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知母宁对低氧高二氧化碳大鼠TXA2,PGI2及肺动脉高压的影响

Effect of chimonin on pulmonary arterial pressure,and thromboxane A2 and prostacyclin after chronic hypoxia/hypercapnia in rats

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【作者】 黄晓颖徐晓梅王良兴李明

【Author】 HUANG Xiao-ying1,2,XU Xiao-mei2,WANG Liang-xing2,LI Ming3(1 First Clinical Academy of Zhejiang Chinese Medical University,Hangzhou 310053,China;2 Department of Respiration,First Hospital of Wenzhou Medical College,Wenzhou 325003,China;3 Institute of Biochemistry,Shenzhen 999 Corporation,Shenzhe 518029,China)

【机构】 浙江中医药大学第一临床学院温州医学院附属一医呼吸内科三九集团医药研究所

【摘要】 目的:研究知母宁对慢性低氧高二氧化碳大鼠血栓素A2(TXA2)、前列环素(PGI2)、肺动脉压力及肺血管结构重建的影响。方法:36只SD大鼠随机分为正常对照组,肺动脉高压模型组和知母宁组,每组12只。后2组大鼠每天在低氧(8.5%~11%)高CO2(5.5%~6.5%)环境中放置8 h,每周6 d,连续4周。知母宁组大鼠每次缺O2前0.5 h腹腔内注射知母宁3.3 mg.kg-1。末次给药后次日,测定血浆TXA2和PGI2的稳定的代谢产物TXB2和6-keto-PGF1α的浓度,测定肺动脉平均压(mPAP),并观察肺细小动脉显微结构。结果:知母宁组mPAP显著低于模型组(P<0.01),肺细小动脉显微结构改变较模型组也显著降低(P<0.01)。知母宁组血浆TXB2和TXB2/6-keto-PGF1α比值均显著低于模型组(P<0.01),但6-keto-PGF1α含量则无显著改变(P>0.05)。结论:知母宁对低氧高二氧化碳致肺动脉高压大鼠具有明显的保护作用,其作用机制可能与抑制TXA2合成、减轻TXA2/PGI2的平衡失调有关。

【Abstract】 Objective:To determine the effect of chimonin on pulmonary arterial pressure,pulmonary vessel remodeling,thromboxane A2 and prostacyclin after chronic hypoxia/hypercapnia in rats.Methods: Thirty-six Sprague-Dawley rats were randomly divided into three groups.Rats were subjected to 8h of hypoxic(inspired O2 fraction=8.5%~11%) or hypercapnic(inspired CO2 fraction=5.5%~6.5%) ventilation for 4 weeks(6 days in one week).Chimonin(3.3mg·kg-1) was intraperitoneally injected 30 min before hypoxic ventilation.Following the last dose,plasma thromboxane B2(TXB2) and 6-keto-PGF1α(the stable metabolites of thromboxane A2 and prostacyclin),mean pulmonary artery pressure(mPAP),and pulmonary arteriole micromorphometric index were measured.Results: After chronic hypoxia/hypercapnia,chimonin markedly reduced the increased mPAP,pulmonary arteriole micromorphometric index [vessel wall area/total area(WA/TA)],density of cell nucleus of medial smooth muscle cell(SMC),and the thickness medial smooth muscle cell layer(PAMT,P<0.01).Chimonin also reduced the increased plasma level of TXB2 and the ratio of TXB2/6-keto-PGF1α,but did not affect the level of 6-keto-PGF1α.Conclusions: Chimonin can prevent pulmonary artery hypertension and pulmonary vessel remodeling induced by chronic hypoxia/hypercapnia in rats,which may be due to inhibiting the synthesis of TXA2 and maintaining the balance of TXA2/PGI2.

【基金】 浙江省自然科学基金资助项目(M303617);浙江省教育厅资助项目(20030719)
  • 【文献出处】 中国新药杂志 ,Chinese Journal of New Drugs , 编辑部邮箱 ,2008年20期
  • 【分类号】R285.5
  • 【被引频次】4
  • 【下载频次】148
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