Roles Of Mesenchymal Stem Cells And SDF-1/CXCR4Axis On Asthma

Objective:(1) By comparing the content of mesenchymal stem cells (MSCs)in peripheral blood between normal rats and asthmatic rats, investigating the roleof MSCs on asthma.(2) By observing the expression of SDF-1and CXCR4among three groups, investigating the role of SDF-1and CXCR4on airwayinflammation and airway remodeling in asthma. The above experimental studyfor providing the experimental basis for later study in transplantingmesenchymal stem cells and exploring the role of mesenchymal stem cells onairway inflammation and airway remodeling in asthma and the relationship withSDF-1/CXCR4axis. Methods:（1）Eighteen SD female rats were randomlydivided into3groups (n=6): control group, asthmatic4weeks group andasthmatic8weeks group. The rats were sensitized and inhaled with ovalbumin(OVA) to make asthmatic model. After successfully established model ofasthma, the airway pressure had to be measured. The methods of HE stainingand Image-Pro Plus image analysis software were used to detect the changes of eosinophils granulocytes (EOS), the perimeter inner of the bronchial lumen, thewall area, the area of bronchial smooth muscle and the number of smoothmuscle cells of airway wall. Density gradient centrifugation was used to isolatemesenchymal stem cells in peripheral blood, while the content of mesenchymalstem cells could be detected by the flow cytometry. The Role of mesenchymalstem cells on airway inflammation and airway remodeling in asthma was able tobe analyzed from the above data.（2）RT-PCR and Western-blot were used todetect the expression of SDF-1and CXCR4in lung tissues among three groups.Immunohistochemistry was used to detect the expression of SDF-1in airwaywall in three groups. The Roles of SDF-1and CXCR4on airway inflammationand airway remodeling in asthma were able to be analyzed from the above data.Results:（1）The airway responsiveness, the count of EOS, the area of bronchialwall, the area of bronchial smooth muscle, the number of smooth muscle cells ofairway wall and the proportion of mesenchymal stem cells in the peripheralblood in the asthmatic4weeks group and asthmatic8weeks group weresignificantly higher than those in the control group（P<0.01或P<0.05）.Significant difference between two asthmatic groups was observed in the aboveindexes（P<0.01）. Pearson linear correlation demonstrated that the content ofmesenchymal stem cells were significantly positively correlated with the airwayresponsiveness, the number of EOS, the area of bronchial wall, the area ofbronchial smooth muscle and the number of smooth muscle cells of airway wall （P<0.001）.（2）RT-PCR showed that comparing with control group, theexpression of SDF-1and CXCR4in lung tissues in the asthmatic4weeks andasthmatic8weeks were significantly increased（P<0.01）. In addition, comparedwith asthmatic4weeks, the expression of SDF-1and CXCR4in lung tissues in8weeks asthmatic were significantly increased（P<0.01）. There is no differencein results between RT-PCR and Western-blot. Immunohistochemistrydemonstrated that comparing with control group, the expression of SDF-1inairway wall in the asthmatic4weeks and asthmatic8weeks were significantlyincreased（P<0.01）. In addition, compared with asthmatic4weeks, theexpression of SDF-1in airway wall in8weeks asthmatic was significantlyincreased. Pearson linear correlation demonstrated that the expression of SDF-1and CXCR4significantly positively correlated with the airway responsiveness,the number of EOS, the area of bronchial wall, the area of bronchial smoothmuscle and the number of smooth muscle cells of airway wall（P<0.001orP<0.01）. Conclusions:(1) Mesenchymal stem cells increased in asthma, whichmay involve in chronic airway inflammation and airway remodeling of asthma.(2) SDF-1/CXCR4plays a key role in asthma.