【摘要】 目的探讨转录因子GATA6基因在肺动脉高压模型肺组织中表达水平的变化。方法采用SD大鼠左肺切除,术后第7d项背部皮下注射野百合碱(MCT,60mg/kg),建立肺动脉高压(PH)模型,于术后第1、21和35d分别检测平均肺动脉压力(mPAP);右心室(RV)和左心室+室间隔(LV+S)称重,并计算RV/(LV+S)比值;测定肺小动脉中膜厚度百分比(WT%);弹力纤维染色观察肺小血管新生内膜形成情况;应用RT-PCR技术在基因水平检测转录因子GATA6mRNA在PH模型大鼠肺组织中的表达水平。结果肺组织学检查显示在PH模型组肺切除术后35d,动物右肺腺泡内小血管出现了新生内膜病变,在对照组动物没有形成新生内膜。与对照组动物比较,PH模型组动物第21、35dmPAP、RV/(LV+S)、WT%均显著增加(P<0.0001)。两组第1dmPAP、RV/(LV+S)、WT%比较,差异无统计学意义(P>0.05)。RT-PCR检测结果显示PH模型组在第21dGATA6mRNA表达开始下调,在第35d下降趋势更明显,PH模型组第35d与第1d比较,GATA6mRNA表达水平下降了约4倍。结论GATA6基因mRNA水平在肺动脉高压模型肺组织中表达下调,提示GATA6基因表达水平变化可能在PH肺血管重构中起着重要作用。更多还原

【Abstract】 Objective To investigate the expression of GATA6 gene in lung tissue of rat with pulmonary hypertension. Methods Male Sprague-Dawley rats (350 to 400 g) were received monocrotaline (MCT) (60 mg/kg) subcutaneous injection on day 7 after left lung resection. Mean pulmonary artery pressure (mPAP),right ventricle (RV)/〔left ventricle (LV)+ interventricular septum (S)〕 ratio and pulmonary artery wall thickness (WT%) were detected on day 1,21,35 after left lung resection, respectively. Neointimal formation in small pulmonary vessels was observed by Von Gienson stain. The level of expression of GATA6 mRNA in lung tissue was detected by reverse transcription polymerase chain reaction(RT-PCR). Results Neointimal changes developed in right lung intra-acinar vessels on day 35 after left lung resection (day 28 after MCT injection). Neointimal lesions did not develop in control animals. Animals treated with left lung resection plus MCT had significantly increased mPAP values on day 21〔(27.10±2.02) mmHg, 1 mmHg=133.32 Pa〕, with a further increase on day 35 (39.75±3.62) mmHg, as compared with control animals 〔(16.80±1.03) mmHg, day 21; (17.10±1.20) mmHg, day 35, P<0.0001〕. The RV/(LV+S) ratio increased from 0.266±0.015 (day 1) to 0.456±0.025 (day 21) and 0.627±0.040 (day 35), as compared with those of control animals (P<0.0001) 〔0.267±0.016 (day 1), 0.272±0.015 (day 21) and 0.257±0.019 (day 35)〕; Compared with normal pulmonary arteries, MCT injection after left lung resection resulted in severe media hypertrophy after 35 days. The level of GATA6 mRNA in rats received left lung resection plus MCT was downregulated about 4-fold on day 35, compared with that in control animals, and these tendency was observed on day 21 after left lung resection. Conclusion The expression of GATA6 gene is downregulated in neointimal model of pulmonary hypertension, it suggests that GATA6 may play a key role in pulmonary vascular remodeling.更多还原