摘要
目的观察肾上腺髓质素(adrenomedullin,ADM)治疗对慢性低氧性肺动脉高压大鼠血流动力学指标、肺血管重构及细胞因子表达的影响,探讨ADM对慢性低氧性肺动脉高压的作用及其可能机制。方法 30只雄性Wistar大鼠随机分为对照组(n=10),低氧组(n=10)和治疗组(n=10)。治疗组大鼠通过微量渗透泵皮下持续给予ADM(300 ng/h)2周,低氧组大鼠则用同样的方法给予200μl生理盐水注入。低氧2周后,以右心导管法测定大鼠血流动力学指标,放射免疫法检测血清中醛固酮及ADM水平。处死大鼠,检测右心室与左心室加室间隔比值[RV/(LV+S)]。将肺组织切片进行HE染色,图像分析检测肺血管重构。Western印迹检测重塑的肺血管中转化生长因子-β1(TGF-β1)、内皮素-1(ET-1)及肿瘤坏死因子α(TNF-α)的表达。结果低氧2周后,与对照组大鼠相比,低氧组大鼠肺动脉收缩压(PASP)、肺动脉舒张压(PADP)、平均肺动脉压(mPAP)及血清醛固酮水平显著升高,RV/(LV+S)显著增加,肺血管管壁厚度与外径的比值(MT%)及管壁面积与血管总面积的比值(MA%)显著增加,重塑的肺血管中TGF-β1、ET-1和TNF-α的表达显著增加;与低氧组大鼠相比,治疗组大鼠PASP、PADP、mPAP、血清醛固酮水平显著降低,RV/(LV+S)及重塑的肺血管中MT%和MA%显著下降,同时,重塑的肺血管中TGF-β1、ET-1和TNF-α表达显著降低。结论外源性补充ADM可改善低氧性肺动脉高压大鼠的血流动力学指标及肺血管重构,其机制可能和降低醛固酮水平,抑制肺动脉TGF-β1、ET-1和TNF-α的表达有关。
Objective To investigate the effect of adrenomedullin （ADM） on hemodynamic indexes, pulmonary vascu- lar structural remodeling and cytokines in rats with hypoxic pulmonary hypertension （PH）, and to study the effect of ADM on chronic hypoxic PH and its possible mechanism. Methods Thirty rats were randomly divided into three groups ： normal control （n = 10）, hypoxia （n = 10） and ADM-treated hypoxia （n=10）. ADM was subcutaneously administered into rats of the ADM-treated hypoxia group by a mini-osmotic pump （300 ng/h） for two weeks. After two weeks of hypoxic chal- lenge, indexes of hemodynamics were calculated. Aldosterone and human ADM levels in rat serum were measured by radio- immunoassay before the rats were sacrificed and the ratio of the RV weight to LV plus septum weight [ RV/（ LV ＋ S） ] was calculated for assessment of right ventricular hypertrophy. Histological sections of the lungs were stained with hematoxylin- eosin （HE） and pulmonary arterioles were studied using a computerized image analyzer. The ratio of vessel wall thickness to pulmonary artery diameter （ MT% ） and the ratio of vessel wall area to total area （ MA% ） were calculated. Meanwhile, the expression of transforming growth factor （TGF）-β1, endothelin-1 （ET-1） and tumor necrosis factor（TNF-α） in pulmonary arteries were detected by Western blotting. Results The pulmonary artery systolic pressure （PASP）, pulmonary artery di- astolic pressure （PADP）, mean pulmonary artery pressure （mPAP）, RV/（ LV ＋ S ）, MT% and MA% increased obviously in the hypoxia group compared with normal controls. The levels of serum aldosterone and the protein expression levels of TGF-β1 , ET-1 and TNF-α of pulmonary arteries in the hypoxia group were increased more significantly than in the control group. PASP, PADP, mPAP and RV1 （ LV ＋ S） were significantly reduced in the ADM-treated hypoxia group compared with those in the hypoxia group. ADM markedly reduced MT% and MA% of hypoxic rats, with a decrease in the levels of serum aldosterone and expression of TGF-β1, ET-1 and TNF-α. Conclusion ADM might play a regulatory role in the development of hypoxic pulmonary hypertension and hypoxic pulmonary vascular remodeling by decreasing the levels of ser- um aldosterone and inhibiting the expression of TGF-β1, ET-1 and TNF-α.
出处
《军事医学》
CAS
CSCD
北大核心
2013年第12期887-891,共5页
Military Medical Sciences
基金
山西省基础研究计划项目(2012011040-3
2013011049-4)
山西高校科技研究开发项目(20101150)
长治市科技计划项目(20123060)
