葛根素对缺氧性大鼠肺组织骨桥蛋白及其整合素β3受体基因表达的影响

Effects of puerarin on expression of osteopontin and integrin β3 mRNA in lungs of rats induced by hypoxic hypercapnia

目的观察葛根素对低O2高CO2肺动脉高压大鼠肺组织骨桥蛋白及其整合素β3受体基因表达的影响。方法♂SD大鼠36只,随机分为3组,每组12只:①对照组(A组);②低O2高CO24wk组(B组);③低O2高CO24wk+葛根素组(C组)。采用右心导管法分别检测肺动脉平均压(mPAP)及颈动脉压(mCAP)。光镜观察并测量肺小动脉管壁厚度、肺细小动脉中膜平滑肌细胞核密度及中膜厚度等;采用RT-PCR检测肺组织骨桥蛋白和整合素β3mRNA表达水平。结果①B组mPAP和RV/(LV+S)均高于A组(P<0.01),而C组mPAP、RV/LV+S明显低于B组(P<0.01);②与A组大鼠相比较,B组大鼠的肺细小动脉管壁面积/管总面积(WA/TA),肺细小动脉中膜平滑肌细胞核密度(SMC),肺细小动脉中膜厚度(PAMT)均明显增高(P<均0.01);C组大鼠的WA/TA、SMC和PAMT指标均明显低于B组(P<0.01);③与A组比较B组大鼠肺组织OPN与整合素β3表达水平均明显增高(P<0.01);C组大鼠肺组织OPN表达水平明显低于B组(P<0.01),而整合素β3表达水平则与B组比较差异无显著性(P>0.05)。结论慢性低O2高CO2诱导肺动脉高压形成及血管重建过程中可能与肺组织高表达OPN及其整合素β3受体有关;而葛根素减低慢性肺动脉高压可能主要通过抑制OPN的表达而发挥作用,与整合素β3受体表达水平无关。

Aim To investigate the effects of puerarin on expression of osteopontin （OPN）and integrin β3 messeager RNA in lungs of rats induced by hypoxia-hypercapnia. Methods Thrity-six male Sprague-Dawley rats （weight： 180 - 220 g） were randomly divided into three groups ： normal control group （A） , hypoxic hypercapnia 4-week group （ B ） and hypoxic hypercapnia 4-week treated with puerarin （ C ） （ n = 12 in each group）. The mean pulmonary arterial pressure（mPAP） and mean carotid arterial pressure （mCAP）were measured respectively through the right jugular vein and left carotid artery by catheters. The changes of structure in pulmonary arterioles were observed under light microscope. The expression of osteopontin （OPN）and its receptor integrin β3 messeager RNA in lungs were detected by RT-PCR. Results （1） The mean pulmonary artery pressure（mPAP） and weight ratio of fight ventricle to left ventricle and septum [ RV/（ LV ＋ S） ] in group B were higher than those of normal control group （P 〈 0.01）, and these changes in mPAP and the ratio in group C were decreased than those in group B （P 〈 0. 01 ） ;（2） The SMC, WA/TA and the PAMT were significantly higher in group B than in group A （P 〈 0. 01）;and those in group C were significantly decreased than in group B （P 〈0. 01 ） ;（3）The content of OPN and integrin β3 mRNA expression in lungs of group B were higher than in group A（P 〈0. 01 ） ; OPN mRNA in group C was significantly lower than that in group B, but integrin β3 mRNA was not significantly different between group B and C （ P 〉 0. 05 ）. Conclusions The expression of OPN and its receptor integrin β3 mRNA in lungs increases significantly during the formation of pulmonary hypertension and vascular remodeling in rats chronically exposed to hypoxia-hypercapnia. These changes indicate that OPN and integrin β3 might be involved in pulmonary vascular remodeling; puerarin can inhibit pulmonary hypertension and has some protective effect on pulmonary vascular remodeling induced by chronic hypoxic hypercapnia, which may be related with inhibiting the expression of OPN mRNA,not with integrin β3 mRNA.