肾上腺髓质素缓解大鼠低氧性肺动脉高压

目的探讨肾上腺髓质素(ADM)对大鼠低氧性肺动脉高压的防治作用及机制。方法雄性Wistar大鼠18只,分为对照组、低氧组和低氧 ADM组,每组6只。持续皮下注射ADM1-50后,测定平均肺动脉压(mPAP)、右心室肥大指数RV/(LV S)、肺小动脉病理及形态计量学和体循环平均压(mSBP),放免法测定肺动脉血浆ADM水平,原位杂交测定肺动脉ADMR mRNA的表达。结果①低氧组大鼠mPAP,RV/(LV S),管壁厚度与血管外径比值(MT%)及管壁面积与血管面积比值(MA%)均显著升高(P<0.01);ADM组显著缓解以上变化(P<0.01)。②低氧组与低氧 ADM组肺动脉血浆ADM浓度均高于对照组,且低氧 ADM组较低氧组ADM浓度低(P<0.05)。③低氧组与低氧 ADM组的ADMR mRNA表达较对照组增强(P<0.01)。结论持续皮下注射ADM对慢性低氧所致的肺动脉高压及肺血管重塑有预防和部分逆转作用。

Adrenomedullin relieves the pulmonary hypertension in hypoxic rats

Objective To investigate the effects and mechanisms of adrenomedullin (ADM) and adrenomedullin receptor (ADMR) on hypoxia pulmonary hypertension (HPH) in rats.Methods Eighteen male Wistar rats were randomly divided into three groups:control group, hypoxic group and hypoxic plus ADM group.ADM was subcutaneously administered into rats with ADM. After 21 days, The mean pulmonary arterial pressure (mPAP) and right ventricular hypertrophy index[RV/(LV S)] were measured. Hypoxic pulmonary vascular remodeling(HPSR) was observed with morphometric analysis. The level of pulmonary arterial plasma ADM was measured by radioimmunoassay. The semiquantitate in situ hybridization was used to measure the expression of ADMR mRNA in pulmonary artery walls. Results (1) The level of mPAP, RV/(LV S),the ratio of vascular wall thick ness to external diameter(MT%) and ratio of vascular wall area to total area (MA%) were significantly higher in hypoxia group than those in control group(2) The pulmonary artery plasma ADM level was significantly higher in hypoxic group and hypoxic plus ADM group than that in control group(P<0.01), and the ADM level decreased in rat of hypoxicplus ADM group compared with hypoxic group(P<0.05).(3) ADMR mRNA expressed more in pulmonary artery walls of hypoxia group and hypoxic plus ADM group(P<0.01).Conclusion ADM may partly prevent the development of HPH and pulmonary vascular remodling. Exogenous ADM has no negative feedback effect on pulmonary arterial plasma ADM and ADMR mRNA.