TGF-β1/Smads通路在哮喘气道重塑中的表达及意义
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摘要
为了探讨TGF-β1/Smads通路在哮喘气道重塑中的表达及意义,本研究选取清洁级雄性SD大鼠40只,将大鼠随机分为4组,正常对照组,哮喘2周组,哮喘4周组和哮喘8周组,每组10只。其中哮喘2周组、哮喘4周组和哮喘8组大鼠制作哮喘模型,分别在激发哮喘2周、4周和8周后处死,采用HE染色观察各组气道重塑,同时测量气道形态学参数,采用免疫组化染色检测TGF-β1、Smad2和Smad7蛋白表达。结果表明与哮喘2周组和哮喘4周组相比,哮喘8周组气道支气管壁周围有大量细胞浸润,气道平滑肌增厚,管腔狭窄;哮喘各组总管壁面积、内壁面积和平滑肌面积均明显高于正常对照组(p<0.05),其中哮喘8周组总管壁面积、内壁面积和平滑肌面积分别为(42.26±1.61)μm~2、(34.40±1.22)μm~2和(8.22±1.12)μm2,明显高于哮喘2周组和哮喘4周组(p<0.05);哮喘8周组TGF-β1和Smad2蛋白表达分别为1.562±0.122和1.613±0.121,明显高于哮喘2周组和哮喘4周组(p<0.05),而Smad7蛋白表达为0.251±0.081,明显低于哮喘2周组和哮喘4周组(p<0.05)。本研究初步推测TGF-β1/Smads通路在哮喘气道重塑中有重要作用,其中TGF-β1和Smads可能有促进气道重塑的作用,而Smad7可能有抑制气道重塑作用,值得进一步研究。
To investigate the expression and significance of TGF-β1/Smads pathway in airway remodeling of asthma, this research chose 40 male SD rats as experimental materials. The rats were randomly divided into 4 groups,the normal control group, the asthma 2 weeks group, the asthma 4 weeks group and the asthma 8 weeks group, with10 rats in each group. The asthma model was made in the 2 week asthma group, while the 4 week asthma group and the 8 week asthma group were killed after 2, 4 and 8 weeks of asthma; This study observed airway remodeling by HE staining, and measured airway morphology. The protein expression of TGF-β1, Smad2 and Smad7 protein were analyzed by immunohistochemical staining. The results showed that there were a large number of cell infiltration around the bronchial wall, thickening of the airway smooth muscle and narrowing of the lumen in the asthma 8 week group compared to asthma 2 weeks group and asthma 4 weeks group; The total tube wall area, inner wall area and smooth muscle area of the each asthma group were significantly higher than those of the normal control group(p<0.05); Total tube wall area, inner wall area and smooth muscle area of asthma 8 week group were tested(42.26±1.61) μm2,(34.40±1.22) μm~2 and(8.22±1.12) μm~2, were significantly higher than those of asthma 2 weeks group and asthma 4 weeks group(p<0.05); The protein expression of TGF-β1 and Smad2 in asthma 8 weeks group were(1.562±0.122) and(1.613±0.121), were significantly higher than those in asthma 2 weeks group and asthma 4 weeks group p<0.05),while the expression of Smad7 was(0.251±0.081), were significantly lower than that of asthma 2 weeks group and asthma 4 weeks group(p<0.05). We had a primarily conclusion that TGF-β1/Smads pathway might play an important role in airway remodeling in asthma, of which the TGF-β1 and Smads might promote airway remodeling,while Smad7 might inhibit airway remodeling, which might be worthy for further study.
To investigate the expression and significance of TGF-β1/Smads pathway in airway remodeling of asthma, this research chose 40 male SD rats as experimental materials. The rats were randomly divided into 4 groups,the normal control group, the asthma 2 weeks group, the asthma 4 weeks group and the asthma 8 weeks group, with10 rats in each group. The asthma model was made in the 2 week asthma group, while the 4 week asthma group and the 8 week asthma group were killed after 2, 4 and 8 weeks of asthma; This study observed airway remodeling by HE staining, and measured airway morphology. The protein expression of TGF-β1, Smad2 and Smad7 protein were analyzed by immunohistochemical staining. The results showed that there were a large number of cell infiltration around the bronchial wall, thickening of the airway smooth muscle and narrowing of the lumen in the asthma 8 week group compared to asthma 2 weeks group and asthma 4 weeks group; The total tube wall area, inner wall area and smooth muscle area of the each asthma group were significantly higher than those of the normal control group(p<0.05); Total tube wall area, inner wall area and smooth muscle area of asthma 8 week group were tested(42.26±1.61) μm2,(34.40±1.22) μm~2 and(8.22±1.12) μm~2, were significantly higher than those of asthma 2 weeks group and asthma 4 weeks group(p<0.05); The protein expression of TGF-β1 and Smad2 in asthma 8 weeks group were(1.562±0.122) and(1.613±0.121), were significantly higher than those in asthma 2 weeks group and asthma 4 weeks group p<0.05),while the expression of Smad7 was(0.251±0.081), were significantly lower than that of asthma 2 weeks group and asthma 4 weeks group(p<0.05). We had a primarily conclusion that TGF-β1/Smads pathway might play an important role in airway remodeling in asthma, of which the TGF-β1 and Smads might promote airway remodeling,while Smad7 might inhibit airway remodeling, which might be worthy for further study.
