胸交感神经阻滞降低大鼠低氧性肺动脉高压的机制  

Mechanism of thoracic sympathetic blockade reducing hypoxic pulmonary arterial hypertension in rats

作　　者：于世寰[1] 刘凤岐[2] 张春玲[1] 鲁犇 王立峰[3] 孙文广[4] 路伟娜[1] YU Shi-huan;LIU Feng-qi;ZHANG Chun-ling(Department of Pulmonary Disease,The First Hospital of Harbin Medical University,Haerbin Heilongjiang 150001,China;Department of Heart Disease,The First Hospital of Harbin Medical University,Haerbin Heilongjiang 150001,China)

机构地区：[1]哈尔滨医科大学附属第一医院呼吸内科,黑龙江哈尔滨150001 [2]哈尔滨医科大学附属第一医院心内科,黑龙江哈尔滨150001 [3]哈尔滨医科大学附属第一医院病理科,黑龙江哈尔滨150001 [4]哈尔滨医科大学附属第一医院营养咨询科,黑龙江哈尔滨150001

出　　处：《临床和实验医学杂志》2019年第7期680-683,共4页Journal of Clinical and Experimental Medicine

基　　金：黑龙江省自然科学基金项目(面上项目)(编号:D201217)

摘　　要：目的研究胸交感神经阻滞(TSB)降低大鼠低氧性肺动脉高压(HPH)的机制。方法选择健康雄性Wistar大鼠48只,随机分为常氧组、低氧组、低氧/罗哌卡因组、低氧/生理盐水组各12只。常氧组在常氧常压下饲养3周,其余3组大鼠在自制常压低氧(10±0.5)%舱内饲养3周,同时低氧/罗哌卡因组和低氧/生理盐水组给与胸段硬膜外腔置管分别注入0.2%罗哌卡因和0.9%生理盐水各50μl行胸段(胸1-5)交感神经阻滞术(TSB)。用放射免疫分析法测定大鼠血清环磷酸鸟苷(cGMP)和血清肿瘤坏死因子α(TNF-α)含量; RT-PCR和蛋白印迹法测定大鼠肺组织c AMP反应元件结合蛋白(CREB)的基因表达和蛋白质表达。结果①低氧/罗哌卡因组大鼠血浆cGMP水平增加和血清TNF-α水平降低,与低氧组、低氧/生理盐水组比较差异显著。②低氧/罗哌卡因组大鼠肺小动脉血管CREB的基因表达和蛋白质表达均降低,而低氧组、低氧/生理盐水组表达增加。结论 TSB可降低HPH大鼠血清TNF-α水平,升高血浆cGMP水平。同时能逆转肺小动脉CREB的基因和蛋白质过表达现象,这可能是TSB降低HPH和改善血管重构重要的分子学机制之一。Objective The present study was aimed to investigate the mechanism of thoracic sympathetic blockade(TSB)in hypoxia-induced pulmonary hypertension(HPH)in rats.Methods Forty eight Wistar rats were randomly divided into 4 groups of twelve,namely normoxia,hypoxia,hypoxia/ropivacaine and hypoxia/saline.Animals were placed in a hypoxia chamber and instrumented with epidural catheters at the thoracic level.Rats were injected with saline or ropivacaine.Serum cGMP and TNF-αwere measured using radioimmuno assay.Real-time PCR and Western boltting were employed to examine the expression of cAMP responding-element binding protein(CREB).Results We found that significantly hypoxia-induced rats increased in levels of serum cGMP and TNF-αwas reversed by TSB.Moreover,hypoxia increased expression of CREB at mRNA and protein levels and TSB suppressed the elevated expression of CREB.Conclusion TSB can reduce serum level of TNF-αand increase cGMP.The treatment can reverse upregulated expression of CREB at mRNA and protein production.

关 键 词：大鼠 低氧性肺动脉高压 胸交感神经阻滞 肿瘤坏死因子Α 环磷酸鸟苷 CAMP反应元件结合蛋白 

分 类 号：R544.1[医药卫生—心血管疾病]