Effects of bone marrow mesenchymal stem cell transplantation on expression of transforming growth factor-β1 and tumor necrosis factor-α level of emphysema rats

Abstract

Objective By research the expression of TGF-β1 and TNF-αlevel in lung tissue and serum after transplantation of bone marrow mesenchymal stem cells(BMSCs) to emphysema rats,study the effects of BMSCs on airway inflammation and remodeling of emphysema rats. Methods Thirty-six healthy male SD rats were randomly divided into control group, simple emphysema and BMSCs transplantation group.Rat models of emphysema were established by exposure to chronic tobacco smoke with reference to Xu Sanlin chronic smoke exposure device,six months later,the BMSCs suspension was infused into the tail vein of BMSCs translation group rats,and the equal amount of PBS buffer was infused into the control group.The relevant indices were measured after BMSCs transplantation,the pathology changes of lung tissue were observed,and the mean linear intercept(MLI),mean alveoli number(MAN) and total area of the tube wall(WAt)/wall inside the perimeter(Pi) were calculated after HE staining, the levels of TGF-β1 and TNF-αin lung tissue and serumwere detected by ELISA kits,the TGF-β1 expression of airway epithelial cells was measured by immunohistochemical method. Results ①The microscopic morphology change:pure emphysema and BMSCs transplantation group both have different degrees of emphysema pathological changes,the latter is significantly lighter than the former.②The MLI (177±22.14)μm and WAt/Pi(193.05±53.91)μm in the simple emphysema group were obviously higher than that of control group[(95±44.28)μm and(78.39±26.51)μm,all P< 0.05).The TNF-α [(14.47±5.85)and(92.07±23.73)] ng/L and TGF-β1[(66.77±9.91) and(72.92±4.96)]μg/L levels in lung tissue and serum and the TGF-β1 average optical density value of the positive particle in airway epithelial cell(6.44±2.40)×10-2 of the simple emphysema group were obviously higher than that of control group[(5.17±2.57)and(53.49±15.47) ng/L,(49.02±9.91)and(59.36±6.89)μg/L and(3.83±1.81)×10-2,all P<0.05],the MAN(92.73±28.93)/mm2 was obviously lower than that of control group[(190.84±57.49)/mm2,P<0.05)].The MLI(131±37.55)μm and WAt/Pi(121.62± 34.94)μm in the BMSCs transplantation group were obviously higher than that of control group.The TNF-α[(9.60±5.06)and(70.92±15.16) ng/L],TGF-β1[(57.44±4.78) and(66.43±6.70)]μg/L levels in lung tissue and serum and the TGF-β1 average optical density value of the positive particle in airway epithelial cell(4.28±1.23)×10-2 in the BMSCs transplantation group were obviously higher than that of control group(P< 0.05),the MAN(146.73±49.12)/mm2 was obviously lower than that of control group(P< 0.05),while the BMSCs transplantation group were obviously lower than simple emphysema(P< 0.05).③In each group rats,the lung tissue and serum TGF-β1 level correlated positively with TNF-αlevel(r= 0.556, P= 0.001)and WAt(r= 0.702, P< 0.01).The lung tissue and serum TNF-αlevel correlated positively with MLI(r= 0.578,P= 0.001) and WAt(r= 0.440, P= 0.015),and correlated negatively with MAN(r=-0.439,P= 0.015).WAt was positively correlated with MLI(r= 0.398, P= 0.029),and negatively correlated with MAN(r=-0.475, P= 0.008). Conclusions Transplantation of BMSCs can reduce the TGF-β1 and TNF-αlevels in lung tissue and serum of emphysema rat,then reduce airway inflammation and remodeling,and thus improve the severity of emphysema. Key words: Emphysema rat; Bone marrow mesenchymal stem cells; Transforming growth factor-β1; Tumor necrosis factor-α