染料木黄酮对大鼠慢性栓塞性肺动脉高压的减缓作用及其机制  

Attenuation of chronic thromboembolic pulmonary hypertension in rats with genistein and relevant mechanism

作　　者：张玉坤[1] 王导新[1] 李长毅[1] 

机构地区：[1]重庆医科大学附属第二医院呼吸内科,重庆400010

出　　处：《中国生物制品学杂志》2012年第3期333-335,339,共4页Chinese Journal of Biologicals

基　　金：国家自然科学基金资助(30971303)

摘　　要：目的研究染料木黄酮对大鼠慢性栓塞性肺动脉高压(Chronic thromboembolic pulmonary hypertension,CTEPH)的减缓作用及对肺组织一氧化氮合酶(Endothelial nitric oxide synthase,eNOS)水平的影响,并探讨其可能的机制。方法雄性SD大鼠麻醉后,经颈静脉回输体外制备的自体血栓栓子,2周后同法进行二次栓塞,将造模成功的大鼠分为染料木黄酮治疗组、栓塞4周组和8周组。全程腹腔注射抗纤维溶解剂氨甲环酸,达目标日期后,采用右心导管法检测平均肺动脉压;开胸取心肺组织,心脏左右心室、室间隔分别称重后,计算右心室肥厚指数,电镜下观察肺小动脉结构变化;Western blot法检测肺组织中eNOS水平。结果染料木黄酮治疗组及栓塞8周组大鼠平均肺动脉压及右心室肥厚指数较栓塞4周组明显升高(P均<0.01),染料木黄酮组较栓塞8周组显著降低(P<0.01);染料木黄酮治疗组及栓塞8周组大鼠肺小动脉结构重塑(平滑肌细胞明显增殖);染料木黄酮治疗组大鼠肺组织中eNOS水平较栓塞4周和8周组明显升高(P<0.01)。结论染料木黄酮能减缓大鼠慢性栓塞性肺动脉高压的进展,其机制可能与其上调eNOS的水平有关。Objective To investigate the attenuation of chronic thromboembolic pulmonary hypertension（CTEPH） in rats with genistein,the effect of genistein on endothelial nitric oxide synthase（eNOS） level in lung tissue,as well as the relevant mechanism.Methods Male SD rats were narcotized then injected i.v.twice with autologous thrombi prepared in vitro,at an interval of 2 weeks to establish the rat model of pulmonary thromboembolism（PTE）.The model rats were divided into one test and two model control groups,and injected i.p.with tranexamic acid,an antifibrinolytic reagent once a day.The rats in model control groups 1 and 2 were raised for 4 and 8 weeks after PTE respectively,while those in test group were injected s.c.with genistein at a dosage of 40 μg / kg 4 weeks after PTE,once a day for 4 weeks.All the rats were determined for mean pulmonary artery pressure（mPAP） on the target dates by right cardiac atheterzation then killed,and their heart and lung tissues were taken out and weighed for left and right cardiac ventricles as well as ventricular septal,based on which right ventricular hypertrophy index（RVHI） was calculated.The structural change of pulmonary arteriole was observed by electron microscopy,and the eNOS level in lung tissue was determined by Western blot.Results Both the mPAP and RVHI were significantly higher in test group and model control group 2 than in model control group 1（each P 0.01）,while significantly lower in test group than in model control group 2（P 0.01）.Pulmonary vascular remodeling was observed in both test group and model control group 2,expressed as significant proliferation of smooth muscle cells.However,the eNOS level in lung tissue of rats in test group was significantly higher than those in model control groups 1 and 2（P 0.01）.Conclusion Genistein attenuated the progress of CTEPH in rats,of which the mechanism might be associated with up-regulation of eNOS level.

关 键 词：肺栓塞 慢性栓塞性肺动脉高压 染料木黄酮 一氧化氮合酶 

分 类 号：R282[医药卫生—中药学] R543.1[医药卫生—中医学]