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The Role Of Rho/ROCK Signaling Pathway In Airway Remodeling Of Bronchial Asthma

Posted on:2019-09-01Degree:MasterType:Thesis
Country:ChinaCandidate:C J HuangFull Text:PDF
GTID:2404330572467636Subject:Internal medicine
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Objective: 1.To explore the clinical significance of ROCK2 in bronchial asthma by detecting the content of serum ROCK2 in asthmatic patients.2.To investigate mechanism of airway remodeling via the effect of Rock2 inhibitor on the expression of Rock2,MLCK and VEGF in asthmatic mice.Methods: 1.40 asthma patients and 40 healthy people were randomly selected.The content of serum ROCK2,the pulmonary function and percentage of eosinophils in sputum,and severity of the asthma group patients were measured for the members of the two groups.2.30 BALB/c mice were randomly divided into three groups: control group,asthma group and Y27632 group,10 in each group.Model was sensitized and established by OVA induction.He staining was used to observe the pathological changes of lung tissue in mice.Enzyme linked immunosorbent assay(ELISA)determined serum OVA-s Ig E levels,the expression of ROCK2,MLCK and VEGF in bronchoalveolar lavage fluid.The m RNA levels of ROCK2,MLCK and VEGF in the lung tissue were determined by RT-PCR.The perimeter of bronchial lumen(PBM),the wall area of bronchial tube(WAt)and the wall area of bronchial smooth muscle(WAm)were measured by medical image analysis software and standardized by PBM.The data were analyzed by one-way ANOVA,and the LSD-t method was used to compare the differences between two groups,P <0.05 is statistically significant.Results: The content of serum ROCK2(5.55±1.15ng/ml)in control group was apparently higher than the asthma group(37.59±6.63ng/ml),(p<0.05).The mean pulmonary function of asthma group was significantly lower than those in health group(P < 0.05).serum levels of ROCK2 passively corrected with the pulmonary function FEV1(%predicted)(r=-0.96,p<0.001),positively corrected with the asthma severity gradation(rs=0.819,p<0.001),respectively,while no significant correlation was found between serum levels of ROCK2 with percentage of eosinophils in sputum.Asthmatic mice experimental research showed: He staining showed that the bronchial wall of mice in asthma group was thickened,and a large number of inflammatory cells were infiltrated around the bronchi,but those in Y27632 group were significantly attenuated.The serum level of OVA-s Ig Ein asthma group [(137.84±23.96)ng/ml] is apparently higher than those in control group[(33.02±9.27)ng/ml],(p<0.05),while,the serum level of OVA-s Ig E in Y27632 group [(57.89±14.90)ng/ml] is lower than those in asthma group(p<0.05).The levels ROCK2,MLCK and VEGF in BALF showed that asthma group [(52.46±10.17?103.62±11.98?57.09±20.82)ng/ml,respectively] were much higher than the levels ROCK2,MLCK and VEGF in BALF of control group mice [(24.40±6.13?40.46±10.75?36.54±15.98)ng/ml](all p<0.05).The levels ROCK2,MLCK and VEGF in Y27632 group[(32.87±8.95?57.36±8.50?38.46±9.22)ng/ml,respectively] were lower than the levels that in asthma group mice(all p<0.05).the m RNA levels of ROCK2,MLCK and VEGF in lung tissue showed that asthma group(4.37±1.51 ? 5.44±2.11 ?5.51±1.34,respectively)were higher than the levels that in control group(1.03±0.38?1.18±0.45 ? 2.12±0.62,respectively),(all p<0.05),while the m RNA levels of ROCK2,MLCK and VEGF in Y27632 group(2.67±1.75 ? 2.04±1.19 ?2.75±0.99,respectively)were all lower than index that in asthma group.The medical image analysis software showed that WAt/PBM,WAm/PBM in asthma group mice [(17.4±3.81?8.24±1.85)?m,respectively] were significantly higher than those in control group mice [(5.45±1.69?2.41±0.69)?m,respectively],(all p<0.05).While the above index in Y27632 group [(10.38±2.24?5.77±2.04)?m,respectively] were lower than those in asthma group(all p<0.05).Conclusion: 1.The serum level of Rock2 in asthmatic patients is significantly higher,which is closely related to the severity of asthma and helpful to detect the condition of clinical asthmatic patients.2.The levels of Rock2,MLCK and VEGF increased significantly in asthma,the airway remodeling was significantly alleviated in asthmatic mice with Y27632 intervention,Rho/ROCK signaling pathway may be involved in airway remodeling of asthma by influencing the expression of MLCK and VEGF downstream.
Keywords/Search Tags:Asthma, Airway remodeling, ROCK2, MLCK, VEGF
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