Yuan Li-Xing, Liu Han-Min, Li Mi, Gao Ju, Zhou Tong-Fu
Department of Pediatrics, West China Second Hospital, Sichuan University, Chengdu 610041, China.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2005 Sep;36(5):668-71.
To study the expression of heme oxygenase-1 mRNA and pulmonary remodeling before and after surgical establishment of left-to-right shunt in volume-overloaded SD rats and rats with Losartan intervention.
Left-to-right shunt volume-overloaded SD rat models were established by aortocaval shunt operation. Seven rats with shunt were placed on Losartan (Losartan group), 7 rats with but not given Losartan were included in the operation group, and 4 rats after sham operation served as controls. Pulmonary pressure and right ventricular pressure were measured during catheterization. The relative weights ventricles were determined after execution of the rats. Pulmonary vascular remodeling parameters, including percentage arterial wall thickness and percentage muscularized small arteries, were assessed by morphometry. Heme oxygenase-1 (HO-1) mRNA expression and heme oxygenase-2 (HO-2) mRNA expression were detected RT-PCR method.
Pulmonary artery pressure and right ventricular relative weight decreased significantly in the rats of Losartan group; in addition, the percentage arterial wall thickness and percentage of muscularized small arteries in the Losartan group were reduced as compared with those in the operation group. The level 1 mRAN expression in rats with shunt was significantly higher than that in rats without shunt. The level mRNA expression in the Losartan group decreased remarkably as compared against that in the operation The level of HO-1 mRNA expression in lungs was significantly higher than that in ventricles. There statistically significant differences in HO-2 mRNA expression levels between the three rat groups.
Losartan intervention can markedly reduce pulmonary pressure, inhibit vascular remodeling in volume-overloaded left-to-right shunt rats, and result in down-regulation of HO-1 mRNA expression.
研究容量负荷过重的左向右分流SD大鼠及经氯沙坦干预的大鼠在手术建立左向右分流前后血红素加氧酶-1 mRNA的表达及肺重塑情况。
通过主动脉腔静脉分流术建立左向右分流容量负荷过重的SD大鼠模型。7只分流大鼠给予氯沙坦(氯沙坦组),7只分流但未给予氯沙坦的大鼠纳入手术组,4只假手术大鼠作为对照组。插管时测量肺动脉压和右心室压。处死大鼠后测定心室相对重量。通过形态计量学评估肺血管重塑参数,包括动脉壁厚度百分比和肌化小动脉百分比。采用逆转录聚合酶链反应(RT-PCR)法检测血红素加氧酶-1(HO-1)mRNA表达和血红素加氧酶-2(HO-2)mRNA表达。
氯沙坦组大鼠肺动脉压和右心室相对重量显著降低;此外,与手术组相比,氯沙坦组动脉壁厚度百分比和肌化小动脉百分比降低。分流大鼠的HO-1 mRNA表达水平显著高于未分流大鼠。与手术组相比,氯沙坦组mRNA表达水平显著降低。肺组织中HO-1 mRNA表达水平显著高于心室。三组大鼠HO-2 mRNA表达水平差异有统计学意义。
氯沙坦干预可显著降低肺动脉压,抑制容量负荷过重的左向右分流大鼠的血管重塑,并导致HO-1 mRNA表达下调。