缺氧性肺动脉高压大鼠尾加压素Ⅱ、一氧化氮和C型利钠肽的表达及意义

The expression and significance of urotensin Ⅱ,nitric oxide,and C-type natriuretic peptide in hypoxia-induced pulmonary hypertension in rats

目的检测缺氧性肺动脉高压(HPH)大鼠血浆和肺匀浆中尾加压素(U-Ⅱ)、一氧化氮(NO)和C型利钠肽(CNP)的变化,探讨氧疗及这些因子在HPH中的作用。方法雄性W istar大鼠30只均分为对照组、缺氧组、氧疗组。测定各组平均体动脉压(mSAP)、肺动脉平均压(mPAP)、右室肥厚指数(RVH I),血浆U-Ⅱ、NO、CNP水平,肺匀浆U-Ⅱ、CNP水平,光镜观察肺动脉结构改变,扫描电镜观察肺小动脉超微结构。结果缺氧组大鼠mPAP、RVH I[(34.1±2.8)mm Hg、0.43±0.11]显著高于对照组[(18.9±2.0)mm Hg、0.28±0.04,P均<0.01],血浆U-Ⅱ、NO、CNP[(4.4±0.9)pg/m l、(20.8±7.0)μmol/L、(6.6±1.2)pg/m l]均显著高于对照组[(0.9±0.4)pg/m l、(13.2±2.0)μmol/L、(4.0±0.6)pg/m l,P均<0.01],肺匀浆U-Ⅱ、CNP[(6.3±0.5)、(1.89±0.43)pg/m l]亦显著高于对照组[(2.6±0.5)、(0.69±0.21)pg/m l,P均<0.01]。氧疗组大鼠mPAP,血浆U-Ⅱ、NO、CNP,肺匀浆U-Ⅱ、CNP分别为(31.4±2.0)mm Hg,(2.1±0.7)pg/m l、(14.8±1.7)μmol/L、(4.4±0.7)pg/m l,(3.5±0.8)pg/m l、(0.74±0.17)pg/m l;与缺氧组比较差异均有统计学意义(P均<0.01),而RVH I差异无统计学意义(P>0.05)。光镜和电镜下,氧疗组肺血管形态学改变较缺氧组轻。结论缺氧导致HPH形成,U-Ⅱ、NO和CNP参与HPH的病理生理过程,这些因子之间比值失衡可能是导致HPH发生发展的因素之一。

Objective To investigate the alteration of plasma and lung tissue homogenate urotensin Ⅱ （ U- Ⅱ ）, nitric oxide （NO） and C-type natriuretic peptide （CNP） levels in rats with hypoxia-induced pulmonary hypertension （HPH） and to study the role of these factors and oxygen treatment in the development of HPH. Methods Thirty male Wistar rats were randomly divided into three groups：a control group, a group with hypoxia for 14 days and a group with oxygen treatment after hypoxia for 14 days, 10 rats per group. Mean pulmonary arterial pressure（ mPAP）, mean systematic arterial pressure（mSAP） and right ventrical hypertrophy index （RVHI） were measured. The plasma levels of U- Ⅱ , NO, CNP, and the lung tissue homogenate levels of U-Ⅱ and CNP were measured. The structure of the pulmonary arteries was examined using optical microscope. The microstructure and ultrastructure changes in pulmonary small arteries were examined using electron microscope. Results The mPAP and RVHI in the hypoxia group [ （34. 1 ±2. 8）mm Hg,0. 43 ±0. 11 ] were higher than those in the control group[ （ 18.9 ± 2. 0） mm Hg, 0. 28 ± 0. 04, all P 〈 0. 01 ]. The plasma levels of U- Ⅱ , NO, and CNP [ （ 4. 4 ± 0. 9 ） pg/ml, （ 20. 8 ± 7.0 ） μmol/L, （6. 6 ± 1.2 ） pg/ml ] , and the lung tissue homogenate levels of U- Ⅱ and CNP [ （ 6. 3 ± 0. 5 ）, （1.89 ± 0. 43 ）pg/ml ] in the hypoxia group were higher than those in the control group [ （0. 9 ± 0.4 ） pg/ml,（13.2 ± 2.0） μmol/L, （4.0 ± 0.6） pg/ml, （2.6 ± 0.5） pg/ml, （0.69 ± 0.21） pg/ml, respectively, all P 〈 0. 01 ]. Compared with the hypoxia group, the mPAP, the plasma levels of U- Ⅱ, NO, and CNP, and the lung tissue homogenate levels of U-Ⅱ and CNP in the oxygen treatment group [ （31.4 ± 2. 0 ） mmHg,（2.1±0.7） pg/ml,（14.8＋1.7） μmol/L,（4.4±0.7） pg/ml;（3.5 ±0.8） pg/ml,（0.74± 0. 17） pg/ml,respectively] were significantly decreased（ all P 〈 0. 01 ）. The pulmonary vessel morphology changes of the oxygen treatment group were ameliorated. Conclusions U- Ⅱ, NO and CNP are involved in the pathophysiologic process of HPH. Imbalance of these factors may be partially responsible for the development of the disease.