引文
Liu J.Y.,Liu D.S.,Liu Z.F.,and Han B.,2015,Effect of PGD2on TGF-β1/Smads signaling pathway in mouse lung fibroblasts,Shandong Yiyao(Shandong Medical Journal),55(9):5-8(刘建英,刘代顺,刘振峰,韩冰,2015,PGD2对小鼠肺成纤维细胞TGF-β1/Smads信号通路的影响,山东医药,55(9):5-8)
Nader M.A.,2015,Inhibition of airway inflammation and remodeling by sitagliptin in murine chronic asthma,Int.Immunopharmacol.,29(2):761-769
Noble P.B.,Pascoe C.D.,Lan B.,Ito S.,Kistemaker L.E.,Tatler A.L.,Pera T.,Brook B.S.,Gosens R.,and West A.R.,2014,Airway smooth muscle in asthma:Linking contraction and mechanotransduction to disease pathogenesis and remodeling,Pulm.Pharmacol.Ther.,29(2):96-107
Sobko E.A.,Solov'Eva I.A.,Kraposhina A.,Riazanova N.G.,Vtiurina S.S.,Salmina A.B.,and Demko I.B.,2014,Relationship between endothelial dysfunction and mechanisms of systemic inflammation in left heart remodeling in patients with bronchial asthma,Klin.Med.(Mosk),92(11):43-48
Wang H.,and Shao Y.X.,2017,Relationship between expression of TGF-β1 levels and airway remodeling of asthma,Harbin Yike Daxue Xuebao(Journal of Harbin Medical University),51(4):330-333(王浩,邵玉霞,2017,TGF-β1的表达水平与哮喘患者气道重塑的关系,哈尔滨医科大学学报,51(4):330-333)
Witt C.A.,Sheshadri A.,Carlstrom L.,Tarsi J.,Kozlowski J.,Wilson B.,Gierada D.S.,Hoffman E.,Fain S.B.,CookGranroth J.,Sajol G.,Sierra O.,Giri T.,O'Neill M.,Zheng J.,Schechtman K.B.,Bacharier L.B.,Jarjour N.,Busse W.,Castro M.,and NHLBI Severe Asthma Research Program(SARP),2014,Longitudinal changes in airway remodeling and air trapping in severe asthma,Academic Radiology,21(8):986-993
Nader M.A.,2015,Inhibition of airway inflammation and remodeling by sitagliptin in murine chronic asthma,Int.Immunopharmacol.,29(2):761-769
Noble P.B.,Pascoe C.D.,Lan B.,Ito S.,Kistemaker L.E.,Tatler A.L.,Pera T.,Brook B.S.,Gosens R.,and West A.R.,2014,Airway smooth muscle in asthma:Linking contraction and mechanotransduction to disease pathogenesis and remodeling,Pulm.Pharmacol.Ther.,29(2):96-107
Sobko E.A.,Solov'Eva I.A.,Kraposhina A.,Riazanova N.G.,Vtiurina S.S.,Salmina A.B.,and Demko I.B.,2014,Relationship between endothelial dysfunction and mechanisms of systemic inflammation in left heart remodeling in patients with bronchial asthma,Klin.Med.(Mosk),92(11):43-48
Wang H.,and Shao Y.X.,2017,Relationship between expression of TGF-β1 levels and airway remodeling of asthma,Harbin Yike Daxue Xuebao(Journal of Harbin Medical University),51(4):330-333(王浩,邵玉霞,2017,TGF-β1的表达水平与哮喘患者气道重塑的关系,哈尔滨医科大学学报,51(4):330-333)
Witt C.A.,Sheshadri A.,Carlstrom L.,Tarsi J.,Kozlowski J.,Wilson B.,Gierada D.S.,Hoffman E.,Fain S.B.,CookGranroth J.,Sajol G.,Sierra O.,Giri T.,O'Neill M.,Zheng J.,Schechtman K.B.,Bacharier L.B.,Jarjour N.,Busse W.,Castro M.,and NHLBI Severe Asthma Research Program(SARP),2014,Longitudinal changes in airway remodeling and air trapping in severe asthma,Academic Radiology,21(8):986-993