知母宁对低氧高二氧化碳大鼠TXA_2,PGI_2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

作　　者：黄晓颖[1,2] 徐晓梅[2] 王良兴[2] 李明[3] 

机构地区：[1]浙江中医药大学第一临床学院,杭州310053 [2]温州医学院附属一医呼吸内科,温州325003 [3]三九集团医药研究所,深圳518029

出　　处：《中国新药杂志》2008年第20期1761-1763,共3页Chinese Journal of New Drugs

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)

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8h，每周6d，连续4周。知母宁组大鼠每次缺O2前0．5h腹腔内注射知母宁3．3mg·kg^-1末次给药后次日，测定血浆TXA，和PGl2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-ket0-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。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 8 h of hypoxic （ inspired O2 fraction = 8.5% - 11% ） or hypereapnic （inspired CO2 fraction = 5.5% - 6.5% ） ventilation for 4 weeks （6 days in one week）. Chimonin （3.3 mg· kg^- 1 ） was intraperitoneally injected 30 rain 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, ehimonin markedly reduced the increased mPAP, pulmonary arteriole micromorphometrie index [ vessel wall area/iota] area （WA/TA） ], density ,,f 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 indueed by chronic hypoxia/hypercapnia in rats, which may be due to inhibiting the synthesis of TXA2 and maintaining the balance of TXA2/PGI2.

关 键 词：知母宁 肺动脉高压 血栓素A2 前列环素 

分 类 号：R285.5[医药卫生—中药学] R286.4[医药卫生—中医学]