The Therapeutic Effect Of Mesenchymal Stem Cells On Airway Remodeling In A Asthma Model Of Rat And Its Mechanism

Objective:To observe the effect of mesenchymal stem cells(MSCs)on epithelial-mesenchymal transition(EMT)and investigate the therapeutic effect of MSCs on airway remodeling in asthma and its possible mechanism.Methods:Forty rats were divided into 4 groups: A.Control,B.Model,C.MSCs,D.Budesonide.The rats of group B,C and D were sensitized by intraperitoneal(i.p.)injection of 10% OVA suspension on days 1 and 8.Starting on day 15,the rats were challenged by inhaling 1% OVA daily for eight successive weeks(20 min each time).The group C rats were given an tail vein injection of MSCs 0.2ml(1×106cell/mL)on days 35,45,and 55 half an hour befor each OVA exposure.The group D rats were given 2mg budesonide aerosol inhalation two hours before each OVA exposure.The rats of group A received 0.9%NaCl instead of OVA on the same schedule of group B.Pathology changes of airway remodeling were detected by HE staining.Computer graphics software were used to detect airway remodeling.The concentration of transforming growth factor-beta(TGF-?1)were measured by ELISA.The expressions of E-cadherin,?-SMA and Fn were measured by SABC.Results:The thickness of airway wall and smooth muscle of group B rats were remarkably thicker than group A [(42.36±1.50,21.01±0.10)vs(25.69±0.27,14.97±0.13)?m].The levels of TGF-?1 in both BALF and serum of group B rats were remarkably higher than group A [(21.01±0.18,70.97±0.23)vs(1.14±0.19,23.05±0.16)?g/L)].The expression of E-cadherin of group B rats was remarkably lower than group A [(0.256±0.087)vs(0.469±0.012)],while the expression of ?-SMA and Fn were remarkably higher [(0.521±0.030),(0.527±0.022)vs(0.371±0.007),(0.387±0.020)](all P <0.01).The thickness of airway wall and smooth muscle of group C and D rats were 32.40±2.50 ?m,35.86±0.55 ?m and 15.71±0.89 ?m,18.72±0.89 ?m respectively.The levels of TGF-?1 in both BALF and serum of group C and D rats were 3.53±0.43 ug/L,3.25±0.25 ug/L and 31.07±0.89 ug/L,32.08±0.18 ug/L respectively.They were remarkably lower than group B(all P<0.01).The expressions of ?-SMA,Fn of group C and D rats were significantly lower than group B [(0.438±0.057),(0.445±0.027)and(0.459±0.041),(0.458±0.029)],while the expression of E-cadherin [(0.308±0.023),(0.296±0.010)] was remarkably higher group B(all P<0.01).Conclusion:1.TGF-?1 induced EMT is one of the mechanism of asthmatic airway remodeling.2.MSCs alleviate asthmatic airway remodeling by inhibiting TGF-?1 induced EMT.