NO前体对高肺血流时肺动脉胱硫醚-γ-裂解酶基因表达的调节作用

REGULATION OF ENDOGENOUS CYSTATHIONINE-γ-LYASE GENE EXPRESSION IN HIGH PULMONARY FLOW BY NITRIC OXIDE PRECURSOR

目的:研究一氧化氮(NO)前体L-精氨酸(L-Arg)对高肺血流时肺动脉胱硫醚-γ-裂解酶(内源性硫化氢生成酶)的调节作用,以探讨NO体系对高肺血流肺动脉高压及肺血管结构重建调节作用的机制。方法:30只雄性SD大鼠随机分为对照组,分流组和分流+L-Arg组。对后两组大鼠行腹主动脉-下腔静脉分流术。观察术后11周大鼠肺动脉平均压(mPAP)、右心室肥厚和肺动脉相对中膜面积的改变,用竞争逆转录聚合酶链反应(RT-PCR)对肺组织CSEmRNA表达进行定量分析,同时用化学法测定肺组织硫化氢产出率。结果:分流组大鼠mPAP及肺动脉相对中膜面积明显高于对照组(P<0.01),而分流+L-Arg组大鼠mPAP及肺动脉相对中膜面积明显低于分流组(P<0.01)。分流组CSEmRNA表达与对照组相比明显降低(P<0.01),而分流组+L-Arg组CSEmRNA表达又明显高于分流组(P<0.05);分流组大鼠肺组织硫化氢产出率明显低于对照组(P<0.01),而分流组+L-Arg组大鼠肺组织硫化氢产出率及血浆硫化氢含量明显高于分流组(P<0.01)。结论:高肺血流可致肺动脉CSEmRNA下调,外源性NO能够缓解CSEmRNA的改变,从而对高肺血流所致肺血管结构重建和肺动脉高压起调节作用。

Aim： Pulmonary hypertension is a common complication of congenital heart disease with a left-to right shunt. The mechanism of pulmonary hypertension induced by high pulmonary blood flow is still not fully understood. Recent studies showed that hydrogen sulfide （H2S） could relax vascular smooth muscle cells. But the change of the system of H2S in pulmonary hypertension induced by high pulmonary blood flow was not reported. We studied the influence on expression of CSEmRNA and production of hydrogen sulfide in rat lung tissues by L-Arginine, in order to demonstrate a regulating role of nitric oxide（NO）in the regulation of cystathionine-γ-lyase/ hydrogen sulfide system（CSE/H2S）. Methods： Thirty male SD rats were randomly divided into shunting group, shunting with L- Arginine group, and control group. Abdominal aorta and inferior vena cava shunting was produced in rats of the later group. Pulmonary artery mean pressure （mPAP） and the hypertrophy of right ventricle of each rat were analyzed. The expression of lung tissue CSEmRNA was measured using quantitative reverse transcription-polymerase chain reaction and in situ hybridization. The activity of CSE in lung tissue was measured according to chemical analysis. Results： mPAP was significantly increased in shunted rats compared with normal control（ P 〈 0.01 ）, the expression of lung tissue CSEmRNA and the activity of CSE in lung tissue were decreased in shunt group（P 〈 0.01）. However, L-arginine significantly attenuated pulmonary artery pressure, but augmented the expression of lung tissue CSEmRNA as well as the activity of CSE in lung tissue. Conclusion： L-Arginine reverses the down-regulation of CSE/H2S system in high pulmonary blood flow-induced pulmonary hypertension.