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转录组分析探索汉喘祖帕颗粒缓解大鼠哮喘的分子机制

Transcriptomic Analysis Exploring the Molecular Mechanisms of Hanchuan Zupa Granules in Alleviating Asthma in Rat.

作者信息

Yin Hailong, Fan Yanbo, Mu Dandan, Song Fei, Tian Fang, Yin Qiang

机构信息

Research and Development Department, Xinjiang Uygur Pharmaceutical Co., Ltd., Wulumuqi, Xinjiang 830001, China.

Science and Education Department, Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430014, China.

出版信息

Evid Based Complement Alternat Med. 2021 Jul 2;2021:5584099. doi: 10.1155/2021/5584099. eCollection 2021.

Abstract

OBJECTIVE

To investigate the molecular mechanisms of HCZP treatment of asthma.

MATERIALS AND METHODS

Thirty Sprague Dawley (SD) rats were divided into normal, asthma, and HCZP groups ( = 10). The asthma model was sensitized by 1 mg ovalbumin (OVA)/aluminum hydroxide Al(OH)mixture and then challenged with 1% aerosolized OVA for four weeks. Rats in the HCZP group received 10.08 g/kg/d HCZP for four weeks during OVA challenge. Then, lung tissues of rats in each group were collected for RNA sequencing. Moreover, the expression level of some core genes was detected by using western blotting and immunohistochemistry.

RESULTS

Inflammatory cell infiltration and pathological damage of the lungs improved in the HCZP group. Compared with the asthma group (0.049 ± 0.002 mm/mm; 0.036 ± 0.006 mm/mm; and 0.014 ± 0.001 mm/mm), total wall thickness (0.042 ± 0.001 mm/mm), inner wall thickness (0.013 ± 0.001 mm/mm), and smooth muscle layer thickness (0.012 ± 0.001 mm/mm) significantly decreased in the HCZP group. Bioinformatics analysis showed that hub genes such as bradykinin receptor B2 (Bdkrb2) and CD4 molecule (Cd4) had different expression patterns between model and HCZP groups. Two transcription factors, forkhead box Q1 (Foxq1) and nuclear factor of activated T cells 2 (Nfatc2), served important regulatory roles in asthma. Compared with the model group, Bdkrb2 protein expression increased and Nfatc2 protein expression decreased in the HCZP group. . HCZP could alleviate asthma via regulating the expression of several hub genes, which might serve as therapeutic targets for asthma. However, the mechanism of these genes will be studied in the future.

摘要

目的

探讨黄芪总皂苷(HCZP)治疗哮喘的分子机制。

材料与方法

将30只Sprague Dawley(SD)大鼠分为正常组、哮喘组和HCZP组(每组10只)。哮喘模型通过1mg卵清蛋白(OVA)/氢氧化铝Al(OH)混合物致敏,然后用1%雾化OVA激发4周。HCZP组大鼠在OVA激发期间接受10.08g/kg/d的HCZP治疗4周。然后,收集每组大鼠的肺组织进行RNA测序。此外,采用蛋白质免疫印迹法和免疫组织化学法检测一些核心基因的表达水平。

结果

HCZP组肺组织炎症细胞浸润和病理损伤有所改善。与哮喘组(0.049±0.002mm/mm;0.036±0.006mm/mm;0.014±0.001mm/mm)相比,HCZP组总壁厚度(0.042±0.001mm/mm)、内壁厚度(0.013±0.001mm/mm)和平滑肌层厚度(0.012±0.001mm/mm)显著降低。生物信息学分析表明,缓激肽受体B2(Bdkrb2)和CD4分子(Cd4)等枢纽基因在模型组和HCZP组之间具有不同的表达模式。两种转录因子,叉头框Q1(Foxq1)和活化T细胞核因子2(Nfatc2),在哮喘中起重要调节作用。与模型组相比,HCZP组Bdkrb2蛋白表达增加,Nfatc2蛋白表达降低。HCZP可通过调节多个枢纽基因的表达来缓解哮喘,这些基因可能作为哮喘的治疗靶点。然而,这些基因的作用机制将在未来进行研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df93/8275397/1c7773f02396/ECAM2021-5584099.001.jpg

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