摘要
目的探讨去氢骆驼蓬碱对细粒棘球蚴继发感染引起的小鼠肺纤维化的组织病理改变及TGF-β_(1)、Smad3和NF-кB p65表达的影响。方法取雌性昆明种小鼠,随机分为空白对照组与实验组,对实验组小鼠腹腔注射细粒棘球蚴建立包虫病动物模型。将造模成功的小鼠分为模型组、去氢骆驼蓬碱(HM)治疗组及阿苯达唑(ABZ)治疗组。药物治疗28 d后,取各组小鼠肺脏制作组织切片进行HE染色和Masson染色,观察肺组织病理变化和胶原沉积情况。分别采用实时荧光定量PCR法、免疫组织化学法和Western blot检测肺组织中TGF-β_(1)、Smad3及NF-кB p65的表达水平。结果HE和Masson染色显示,细粒棘球蚴可导致小鼠肺纤维化。与空白对照组相比,模型组小鼠炎症加重,肺泡间隔增厚,有炎性细胞浸润,并出现大量蓝色胶原沉积;与模型组相比,ABZ治疗组和HM治疗组小鼠肺泡结构较完整,炎症程度和胶原沉积较轻,肺泡间隔增生程度较轻,以HM治疗组减轻更明显。qRT-PCR检测模型小鼠肺组织中TGF-β_(1)mRNA、Smad3 mRNA及NF-кB p65 mRNA水平均显著高于正常对照组(F值分别为111.880、40.102和90.132,均P<0.01);与模型组相比,ABZ治疗组与HM治疗组小鼠肺组织中TGF-β_(1)mRNA、Smad3 mRNA及NF-кB p65 mRNA水平均显著降低(F值分别为75.454、26.173和44.417,均P<0.01),以HM治疗组下降更显著(F值分别为21.397、34.362和10.355,均P<0.05)。免疫组化检测模型组小鼠肺组织中TGF-β_(1)、Smad3及NF-кB p65的表达量显著高于正常对照组(F值分别为604.937、318.739和217.211,均P<0.01);ABZ治疗组和HM治疗组小鼠肺组织中TGF-β_(1)、Smad3和NF-кB p65的表达均有下降趋势,以HM治疗组下降更显著(F值分别为77.562、40.476和21.093,均P<0.01)。Western blot检测ABZ和HM治疗组小鼠TGF-β_(1)、Smad3和NF-кB p65蛋白水平较模型组显著下调(F值分别为27.718、74.676和181.742,均P<0.01),以HM治疗组下调更显著。结论小�
Objective To investigate the effects of harmine on histopathological changes and expression of TGF-β1,Smad3,and NF-кB p65 in mice with pulmonary fibrosis induced by an Echinococcus granulosus secondary infection.Methods Female Kunming mice were randomly divided into a blank control group and an experimental group.Mice in the experimental group were intraperitoneally injected with E.granulosus to establish an animal model of echinococcosis.The mice were divided into a model group,a harmine(HM)treatment group,and an albendazole(ABZ)treatment group.After 28 days of drug treatment,lungs of mice in each group were used to prepare tissue sections for HE staining and Masson staining to observe pathological changes and collagen deposition.The levels of TGF-β_(1),Smad3,and NF-кB p65 expression in lung tissues were determined using real-time quantitative PCR,immunohistochemistry,and Western blotting.Results HE and Masson staining indicated that E.granulosus induced pulmonary fibrosis in mice.Compared to the control group,the inflammation in the model group was aggravated,the alveolar septum thickened,inflammatory cells infiltrated the lungs,and a large number of blue collagen deposits were evident.Compared to the model group,the alveolar structure of mice in the ABZ and HM treatment groups was more intact,the degree of inflammation and collagen deposition was lower,and the degree of alveolar septal hyperplasia was lower.The degree of fibrosis in the HM treatment group decreased significantly.qRT-PCR results indicated that the levels of expression of TGF-β_(1)mRNA,Smad3 mRNA,and NF-кB p65 mRNA in the lung tissues of model mice were significantly higher than levels in the normal control group(F-values of 111.880,40.102 and 90.132,respectively;P<0.01 for all);Compared to model group,the levels of TGF-β_(1)mRNA,Smad3 mRNA and NF-кB p65 mRNA in the ABZ group and HM group decreased significantly(F-values of 75.454,26.173 and 44.417,respectively;P<0.01 for all),and the decrease was more significant in the HM group(F-value
作者
吾斯曼江·艾麦提
巩月红
马瑞佳
赵美玲
张莉
王建华
WusimanjiangAimaiti;GONG Yue-hong;MA Rui-jia;ZHAO Mei-ling;ZHANG Li;WANG Jian-hua(College of Pharmacy,Xinjiang Medical University,Urumqi,Xinjiang 83000,China;Pharmacy,First Hospital Affiliated with Xinjiang Medical University;State Key Laboratory of Pathogenesis,Prevention and Treatment of Middle and Subtropical High Jointly Built by Xinjiang Medical University)
出处
《中国病原生物学杂志》
CSCD
北大核心
2021年第12期1414-1419,共6页
Journal of Pathogen Biology
基金
国家自然科学基金项目(No.81860666)
新疆维吾尔自治区自然科学基金项目(No.2020D01C240,2021D01D15)
新疆重大疾病防治与转化协同创新中心资助项目(No.80910721)
省部共建中亚高发病成因与防治国家重点实验室开放课题(No.SKL-HIDCA-2020-1)。
