [3]黑龙江中医药大学基础医学院,哈尔滨市150400

出　　处：《广西医学》2021年第14期1712-1716,1722,共6页Guangxi Medical Journal

基　　金：中国博士后科学基金第13批特别资助站中(2020T130178);黑龙江省中医药科研项目(ZHY19-004);黑龙江省博士后资助项目(LBH-Z15213)。

摘　　要：目的分析橘皮苷对百草枯诱导的小鼠肺纤维化的干预作用及可能机制。方法将60只雄性C57小鼠随机分为正常组、模型组、橘皮苷高剂量组、橘皮苷中剂量组、橘皮苷低剂量组和地塞米松组,每组10只。正常组给予生理盐水一次性灌胃,其余组各给予百草枯水溶液(100 mg/kg)一次性灌胃建模。建模1周后,地塞米松组给予腹腔注射地塞米松,橘皮苷高、中、低剂量组分别给予0.10 mL/10 g、0.06 mL/10 g、0.03 mL/10 g的橘皮苷灌胃,正常组及模型组均给予等容量的生理盐水。给药3周后,检测各组血清转化生长因子β1(TGF-β1)、肿瘤坏死因子α(TNF-α)、γ-干扰素水平,取肺组织观察组织病理变化,并检测肺组织丙二醛和髓过氧化物酶(MPO)水平、磷酸化蛋白激酶B(p-Akt)和磷酸化细胞外信号调节激酶(p-ERK)蛋白表达水平。结果(1)与正常组相比,模型组血清TGF-β1、TNF-α、丙二醛和MPO水平升高,血清γ-干扰素水平下降(均P<0.05);与模型组相比,橘皮苷不同剂量组和地塞米松组血清TGF-β1、TNF-α、丙二醛和MPO水平均降低,橘皮苷高/中剂量组和地塞米松组血清γ-干扰素水平均升高(均P<0.05);与地塞米松组、橘皮苷低/中剂量组相比,橘皮苷高剂量组的血清TGF-β1、TNF-α、丙二醛、MPO水平更低,γ干扰素水平更高(均P<0.05)。(2)模型组肺组织中p-Akt、p-ERK蛋白表达水平高于正常组(均P<0.05);与模型组相比,地塞米松组肺组织中p-Akt、p-ERK蛋白相对表达水平差异无统计学意义(P>0.05),橘皮苷不同剂量组肺组织中p-Akt、p-ERK蛋白相对表达水平降低(均P<0.05);橘皮苷高剂量组肺组织中p-Akt蛋白表达水平低于地塞米松组和其他剂量组,且p-ERK蛋白表达水平低于地塞米松组和橘皮苷低剂量组(均P<0.05)。结论橘皮苷对百草枯导致的小鼠肺纤维化具有改善作用,这可能与其抗氧化应激作用以及通过调控蛋白激酶B/细胞外信号调节激�Objective To analyze the intervention effect and possible mechanism of hesperidin on paraquat-induced pulmonary fibrosis in mice.Methods Sixty male C57 mice were randomly divided into normal group,model group,high-dose hesperidin group,medium-dose hesperidin group,low-dose hesperidin group and dexamethasone group,with 10 mice in each group.One-time intragastric administration of normal saline was performed on the normal group,and one-time intragastric administration of paraquat solution(100 mg/kg)was performed to develop a model in the remaining groups.After one week of modeling,the dexamethasone group received intraperitoneal injection of dexamethasone,while the high-,medium-and low-dose hesperidin groups received intragastric injection of hesperidin of 0.10 mL/10 g,0.06 mL/10 g and 0.03 mL/10 g,respectively,the normal and model groups were given the equivalent volume of normal saline.After three weeks of administration,serum levels of transforming growth factorβ1(TGF-β1),tumor necrosis factorα(TNF-α)and interferonγwere determined in all groups,lung tissues were removed for histopathological changes observation and detection of malondialdehyde level,myeloperoxidase(MPO)level,phosphorylated protein kinase B(p-Akt)protein expression level and phosphorylated extracellular signal-regulated kinase(p-ERK)protein expression level in lung tissues.Results(1)The model group exhibited higher serum TGF-β1,TNF-α,malondialdehyde and MPO levels and lower serum interferonγlevel than the normal group(all P<0.05);compared with the model group,the hesperidin groups and the dexamethasone group yielded decreased serum TGF-β1,TNF-α,malondialdehyde and MPO levels,and the high-and medium-dose hesperidin groups and the dexamethasone group yielded increased serum interferonγlevel(all P<0.05);compared with the dexamethasone group and the low-and medium-dose hesperidin groups,the high-dose hesperidin group possessed lower serum TGF-β1,TNF-α,malondialdehyde and MPO levels and higher interferonγlevel(all P<0.05).(2)The expressi

关 键 词：肺纤维化 百草枯 橘皮苷 炎症反应 氧化应激 蛋白激酶B/细胞外调节蛋白激酶通路 小鼠 

分 类 号：R563.9[医药卫生—呼吸系统]