慢性低O_2高CO_2肺动脉高压大鼠右心室骨桥蛋白及其整合素β 3受体mRNA表达的变化

Changes of expressions of osteopontin and integrin β 3 mRNA in right ventricle of pulmonary hypertensive rats induced by hypoxia-hypercapnia

目的:观察慢性低O2高CO2肺动脉高压大鼠右心室心肌骨桥蛋白(OPN)及其整合素β3受体基因表达变化与右心室重塑的关系。方法:48只雄性SD大鼠随机分为四组:对照组(C组)、低O2高CO21w、低O2高CO22w和4w组(1HH、2HH和4HH)。除对照组吸入空气外,其他三组大鼠置于含9.0%～11.0%O2,5.5%～6.5%CO2的低O2高CO2氧舱内,每天8h,每周6d。测定平均肺动脉压(mPAP)和右心室肥厚指数;采用RT-PCR法测定不同低O2高CO2组大鼠右心室心肌骨桥蛋白(OPN)及其整合素β3受体mRNA的表达水平。结果:①低O2高CO2各组大鼠mPAP和RV/LV+S均明显高于C组(P<0.01),并且随着低O2高CO2时间的延长而增高。②C组大鼠右心室心肌OPN和整合素β3mRNA表达水平均很低,低O2高CO2各组大鼠心肌OPN和整合素β3mRNA表达水平增高,与C组比较差异均有显著性(P<0.01和P<0.05)。相关性分析显示,骨桥蛋白mRNA表达水平与大鼠右心室肥大程度呈显著正相关性(P<0.01)。结论:慢性低O2高CO2大鼠肺动脉高压及右室肥大形成过程中,右心室心肌OPN及其受体整合素β3基因表达增高,可能在右心室心肌重塑中起重要的作用。

Objetive：To investigate the changes of expressions of osteopontin （OPN） and integrin messeager RNA in right heart remodeling associated with pulmonary hypertensive rats induced by hypoxia- hypercapnia. Methods：Forty-eight male Sprague-Dawley rats （Weight： 180-220g） were randomly divided into four groups： control group（C）, hypoxic hypercapnia 1-week, 2-week and 4-week group （ 1HH, 2HH, 4HH）. All rats except the rats of group C were placed in a isobaric hypoxic hypercapnic chamber, where O2 concentration was maintained within 9.0-11.0 % and CO2 concentration was regulated within 5.5-6.5% （8 hours/day, 6 days/week）. The mean pulmonary arterial pressure（mPAP） measured with catheters, and the ratio of the weight： right ventricle /（left ventricle plus septum） was calculated. The expressions of osteopontin （OPN）and its receptor integrin β 3 messeager RNA in right ventricle were detected with RTPCR. Results：①The mean pulmonary artery pressure（mPAP） and weight ratio of right ventricle to left ventricle and septum[RV/（LV＋S）] in all hypoxic hypercapnia groups were higher than those in normal control group （P〈0.01）,respectively, and these changes in mPAP and the ratio in all hypoxic hypercapnia groups tended to up with the exposure time of hypoxic hypercapnica increasing. ②The content of OPN and integrin β3 mRNA expression in right ventricle in all hypoxic hypercapnic groups were higher than that in control group. Gonclusion：The expressions of OPN and its receptor integrin β 3 mRNA in right ventricle increase significantly during the formation of pulmonary hypertension and right ventricle hypertrophy in rats chronically exposed to hypexia-hypercapnia. These changes indicate that OPN and integrin β 3 may be involved in right ventricle remodeling.