关键词: AHR, Airway hyperresponsiveness ATP, Adenosine triphosphate Allergy BALF, Bronchoalveolar lavage fluid BM, Bone marrow CCL, Chemokine (C-C motif) ligand CD, Cluster of differentiation COX, Cyclooxygenase Cys-LT, Cysteinyl Leukotriene Cytb, Cytochrome b Drp1, Mitochondrial fission depends on the cytosolic GTPase dynamin-related protein 1 ELISA, Enzyme-linked immunosorbent assay FIS1, Mitochondrial fission 1 protein H&E, Haemotoxylin and eosin HGF, Hepatocyte growth factor HLA, Human leukocyte antigen HO, Heme oxygenase IDO, Indoleamine 2,3-dioxygenase IFN, Interferon IL, Interleukin IP, Intraperitoneal injection IT, Intratrachea administration Ig, Immunoglobulin Immune system Inflammation LT, Leukotriene MFN, Mitofusin MIP, macrophage inflammatory protein MMP, Matrix metalloproteinase MSC MSC, mesenchymal stem cell MSC/BI, mesenchymal stem cell bronchial administration MSC/IV, mesenchymal stem cell intravenous injection ND1, NADH-ubiquinone oxidoreductase chain 1 NO, Nitric oxide Nrf, Nuclear erythroid 2 p45-related factor OPA1, Mitochondrial dynamin like GTPase OVA, Ovalbumin PAS, Periodic-acid-Schiff PBS, Phosphate-buffered saline PGC1a, Peroxisome proliferator-activated receptor gamma coactivator 1-alpha PGE2, Prostaglandin E2 ROS, Reactive oxygen species TFAM, Transcription factor A mitochondrial TGF, Transforming growth factor TNF, Tumor necrosis factor Th, T helper iPSC, induced pluripotent stem cells

来  源:   DOI:10.1016/j.sjbs.2021.07.071   PDF(Pubmed)

Abstract:
Asthma is a complicated lung disease, which has increased morbidity and mortality rates in worldwide. There is an overlap between asthma pathophysiology and mitochondrial dysfunction and MSCs may have regulatory effect on mitochondrial dysfunction and treats asthma. Therefore, immune-modulatory effect of MSCs and mitochondrial signaling pathways in asthma was studied. After culturing of MSCs and producing asthma animal model, the mice were treated with MSCs via IV via IT. BALf\'s eosinophil Counting, The levels of IL-4, -5, -13, -25, -33, INF-γ, Cys-LT, LTB4, LTC4, mitochondria genes expression of COX-1, COX-2, ND1, Nrf2, Cytb were measured and lung histopathological study were done. BALf\'s eosinophils, the levels of IL-4, -5, -13, -25, -33, LTB4, LTC4, Cys-LT, the mitochondria genes expression (COX-1, COX-2, Cytb and ND-1), perivascular and peribronchial inflammation, mucus hyper-production and hyperplasia of the goblet cell in pathological study were significantly decreased in MSCs-treated asthma mice and reverse trend was found about Nrf-2 gene expression, IFN-γ level and ratio of the INF-γ/IL-4. MSC therapy can control inflammation, immune-inflammatory factors in asthma and mitochondrial related genes, and prevent asthma immune-pathology.
摘要:
哮喘是一种复杂的肺部疾病,这在全球范围内增加了发病率和死亡率。哮喘的病理生理学与线粒体功能障碍存在重叠,MSCs可能对线粒体功能障碍具有调节作用并治疗哮喘。因此,研究了MSCs和线粒体信号通路在哮喘中的免疫调节作用。在培养MSCs并产生哮喘动物模型后,通过IV通过IT用MSC治疗小鼠。BALf的嗜酸性粒细胞计数,IL-4、-5、-13、-25、-33、INF-γ、Cys-LT,检测LTB4,LTC4,线粒体COX-1,COX-2,ND1,Nrf2,Cytb基因的表达,并进行肺组织病理学研究。BALf的嗜酸性粒细胞,IL-4、-5、-13、-25、-33、LTB4、LTC4、Cys-LT、线粒体基因表达(COX-1,COX-2,Cytb和ND-1),血管周围和支气管周围炎症,病理研究中杯状细胞的粘液过度产生和增生在MSCs治疗的哮喘小鼠中明显减少,发现Nrf-2基因表达呈逆转趋势,IFN-γ水平和INF-γ/IL-4的比率。MSC治疗可以控制炎症,哮喘免疫炎症因子与线粒体相关基因,预防哮喘免疫病理。
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