缬沙坦对哮喘小鼠气道重构及结缔组织生长因子表达的影响

Effect of valsartan on asthma mice's airway remodelling and CTGF expression

目的观察缬沙坦对哮喘小鼠早期气道重构和结缔组织生长因子(CTGF)在气道内表达的影响。方法 40只小鼠随机分为正常对照组、哮喘模型组、地塞米松组(2 mg/kg)、缬沙坦组(50mg/kg)4组,卵清蛋白致敏建立哮喘模型。肺组织切片行苏木精-伊红和Masson染色以测定平滑肌面积、基底膜胶原面积;RT-PCR检测结缔组织生长因子CTGFmRNA,免疫印迹和免疫组织化学方法检测其蛋白表达水平及组织细胞定位。结果平滑肌面积和胶原沉积面积哮喘模型组显著高于正常对照组,地塞米松组和缬沙坦组均显著低于哮喘模型组(P<0.01);CTGF mRNA灰度值和Western bloting蛋白相对表达量哮喘模型组显著高于正常对照组,地塞米松组和缬沙坦组均显著低于哮喘模型组(P<0.01)。CTGF蛋白表达水平与平滑肌面积、胶原沉积面积均呈正相关(r分别为0.602和0.579,P<0.01)。结论缬沙坦具有抑制哮喘气道重构的作用,其机制可能与其下调气道内CTGF表达相关。

Objective To observe the influence of valstartan on airway remodelling and connective tissue growth factor(CTGF) expression in airway of mouse model of asthma.Methods Forty BALB/C mice were divided into 4 groups:normal control group,asthmatic model group, dexamethasone group(2 mg/kg),valstartan group(50 mg/kg).The mouse model of asthma was established by ovalbumin intraperitoneal injection and aerosolization.Dexamethasone group and valstartan group were given different treatments.The lung tissue slices were stained with Hematoxylin-eosin and Masson for analyzing the smooth muscle area and airway wall collagen area.The transcription level of CTGF was measured by reverse transcriptase-polymerase chain reaction to determine the level of its mRNA,and western bloting and immunohistochemistry were used to detect its protein expression and location.Results In these four groups,the area of bronchial smooth muscle and the area of collagen deposition were significantly higher in asthmatic model group than in control group(P &lt;0.01),but remarkably lower in dexamethasone group and valstartan group than in model group(all P &lt;0.01).The relative potency of mRNA and protein expression of model group was increased,as compared with control(P &lt;0.01);dexamethasone group’s and valstartan group’s were decreased,as compared with model(P &lt;0.01).The protein expression level of CTGF was positively correlated with the area of bronchial smooth muscle and with the area of collagen deposition(r=0.602,0.579 respectively,P &lt; 0.01).Conclusion The valsartan can inhibit airway remodelling in asthmatic mice and it may be correlated with the down regulation of CTGF in airway.