摘要
目的 探讨高肺血流所致肺血管结构重建时内源性一氧化氮 (NO)体系的变化。方法对大鼠行腹主动脉 下腔静脉分流术。 11周后以右心导管法测定肺动脉平均压 (mPAP) ,检测右心室 /左心室 +室间隔 [RV/(LV +S) ]的比值。观测肺血管显微及超微结构的变化 ,并且以分光光度计测定血浆NO含量 ,分别以原位杂交和免疫组织化学的方法检测肺动脉内皮型NO合酶 (eNOS)mRNA和蛋白的表达。结果 分流组大鼠mPAP明显高于对照组 [分别为 (2 2 5± 2 6)mmHg、(15 8± 2 8)mmHg,1mmHg =0 13 3kPa ,P <0 0 1],RV/(LV +S)比值也明显增加。光镜下 ,肺小血管肌化程度明显增强 ,肺中、小型肌型动脉相对中膜厚度明显增加。电镜下 ,肺腺泡内动脉内皮细胞增生、变性 ,内弹力层粗细不均 ,平滑肌细胞肥厚、向合成表型转化。并且分流组大鼠血浆NO含量明显高于对照组 [分别 (为3 0 2± 7 9) μmol/L、(19 7± 5 7) μmol/L ,P <0 0 1],肺动脉eNOSmRNA和蛋白表达均明显增强。 结论 NO体系 eNOSmRNA表达。
Objective Pulmonary vascular structural remodeling induced by high pulmonary blood flow is an important pathologic basis of pulmonary hypertension with congenital heart disease of left to right shunt However, the mechanism is still not clear The present study aimed to examine the alteration of endogenous nitric oxide (NO) pathway in high pulmonary blood flow induced pulmonary vascular structural remodeling, so as to explore the role of NO pathway in pulmonary hypertension induced by high pulmonary blood flow Methods Sixteen male SD rats were randomly divided into control group ( n =8) and shunting group ( n =8) Aortocaval shunting was produced for 11 weeks in shunt rats Pulmonary artery mean pressure (mPAP) of each rat was evaluated using right cardiac catheterization The ratio of right ventricular mass to left ventricular plus septal mass was detected Pulmonary vascular micro and ultra structure was examined by using a light microscope and a transmitted electronic microscope Meanwhile, the concentration of plasma NO was measured by spectrophotometry The expressions of endothelial NO synthase (eNOS) mRNA and protein by pulmonary arteries were detected by in situ hybridization and immunohistochemistry, respectively Results After 11 week aortocaval shunting, mPAP was significantly increased [(22 5±2 6) mmHg vs. (15 8±2 8) mmHg, 1 mmHg=0 133 kPa, t = 4 97, P <0 01], and RV/(LV+S) was also markedly increased(0 267±0 022 vs. 0 221±0 016, t = 4 85, P <0 01) The percentage of muscularized arteries was obviously increased in shunt rats compared with controls [(23 2±2 4)% vs. (13 5±2 1)%, t = 7 82, P <0 01], and relative medial thickness of pulmonary arteries was obviously increased in shunt rats [median pulmonary artery:(7 76±0 56) % vs? (4 82±1 03)%, t =6 23, P <0 01;small pulmonary artery:(11 94±0 66)% vs. (6 91±0 53)%, t = 14 96, P <0 01] Ultrastructural changes, such as hyperplasia and degeneration of endothelial cells, irregularity of internal elastic laminar and hypertrophy and the increased number of synthetic phenotype of smooth muscle cells, were found in intrapulmonary arteries of shunt rats Meanwhile, plasma NO concentration was increased [(30 2±7 9) μmol/L vs (19 7±5 7) μmol/L, t =3 05, P <0 01) and eNOS mRNA and protein expressions by pulmonary arteries were significantly augmented in rats of shunting group [WTHZ]Conclusion The upregulation of eNOS/NO might be an adaptive response of pulmonary circulation to an increased blood flow in the development of pulmonary hypertension and pulmonary vascular structural remodeling
出处
《中华儿科杂志》
CAS
CSCD
北大核心
2003年第3期215-218,共4页
Chinese Journal of Pediatrics
基金
国家重点基础研究发展规划资助项目(G2 0 0 0 0 5 690 5 )
北京大学生物医学跨学科研究项目
关键词
高肺血流
肺血管结构重建
内源性一氧化氮
肺性高血压
Nitric oxide
Hypertension, pulmonary
Vascular surgical procedures Pulmonary artery
Nitric oxide synthase
