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目的:探讨尾加压素Ⅱ受体(urotensinⅡreceptor,UT)在慢性低氧高二氧化碳肺动脉高压大鼠肺动脉中的动态变化及其意义。方法:对不同低氧(高二氧化碳)时间(1周、2周、4周)大鼠,放射性配基结合法检测肺动脉质膜UT结合位点,组织原位杂交测定各级肺小动脉UT及尾加压素Ⅱ(UⅡ)mRNA的表达。结果:①肺动脉平均压(mPAP)、右心室(RV)和左心室加室间隔(LV+S)的重量比:1周组(1HH)较对照组(NC)分别增高26.2%和21.6%、2周组(2HH)较1HH增高22.5%和14.1%、4HH组与2HH组间无显著差别(P>0.05)。②肺主动脉质膜UT最大结合位点(Bmax),1HH组比NC组高38.8%(P<0.01),2HH组比1HH组高23.2%(P<0.01),4HH组比2HH组高7.3%(P<0.05),随低氧时间延长有渐升的趋势;UⅡ受体亲和力(Kd值)各组间无差别。③三级肺小动脉UⅡmRNA相对含量的变化:2HH、4HH组明显高于NC组(P均<0.01);2HH组较1HH组分别高5.9%(P>0.05)、16.4%和9.1%(P均<0.01);4HH组与2HH组间无明显差异。④三级肺小动脉UT mRNA相对含量的变化:各低氧高二氧化碳组均高于NC组(P均<0.01),以1HH组后2级肺小动脉的表达最强,而4HH组与2HH组间无显著差别(P>0.05)。⑤肺小动脉显微结构的变化:4HH组各级血管均有显著重构,1HH组无明显变化,2HH组介于两者之间。结论:UT在慢性低氧高二氧化碳肺动脉高压大鼠肺动脉内的动态变化与肺动脉高压、肺血管改建的病理进程密切相关。
Objective: To investigate the dynamic changes of urotensin Ⅱ receptor (UT) in the pulmonary arteries of chronic hypoxia and hypercapnic pulmonary hypertension rats and its significance. Method: Different hypoxia (hypercapnia) time (1 week, 2 weeks, 4 weeks) rats, radioligand binding assay UT pulmonary membrane binding sites, levels of lung tissue in situ hybridization assay and arterioles UT Urotensin Ⅱ (U Ⅱ) mRNA expression. Results: ① mean pulmonary artery pressure (mPAP), right ventricle (RV) and left ventricle plus septum (LV + S) ratio by weight: 1 week (1HH) than the control group (NC) increased 26.2% and 21.6%, respectively, 2h group (2HH) increased by 22.5% and 14.1% compared with 1HH, 4HH group and 2HH group no significant difference (P> 0.05). (2) The maximal binding sites of UT in plasma of the pulmonary aorta were 38.8% (P <0.01) higher in 1HH group than in NC group, 23.2% (P <0.01) in 2HH group and 7.3% in 2HH group % (P <0.05), with the increase of hypoxia time, there is a trend of increase; UⅡ receptor affinity (Kd value) between the groups no difference. ③ three changes in pulmonary arterioles UⅡmRNA relative content: 2HH, 4HH group was significantly higher than NC group (P <0.01); 2HH group than 1HH group were 5.9% higher (P> 0.05), 16.4% and 9.1% (P All <0.01). There was no significant difference between 4HH group and 2HH group. (4) The relative content of UT mRNA in the three pulmonary arteries: The hypoxic hypercapnia group was higher than the NC group (all P <0.01), the expression of the second grade pulmonary arteries was the strongest in the 1HH group, No significant difference between groups (P> 0.05). ⑤The changes of microstructure of pulmonary arterioles: There were significant remodeling of blood vessels at all levels in 4HH group, no significant changes in 1HH group, and between 2HH group. CONCLUSION: The dynamic changes of UT in the pulmonary arteries of rats with chronic hypoxemic hypercapnic pulmonary hypertension are closely related to the pathological process of pulmonary hypertension and pulmonary vascular remodeling.