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红细胞增多对大鼠低氧肺动脉高压及其肺血管重构的影响

Effect of Polycythemia on Hypoxia Induced Pulmonary Hypertension and Pulmonary Vascular Remodeling in Rats

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【作者】 周艳荣周同甫欧珠罗布乔莉娜王晓琴许红波刘瀚旻华益民

【Author】 ZHOU Yan-rong,ZHOU Tong-fu,OUZHULUOBU,QIAO Li-na,WANG Xiao-qin,XU Hong-bo, LIU Han-ming,HUA Yi-min. Department of Pediatric Cardiology,West China Second Hospital,Sichuan University,Chengdu 610041,China

【机构】 四川大学华西第二医院小儿心血管科西藏大学医学院外科教研室

【摘要】 目的探讨实验性红细胞增多对大鼠低氧性肺动脉高压及其肺血管重构的影响。方法健康SD大鼠随机分为:常氧对照组(C)、单纯低氧组(H)、低氧+不同剂量的人重组促红细胞生成素(rEPO)组。除对照组外各低氧组大鼠共缺氧21d,每日8h。rEPO组每周腹部皮下注射不同剂量的rEPO(300U/kg、600U/kg、900U/kg、1200U/kg)3次。取血样测定红细胞数(RBC)、血红蛋白(Hb)、红细胞压积(Hct)、血浆EPO浓度、全血/血浆黏度;颈外静脉插管测定平均肺动脉压力(mPAP);动物处死后计算右心室/(左心室+室间隔)〔RV/(LV+S)〕评价右室肥厚程度;光镜观察肺小动脉管壁厚度百分比、肺非肌性小动脉肌化程度。结果①随着rEPO注射剂量的增加,血浆EPO浓度相应的增加,同时RBC、Hb、Hct、全血及血浆黏度亦有不同程度的增高;②高、低切变率下的全血黏度与Hct均呈正相关,mPAP与高切变率下的全血黏度呈直线相关;③随着rEPO剂量的增加,反映肺动脉高压程度的mPAP逐渐增高,但是肺血管重构及右室肥厚程度反而有所缓解。结论外源性EPO诱导的红细胞增多通过增高全血黏度使肺血管的血流阻力增加,从而促使低氧性肺动脉高压形成,但却减轻了右室肥厚及肺血管重构程度,后者可能系机体对缺氧的一种代偿机制。尽管如此,EPO和/或红细胞增多的净结果仍然是使肺动脉高压加重。

【Abstract】 Objective To investigate the effect of polycythemia on hypoxia induced pulmonary hypertension and pulmonary vascular remodeling in rats. Methods The healthy female Sprague-Dawley rats were randomly divided into 3 groups:normoxia control group (C group),hypoxia group (H group),hypoxia + different doses of human recombine hemopoietin (rEPO) group. All rats in hyoxia groups were exposed to hypoxia,8 hours every day,for 21 days. The rEPO groups were injected sc with different doses of rEPO (300 U/kg,600 U/kg,900 U/kg,1200 U/kg) thrice weekly. Blood samples were taken for the measurement of RBC,Hb,Hct,plasma EPO concentration,whole blood / plasma viscosities,the animals were then catheterized to record mean pulmonary arterial pressure (mPAP) and demised to calculate the ratio〔RV/(LV+S)〕. Percentage of vascular wall thickness and muscularization of non-muscular pulmonary arteriole were examined microscopically. Results ①As the dosage of exogenous rEPO increased,blood concentration of EPO increased correspondingly,as RBC,Hb,Hct and whole blood/ plasma viscosities increased in various degrees.② There was positive correlation between whole blood viscosity and Hct at both high and low shears and linear correlation between mPAP and whole blood viscosity at high shear. ③The degree of pulmonary hypertension,reflected by mPAP increased in accordance to rEPO dosage increment. However,the extent of pulmonary vascular remodeling alleviated somehow as the rEPO dose increased and so did right ventricular hypertrophy. Conclusion Polycythemia induced by exogenous EPO increases the blood viscosity and the pulmonary vascular resistance,which contributes to the formation of hypoxia induced pulmonary hypertension.

【基金】 纽约中华医学基金会(CMB-06838)资助
  • 【文献出处】 四川大学学报(医学版) ,Journal of Sichuan University(Medical Science Edition) , 编辑部邮箱 ,2009年04期
  • 【分类号】R541.5
  • 【被引频次】10
  • 【下载频次】194
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